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Sample records for spontaneous lymphocyte proliferation

  1. Spontaneous T Cell Proliferation: A Physiologic Process to Create and Maintain Homeostatic Balance and Diversity of the Immune System

    Science.gov (United States)

    Min, Booki

    2018-01-01

    Naive T lymphocytes undergo heterogeneous proliferative responses when introduced into lymphopenic hosts, referred to as “homeostatic proliferation” and “spontaneous proliferation.” Spontaneous proliferation is a unique process through which the immune system generates memory phenotype cells with increasing T cell receptors repertoire complexity. Here, the mechanisms that initiate and control spontaneous proliferation are discussed. PMID:29616038

  2. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

    Forell, B.; Myers, L.S. Jr.; Norman, A.

    1979-01-01

    The rate of spontaneous unscheduled DNA synthesis in human lymphocytes was estimated from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. The contribution of scheduled DNA synthesis to the observed incorporation was reduced by inhibiting replication with hydroxyurea and by separating freshly replicated single-stranded DNA (ss-DNA) from repaired ds-DNA by column chromatography. The residual contribution of scheduled DNA synthesis was estimated by observing effects on thymidine incorporation of: (a) increasing the rate of production of apurinic sites, and alternatively, (b) increasing the number of cells in S-phase. Corrections based on estimates of endogenous pool size were also made. The rate of spontaneous unscheduled DNA synthesis is estimated to be 490 +- 120 thymidine molecules incorporated per cell per hour. These results compare favorably with estimates made from rates of depurination and depyrimidination of DNA, measured in molecular systems if we assume thymidine is incorporated by a short patch mechanism which incorporates an average of four bases per lesion

  3. Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

    Science.gov (United States)

    Hu, Z Q; Murakami, K; Ikigai, H; Shimamura, T

    1992-03-01

    Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

  4. Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis

    International Nuclear Information System (INIS)

    Chorostowska-Wynimko, J.; Kleniewska, D.; Sokolnicka, I.; Rogala, E.; Skopinska-Rozewska, E.

    1995-01-01

    Lymphocytes play a central regulatory role in mechanisms contributing to impaired function of immune system in atopy. The aim of our study was evaluate the mitogen-induced proliferation of lymphocytes in a group of asymptomatic, seasonal allergic rhinitis patients. A highly significant lower mitogen-induced proliferation and, in contrast to other studies, significantly lower background proliferative activity of lymphocytes were found in the atopic persons, comparing to the controls. We concluded that the decreased mitogen-induced proliferation of lymphocytes observed in allergic patients reflects abnormal T cell function, which is due to the atopic status, and not only as it was believed to the antigen-induced lymphocyte activation. (author). 26 refs, 1 tab

  5. Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis

    Energy Technology Data Exchange (ETDEWEB)

    Chorostowska-Wynimko, J.; Kleniewska, D.; Sokolnicka, I.; Rogala, E.; Skopinska-Rozewska, E. [Dept. of Immunology. Institute of Tuberculosis and Lung Diseases, Warsaw (Poland)

    1995-12-31

    Lymphocytes play a central regulatory role in mechanisms contributing to impaired function of immune system in atopy. The aim of our study was evaluate the mitogen-induced proliferation of lymphocytes in a group of asymptomatic, seasonal allergic rhinitis patients. A highly significant lower mitogen-induced proliferation and, in contrast to other studies, significantly lower background proliferative activity of lymphocytes were found in the atopic persons, comparing to the controls. We concluded that the decreased mitogen-induced proliferation of lymphocytes observed in allergic patients reflects abnormal T cell function, which is due to the atopic status, and not only as it was believed to the antigen-induced lymphocyte activation. (author). 26 refs, 1 tab.

  6. 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...

  7. Cell proliferation and radiosensitivity of cow lymphocytes in culture

    International Nuclear Information System (INIS)

    Modave, C.; Fabry, L.; Leonard, A.

    1982-01-01

    The harlequin-staining technique has been used to study, after PHA-stimulation, the cell proliferation of cow lymphocytes in culture and to assess the radiosensitivity in first mitosis cells. At the 48 h fixation time, only 34% of the cells are in first mitosis whereas 55% are already in second and 11% in third mitosis. The exposure of cow lymphocytes to 200 rad X-rays result in the production of 16% dicentric chromosomes in first mitosis cells [fr

  8. Stretched cell cycle model for proliferating lymphocytes

    Science.gov (United States)

    Dowling, Mark R.; Kan, Andrey; Heinzel, Susanne; Zhou, Jie H. S.; Marchingo, Julia M.; Wellard, Cameron J.; Markham, John F.; Hodgkin, Philip D.

    2014-01-01

    Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G1 phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G2/M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics. PMID:24733943

  9. Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

    Directory of Open Access Journals (Sweden)

    Khadijeh Khosravi

    2016-05-01

    Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

  10. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increase...

  11. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A

    1998-01-01

    cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions....

  12. [Spontaneous pregnancy in a patient with lymphocytic hypophysitis].

    Science.gov (United States)

    Dong, Ai-mei; Yin, Hong-fang; Gao, Yan-ming; Guo, Xiao-hui

    2009-04-18

    Lymphocytic hypophysitis(LH) is a rare but increasingly recognized autoimmune endocrine condition that causes partial or total hypopituitarism and is often associated with peripartum young women. We here report a 28-year-old patient who had a spontaneous and uneventful pregnancy following LH that had been treated with transspenoidal surgery and followed by anti-inflammatory agent. The woman failed to lactate and developed frontal headaches 3 months after normal delivery of her first child 3 years ago. Lab test showed the reduced concentrations of thyroxine, estradial and cortisol, suggesting hypopituitarism. Magnetic resonance imaging of the brain with contrast was performed and showed a uniformly enhancing pituitary mass with elevated optic chiasm. She underwent transsphenoidal surgery and histological examination of the resected specimen was consistent with lymphocytic hypophysitis. Anti-inflamation was started with prednisolone 40 mg per day because of a recurrence of headache that had completely recovered after surgery and regularly withdrawn to a long term maintenance dose of 10 mg per day. Physiological thyroxine replacement therapy was maintained. Her menstruation was restored without sex hormone replacement after 3 months. Three years after surgery, she got pregnant spontaneously and had normal breastfeeding after delivery. LH did not recur during this peripartum.

  13. Isolation of human spontaneous killer lymphocytes by bacterial adherence.

    Science.gov (United States)

    Kleinman, R; De Boer, K P; Teodorescu, M

    1980-01-01

    Human lymphocyte subpopulations (B, T1, T2, T3, and T4 our denomination) have been identified previously by bacterial adherence and differences between them in mitogen responses and specific cytotoxic activity have been found. In this study another aspect has been investigated in order to find functions associated with these subpopulations, namely the spontaneous killing (SK) ability. Freshly isolated human peripheral blood lymphocytes (PBL) were separated into adherent and non-adherent cells following centrifugation against various bact:rial monolayers. The PBL and the resulting subpopulations of PBL were tested alone or in combination as effector cells in a 4 hr cytotoxicity assay against human lymphoblastoid cel- lines of B or T cell origin. The T3 + T4 cells or T4 cells alone showed a significantly higher SK activity against both B and T target cell lines when compared with unseparated PBL, T1 + T2, or T3 cells alone. Whe Fc portion of IgG, contain the lymphocytes responsible for SK activity and that SK cells can be purified by negative selection using bacterial adherence. PMID:7389207

  14. DMPD: Induction of proliferation and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11090938 Induction of proliferation and cytokine production in human T lymphocytes ... (.png) (.svg) (.html) (.csml) Show Induction of proliferation and cytokine production in human T lymphocyte...s bylipopolysaccharide (LPS). PubmedID 11090938 Title Induction of proliferation

  15. Effect of thapsigargin on cytoplasmic Ca2+ and proliferation of human lymphocytes in relation to AIDS

    DEFF Research Database (Denmark)

    Scharff, O; Foder, B; Thastrup, Ole

    1988-01-01

    the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production...... response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas...... on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation....

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Rosalina Tossige-Gomes

    Full Text Available 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

  18. Early expression of nucleolar SURF-6 protein in mouse spleen lymphocytes activated for proliferation in vitro.

    Science.gov (United States)

    Moraleva, A A; Malysheva, M V; Magoulas, Ch; Polzikov, M A; Zatsepina, O V

    2009-05-01

    Using specific antibodies we studied the content of nucleolar SURF-6 protein, which participates in rRNA processing, in mouser spleen lymphocytes activated for proliferation with concanavalin A and compared it with the content of nucleolar nucleophosmin/B23 protein and DNA replication factor PCNA, well-known markers of proliferating cells. Using immunocytochemistry and immunoblotting methods we demonstrate that the concentration of all these proteins increases simultaneously with increasing the proportion of proliferating cells. Unlike nucleophosmin/B23, SURF-6 protein was not revealed in quiescent lymphocyte nucleoli, while the increase of its level in activated lymphocytes preceded elevation of PCNA level. These observations suggest that nucleolar protein SURF-6 can act as a marker of early T lymphocyte activation for proliferation and that it could participate in cell cycle regulation in mammals.

  19. Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Odum, Niels; Theander, T G

    1986-01-01

    . Sulphadoxine (SDX), added in vitro, had no effect on the lymphocytes, while SDX plus PYR had the same effect as PYR alone. Oral intake of SDX plus PYR (Fansidar) also blocked the thymidine synthesis of mitogen-stimulated lymphocytes. The possible consequences of the findings for the use of PYR in malaria...

  20. l-Arginine modulates neonatal lymphocyte proliferation through an interleukin-2 independent pathway

    Science.gov (United States)

    Yu, Hong-Ren; Kuo, Ho-Chang; Huang, Li-Tung; Chen, Chih-Cheng; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Huang, Hsin-Chun; Yang, Kuender D; Ou, Chia-Yo; Hsu, Te-Yao

    2014-01-01

    In cases of arginine depletion, lymphocyte proliferation, cytokine production and CD3ζ chain expression are all diminished. In addition to myeloid suppressor cells, polymorphonuclear cells (PMN) also exert T-cell immune suppressive effects through arginase-induced l-arginine depletion, especially during pregnancy. In this study, we investigated how arginase/l-arginine modulates neonatal lymphocyte proliferation. Results showed that the neonatal plasma l-arginine level was lower than in adults (48·1 ± 11·3 versus 86·5 ± 14·6 μm; P = 0·003). Neonatal PMN had a greater abundance of arginase I protein than adult PMN. Both transcriptional regulation and post-transcriptional regulation were responsible for the higher arginase I expression of neonatal PMN. Exogenous l-arginine enhanced neonate lymphocyte proliferation but not that of adult cells. The RNA-binding protein HuR was important but was not the only modulation factor in l-arginine-regulated neonatal T-cell proliferation. l-Arginine-mediated neonatal lymphocyte proliferation could not be blocked by interleukin-2 receptor blocking antibodies. These results suggest that the altered arginase/l-arginine cascade may be one of the mechanisms that contribute to altered neonatal immune responses. Exogenous l-arginine could enhance neonate lymphocyte proliferation through an interleukin-2-independent pathway. PMID:24697328

  1. Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ. Medical Center, Maywood, IL (United States); Chang-Liu, Chin-Mei [Argonne National Lab., IL (United States); Chung, Jen; Libertin, C.R. [Loyola Univ. Medical Center, Maywood, IL (United States)

    1993-09-01

    Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.

  2. The effect of deoxyguanosine on human lymphocyte function. I. Analysis of the interference with lymphocyte proliferation in vitro.

    Science.gov (United States)

    Spaapen, L J; Rijkers, G T; Staal, G E; Rijksen, G; Wadman, S K; Stoop, J W; Zegers, B J

    1984-05-01

    The effect of deoxyguanosine on mitogen- and antigen-induced proliferation of peripheral blood lymphocytes from healthy donors was studied. Deoxyguanosine was found to inhibit the proliferative response to mitogens and antigens. Concentrations of deoxyguanosine causing 50% inhibition of the proliferation proved to be dependent on the activity of catabolic enzymes, such as purine nucleoside phosphorylase (PNP), in sera used in the culture media. The inhibitory effect of deoxyguanosine on phytohemagglutinin (PHA)-induced cell proliferation was prevented by deoxycytidine as well as by hypoxanthine. These findings were analyzed further by determination of intracellular (deoxy)-nucleotide levels. Stimulation of lymphocytes by PHA in the presence of deoxyguanosine leads to intracellular accumulation of dGTP. The presence of hypoxanthine in addition to deoxyguanosine abolished the inhibitory effect but did not prevent dGTP accumulation. On the other hand, the addition of deoxycytidine in combination with deoxyguanosine did not lead to intracellular accumulation of detectable amounts of dGTP, but only gave partial protection against the toxic effect. Furthermore, guanosine inhibited mitogen-induced cell proliferation to the same extent as did deoxyguanosine provided that the culture media were supplemented with pretreated fetal calf serum. Peripheral blood lymphocytes of a PNP-deficient or a HGPRT-deficient patient in cultures stimulated with PHA or pokeweed mitogen were resistant to the inhibitory effects of guanosine and were less sensitive to deoxyguanosine than cells of normal donors. The present results clearly show the involvement of two pathways contributing to deoxyguanosine-mediated inhibition of the proliferation of normal lymphocytes, i.e., on the one hand degradation of deoxyguanosine by PNP, salvage of guanine by HGPRT, and (possibly) phosphorylation of GMP eventually leading to GTP, and on the other hand formation of dGTP by direct phosphorylation of

  3. 3-Methylcholanthrene inhibits lymphocyte proliferation and increases intracellular calcium levels in common carp (Cyprinus carpio L)

    International Nuclear Information System (INIS)

    Reynaud, S.; Duchiron, C.; Deschaux, P.

    2003-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. Many authors have focused on macrophage activities in fish exposed to PAHs. However, fewer studies have reported decrease in specific immunity in such fish. We investigated the intracellular mechanisms by which the 3-methylcholanthrene (3-MC) decreased lymphocyte proliferation in carp. T- and B-lymphocyte proliferation induced by Concanavalin A (Con A) and lipopolysaccharide (LPS) were inhibited by 3-MC (0.5-50 μM). 3-MC also produced a rapid and a sustained increase in intracellular calcium concentration ([Ca 2+ ] i ) (2 h minimum). However, the cytochrome P450 1A and Ah receptor inhibitor, α-naphtoflavone (a-NF), also inhibited lymphocyte proliferation and did not reverse the effects of 3-MC. Moreover, since a-NF and 3-MC increased [Ca 2+ ] i and inhibited lymphocyte proliferation it was possible that calcium release played a role in 3-MC-inhibited lymphocyte proliferation. The rise in [Ca 2+ ] i induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. Treating cells with 3-MC decreased calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp leucocytes

  4. Comparative studies of mitogen- and antigen-induced lymphocyte proliferation in four captive rhinoceros species.

    Science.gov (United States)

    Vance, Carrie K; Kennedy-Stoskopf, Suzanne; Obringer, Amy R; Roth, Terri L

    2004-12-01

    Cellular immune function in four rhinoceros species was evaluated by way of in vitro lymphocyte proliferation responses to mitogenic and antigenic stimuli to establish normative data on white blood cell activity for each species and to identify species-specific differences that might help explain the predisposition of black rhinoceroses (Diceros bicornis) to disease. A cross section of the U.S. rhinoceros population encompassing all four captive species was sampled, including the Sumatran rhinoceros (Dicerorhinus sumatrensis) (n = 3); Indian rhinoceros (Rhinoceros unicornis) (n = 4); African black rhinoceros (n = 16); and African white rhinoceros (Ceratotherium simum) (n = 10). Of the four species evaluated, African black rhinoceroses exhibited the weakest (P white rhinoceroses, Indian rhinoceroses, and Sumatran rhinoceroses. However, lymphocyte response to bacterial endotoxin lipopolysaccharide was similar (P > 0.05) across species. Antigenic stimulation produced much weaker responses than mitogenic stimulation. No differences (P > 0.05) were observed among rhinoceros species in response to 1 and 10 microg/ml of Leptospira icterohemorrhagiae or Leptospira gryppotyphosa. Lymphocytes from African white rhinoceroses proliferated weakly in the presence of Aspergillus fumigatus filtrate, whereas lymphocytes from the southern black rhinoceros subspecies appeared slightly suppressed in the presence of increasing doses (0.1, 1, and 10 microg/ml) of Aspergillus filtrate. This comparative data set characterizing lymphocyte proliferation in the rhinoceros reveals several differences in immune cell responses among rhinoceros species and provides some evidence that lymphocytes of captive African black rhinoceroses are less vigorous than those of the other rhinoceros species.

  5. SPONTANEOUS IMMUNOGLOBULIN-SYNTHESIZING ACTIVITY OF B LYMPHOCYTES IN INFLAMMATORY RHEUMATIC DISEASES

    Directory of Open Access Journals (Sweden)

    A.T. T. Mamasaidov

    2007-01-01

    Full Text Available Abstract. The aim of present work was to evaluate clinical significance of B-lymphocytes spontaneous antibody-synthesizing activity by B-lymphocytes (LASA in patients with rheumatic inflammatory diseases (RD, i.e., reactive arthritis (ReA, ankylosing spondylitis (AS, rheumatoid arthritis (RA, and systemic lupus erythematosus (SLE. Significantly higher LASA levels were revealed in the patients with ReA, AS, RA, and SLE, as compared with healthy persons and patients with osteoarthrosis. Clinical significance of LASA indexes and their changes may reflect manifestation and degree of immunological activities in ReA, AS, RA, and SLE.

  6. Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

    International Nuclear Information System (INIS)

    Yi, P.I.; Beck, G.; Zucker, S.

    1981-01-01

    Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins [very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)] and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms

  7. Maintenance of CD8+memory T lymphocytes in the spleen but not in the bone marrow is dependent on proliferation.

    Science.gov (United States)

    Siracusa, Francesco; Alp, Özen Sercan; Maschmeyer, Patrick; McGrath, Mairi; Mashreghi, Mir-Farzin; Hojyo, Shintaro; Chang, Hyun-Dong; Tokoyoda, Koji; Radbruch, Andreas

    2017-11-01

    It is current belief that numbers of CD8 + memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here, we compare the proliferation of CD8 + memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and bone marrow (BM). Fifty percent of CD8 + memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8 + memory T lymphocytes are maintained by proliferation. The numbers of CD8 + memory T lymphocytes in the BM, however, were not affected by cyclophosphamide. This stability was independent of circulating CD8 + memory T cells, blocked by FTY720, showing that BM is a privileged site for the maintenance of memory T lymphocytes, as resident cells, resting in terms of proliferation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.

  8. Extremely low frequency pulsed electromagnetic fields increase cell proliferation in lymphocytes from young and aged subjects

    Energy Technology Data Exchange (ETDEWEB)

    Cossarizza, A.; Monti, D.; Bersani, F.; Cantini, M.; Cadossi, R.; Sacchi, A.; Franceschi, C.

    1989-04-28

    The effect of the in vitro exposure to extremely low frequency pulsed electromagnetic fields (PEMFs) on the proliferation of human lymphocytes from 24 young and 24 old subjects was studied. The exposure to PEMFs during a 3-days culture period or during the first 24 hours was able to increase phytohaemagglutinin-induced lymphocyte proliferation in both groups. Such effect was greater in lymphocytes from old people which showed a markedly reduced proliferative capability and, after PEMF exposure, reached values of /sup 3/H-TdR incorporation similar to those of young subjects. The relevance of these data for the understanding and the reversibility of the proliferative defects in cells from aged subjects and for the assessment of risk related to the environmental exposure to PEMFs has to be considered.

  9. Extremely low frequency pulsed electromagnetic fields increase cell proliferation in lymphocytes from young and aged subjects

    International Nuclear Information System (INIS)

    Cossarizza, A.; Monti, D.; Bersani, F.; Cantini, M.; Cadossi, R.; Sacchi, A.; Franceschi, C.

    1989-01-01

    The effect of the in vitro exposure to extremely low frequency pulsed electromagnetic fields (PEMFs) on the proliferation of human lymphocytes from 24 young and 24 old subjects was studied. The exposure to PEMFs during a 3-days culture period or during the first 24 hours was able to increase phytohaemagglutinin-induced lymphocyte proliferation in both groups. Such effect was greater in lymphocytes from old people which showed a markedly reduced proliferative capability and, after PEMF exposure, reached values of 3 H-TdR incorporation similar to those of young subjects. The relevance of these data for the understanding and the reversibility of the proliferative defects in cells from aged subjects and for the assessment of risk related to the environmental exposure to PEMFs has to be considered

  10. Effect of catecholamines and thermal exposure on lymphocyte proliferation, IL-1α & β in buffaloes

    Directory of Open Access Journals (Sweden)

    R.C. Upadhyay

    2010-02-01

    Full Text Available In order to study the effect of catecholamines (epinephrine/norepinephrine and thermal exposure on in vitro buffalo Lymphocyte Proliferation (LP apparently healthy 2- 2 1/2 years old Murrah buffalo heifers maintained as per the standard feeding and management practices were selected from Institute herd. Jugular blood was collected in the forenoon on the day of experiment and processed for Total Leucocyte Count (TLC and Differential Leucocyte Count (DLC. Lymphocyte proliferation assays were performed using whole blood and cells were incubated with epinephrine and norepinephrine (1, 1.5,2 ng/ml at 37oC with 5% CO2. Cells were counted after 72 hrs of incubation and Lymphocyte Proliferation Index (LPI was calculated. Thermal stress effect on the cultures was observed after exposure at 45oC for 4 hr after 72hrs of incubation. The cells were separated from media and media was used for analysis of IL-1α & 1β by ELISA kit. Lymphocyte proliferation Index decreased in responses to Epinephrine and Norepinephrine (P<0.01. Concentration of epinephrine and norepinephrine (1, 1.5,2 ng /ml had no distinguishable effect on LPI. IL-1α & IL-1β levels when compared with control in supernatant (exposed to 45°C were low (P<0.01 and P<0.05, respectively. There was a significant positive correlation between LPI and IL-1α (r=0.80; P<0.01 and between LPI and IL-1β (r=0.78; P<0.05. The study indicated that lymphocyte proliferation in vitro and IL-1α & β levels were affected by catecholamines and thermal exposure. Further the levels of catecholamines had significant (P<0.01 negative effect on LPI indicating that catecholamines levels modulate immunity through IL-1α and IL-1β in buffaloes.

  11. Endothelial cells promote the proliferation of lymphocytes partly through the Wnt pathway via LEF-1

    International Nuclear Information System (INIS)

    Wang, Shu-Hong; Nan, Ke-Jun; Wang, Yao-Chun

    2009-01-01

    The function of T cells and B cells is to recognize specific 'non-self' antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. Endothelial cells (ECs) can trigger the activation of T cells through their class I and class II MHC molecules. In this study, we examined the effect of ECs on the proliferation of lymphocytes. We report that the proliferation of T and B cells can be improved by interaction with ECs. LEF-1 is one of the main molecular mediators in this process, and the inhibition of LEF-1 induces apoptosis. These results suggest that LEF-1 modulates positively the proliferation of lymphocytes induced by their interaction with ECs.

  12. Effects of mercury on the proliferation of human peripheral lymphocytes in vitro

    International Nuclear Information System (INIS)

    Piwecka, K.; Poniedzialek, B.; Rzymski, P.; Karczewski, J.; Zurawski, J.; Wiktorowicz, K.

    2011-01-01

    Our project aimed to investigate the effects of mercury on the proliferation of human peripheral lymphocytes in vitro. The lymphocytes were isolated from the blood collected from healthy donors at Regionalne Centrum Krwiodawstwa i Krwiolecznictwa in Poznan, Poland. For the purpose of cell culture, the lymphocyte suspension (25 · 10 4 cells/ml) in Eagle's medium supplemented with 10% fetal calf serum was prepared. Phytohaemagglutinin-L (PHA-L) was used in a concentration of 2.5 mg/ml to stimulate cell proliferation. Mercuric chloride (HgCl 2 ) in four different concentrations (1 μM, 10 μM, 50 μM, 100 μM) and [3H]-thymidine were added after 48 hours of incubation and the cell culture was continued for the next 24 hours. The rate of lymphocyte proliferation was measured by [3H]-thymidine incorporation method with a liquid scintillation counter. Results indicate that higher concentrations of mercury (50 μM, 100 μM) inhibit the [3H]-thymidine incorporation of human peripheral lymphocytes in vitro. The incorporation was lower than the control sample by 65% at a concentration of 50 μM, while at a concentration of 100 μM it fell to virtually zero. Moreover, the phase of lymphocyte proliferation cycle affected by mercuric chloride was also investigated. For this purpose HgCl 2 in 2 concentrations (10 μM, 50 μM) was added to the cell culture in 4 different time points: at the start of the cell culture and after 4, 24, and 48 hours of incubation. After 48 hours, [3H]-thymidine was added and the cell culture was continued for an additional 24 hours. The rate of cell proliferation was estimated by [3H]-thymidine incorporation using a liquid scintillation counter. The inhibition effect was observed in samples with metal added at the start of the cell culture and after 4 h of incubation, i.e. at the initial phase of the lymphocyte proliferation cycle. (authors)

  13. The role of glutathione in lymphocyte activation and proliferation

    International Nuclear Information System (INIS)

    Messina, J.P.

    1990-01-01

    The object of this work was to establish the requirement for GSH and cystine during the activation and proliferation of human peripheral blood mononuclear cells (PBMC). In the author's initial experiments the intracellular GSH content of PBMC was altered by continuous culture or pretreatment with BSO, a specific inhibitor of GSH synthesis. His results demonstrate that, continuous culture of mitogen stimulated PBMC in the presence of BSO inhibited entry into S-phase of the cell cycle and produced a simultaneous decrease in intracellular GSH. The influence of BSO on early activation events were determined by BSO pretreatment. Extensive depletion (>90%) of the intracellular GSH level prior to mitogenic stimulation did not impair the ability of these cells to produce IL-2 and express IL-2R, indicating that GSH may not be involved in the generation and response to early activation signals. Furthermore, the removal of BSO from these cultures rapidly reversed its inhibitory effects on DNA and GSH synthesis. Cystine transport activities and metabolism by PBMC were characterized in order to examine its contributions to intracellular GSH and early activation proteins. In spite of the ability of cystine to sustain the proliferative response of PBMC, differences in the kinetics of cystine and cysteine uptake indicated that separate transport systems may be operational. Treatment with 2ME enhanced cystine uptake, but lowered the proliferative responses of these cells. Metabolic studies with [ 35 S] cystine demonstrated that mitogen stimulation of PBMC enhance cystine uptake

  14. Spontaneous Retroperitoneal Hemorrhage in a Patient with Prolymphocytic Transformation of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Gwynivere A. Davies

    2013-01-01

    Full Text Available Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and a white blood cell count of 500 000 with prolymphocytes on peripheral blood examination. Chlorambucil and dexamethasone were initiated. He developed progressive anemia during his admission with no clear cause on initial CT examination. Bilateral hip pain began several days later and he was unfortunately diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This condition is rare and generally occurs in those receiving therapeutic anticoagulation or dialysis, with known bleeding disorders or vascular malformation, none of which were present in our patient. Pathology revealed marked leukemoid engorgement of the vessels of many organs with prolymphocytes. We discuss the potential etiologies and relationships between these critical diagnoses.

  15. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

    Energy Technology Data Exchange (ETDEWEB)

    Klein, T.; Pross, S.; Newton, C.; Friedman, H.

    1986-03-05

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by /sup 3/H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects.

  16. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

    International Nuclear Information System (INIS)

    Klein, T.; Pross, S.; Newton, C.; Friedman, H.

    1986-01-01

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by 3 H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects

  17. Flavonol robinobiosides and rutinosides from Alternanthera brasiliana (Amaranthaceae and their effects on lymphocyte proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Brochado Claudia de O.

    2003-01-01

    Full Text Available The extract of the medicinal species Alternanthera brasiliana Kuntze afforded six di- and triglycosyl kaempferol and quercetin derivatives. Their structures were elucidated based on the ¹H- and 13C-NMR data and are reported here for the first time in this genus. Kaempferol 3-O-robinobioside and kaempferol 3-O-rutinoside significantly inhibited the human lymphocyte proliferation in vitro.

  18. Flavonol robinobiosides and rutinosides from Alternanthera brasiliana (Amaranthaceae) and their effects on lymphocyte proliferation in vitro

    OpenAIRE

    Brochado,Claudia de O.; Almeida,Ana P. de; Barreto,Beatriz P.; Costa,Leandro P.; Ribeiro,Luciene S.; Pereira,Rachel L. da C.; Koatz,Vera L. Gonçalves; Costa,Sonia S.

    2003-01-01

    The extract of the medicinal species Alternanthera brasiliana Kuntze afforded six di- and triglycosyl kaempferol and quercetin derivatives. Their structures were elucidated based on the ¹H- and 13C-NMR data and are reported here for the first time in this genus. Kaempferol 3-O-robinobioside and kaempferol 3-O-rutinoside significantly inhibited the human lymphocyte proliferation in vitro. O extrato da espécie medicinal Alternanthera brasiliana Kuntze forneceu seis derivados di- e triglicosi...

  19. The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results

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    L. Migliore

    2011-09-01

    Full Text Available Objective: aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc or diffuse (dSSc Systemic Slerosis, using the micronucleus (MN assay. Methods: we evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. Results: compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8±4.5 vs. 27.8±13.7, p<0.001. No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1±17.0 and 19.8±2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9±15.0, as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7±8.2. Conclusions: our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies.

  20. Flow Cytometric Analysis of Leishmania Reactive CD4+/CD8+ Lymphocyte Proliferation in Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    H Keshavarz

    2008-12-01

    Full Text Available Background: Determination of the division history of T cells in vitro is helpful in the study of effector mechanisms against infections. Technique described here uses the intracellular fluorescent label carboxyfluorescein diacetate succinimidyl ester (CFSE to monitor the proliferation. Methods: In a cross sectional study, blood samples were collected from 7 volunteers with history of cutaneous leishmania­sis (CL and one healthy control from endemic areas in Isfahan province who referred to the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL, then CD4+/CD8+ lymphocytes and CD14+ monocytes were isolated from peri­pheral blood mononuclear cells (PBMC using mAbs and magnetic nanoparticles. CFSE labeled CD4+ or CD8+ lympho­cytes cultured with autologous monocytes in the presence of PHA, SLA, live Leishmania major or as control with­out sti­mulation. Cells were harvested after 7 days and were analyzed using flow cytometry. Results: Five consecutive divisions were monitored separately. Stimulation of CD4+ or CD8+ lymphocytes from CL sub­jects with SLA showed a significant difference in proliferation comparing with unstimulated cells (P< 0.05. The signifi­cant difference in the percentages of CD4+ cells stimulated with SLA was revealed at different divisions for each subject. In CD8+ lymphocyte, significant stronger stimulation of SLA was evident later in the proliferation process. The mean number of divisions in both CD4+/CD8+ lymphocytes stimulated with SLA was significantly greater than when stimulated with live L. major (P=0.007 / P=0.012, respectively Conclusion: The percentage of divided cells might be calculated separately in each division. The cells remained active following CFSE staining and there is possibility of functional analysis simultaneously.

  1. Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages.

    Science.gov (United States)

    Routray, Indusmita; Ali, Shakir

    2016-01-01

    Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.

  2. Boron Affects Immune Function Through Modulation of Splenic T Lymphocyte Subsets, Cytokine Secretion, and Lymphocyte Proliferation and Apoptosis in Rats.

    Science.gov (United States)

    Jin, Erhui; Li, Shenghe; Ren, Man; Hu, Qianqian; Gu, Youfang; Li, Kui

    2017-08-01

    This study demonstrated the mechanisms of boron effects in a rat model and provided a scientific basis for the rational of boron use. These findings were achieved by investigating the effects of boron (10, 20, 40, 80, 160, 320, and 640 mg/L in drinking water or 1.5, 3, 6, 12, 24, 48, and 96 mg/kg BW) on rat serum immunoglobulins (IgGs), splenic cytokines, lymphocyte subsets, as well as on lymphocyte proliferation and apoptosis. Addition of 20 (3) and 40 (6) mg/L (mg/kg BW) of boron to drinking water significantly increased rat serum IgG concentrations, splenic IFN-γ and IL-4 expression as well as the number of splenic CD3 + , CD4 + and proliferating cell nuclear antigen (PCNA) + cells. Supplementation of drinking water with 40 mg/L (6 mg/kg BW) boron also markedly increased splenic IL-2 expression and the CD4 + /CD8 + cell ratio and reduced splenic CD8 + cell number. Supplementation with 80 mg/L (12 mg/kg BW) boron significantly increased CD3 + and PCNA + cell numbers (P boron markedly reduced the serum IgG concentrations; splenic IL-2 and IL-10 expression; the number of CD3 + , CD4 + and PCNA + cells; and increased the number of splenic CD8 + and caspase-3 + cells and promoted caspase-3 expression in CD3 + cells. In conclusion, these findings suggest that the supplementation of rat drinking water with 20(3) and 40(6) mg/L (mg/kg BW) boron can markedly enhance humoral and cellular immune functions, while boron concentrations above 320 mg/L (48 mg/kg BW) can have an inhibitory effect or even toxicity on immune functions. These results exhibit a U-shaped response characteristic of low and high doses of boron supplementation on immune function and imply that proper boron supplementation in food for humans and animals could be used as an immunity regulator.

  3. Spontaneous Apoptosis, Oxidative Status and Immunophenotype Markers in Blood Lymphocytes of AIDS Patients

    Directory of Open Access Journals (Sweden)

    Gabriele A. Losa

    2000-01-01

    Full Text Available Peripheral blood mononuclear cells (PBMC from 251 HIV‐positive drug abusers of known clinical stage and from 40 healthy donors were tested for conventional immunologic markers (CD3, CD4, CD8, CD19, CD14, CD16/CD56, CD45 and HLA‐DR. Additional cell parameters and the occurrence of spontaneous apoptosis (programmed cell death were investigated on freshly isolated PBMC by flow cytometric measurement of either annexin‐V bound to plasma membrane phosphatidylserine or propidium iodide uptake. The activity of γ‐glutamyltransferase (γ‐GT, an ectoenzyme contributing to the synthesis of the intracellular antioxidant glutathione (GSH and involved in early apoptosis, was also determined in these cells. Immunocompetent T‐cell counts were lower in HIV+ patients, with the exception of CD8+ and HLA‐DR+ lymphocytes. The external binding of annexin‐V was significantly higher in HIV+ PBMC and occurred in both CD8+ and CD4+ T‐lymphocyte subsets. The activity of γ‐GT, was significantly lower in the PBMC from HIV+ patients, indicating that the redox status of PBMC may be affected in HIV+ individuals. Finally, the most dominant features characterising patients receiving antiretroviral therapy were greater long‐term stability in the distribution of various cell parameters excepted the level of apoptosis.

  4. Chromosome dosimetry: the influence of culture media on the proliferation of irradiated and unirradiated human lymphocytes

    International Nuclear Information System (INIS)

    Purrott, R.J.; Lloyd, D.C.; Vulpis, N.

    1981-01-01

    The proliferation of phytohaemagglutinin stimulated human lymphocytes in four types of synthetic culture medium has been studied using the fluorescence plus Giemsa staining technique to determine cell cycle status. 48 hour cultures of unirradiated cells containing Ham's F10 or RPMI 1640 media yielded significant numbers of second cycle metaphases. Cultures containing Eagle's MEM or TC 199 media, however, required longer incubation times to produce appreciable numbers of second division cells. Intrinsic differences between donors in the rate of proliferation had little effect on the relative ranking of the media. Radiation induced mitotic delay of about 1 hour per Gray was observed for each medium. The relevance of these results to the accuracy of radiation dose estimation by chromosome aberration analysis is discussed. (author)

  5. Evaluation of Maternal Serum 25-Hydroxyvitamin D, Paraoxonase 1 Levels, and Neutrophil-to-Lymphocyte Ratio in Spontaneous Preterm Birth.

    Science.gov (United States)

    Bozoklu Akkar, Ozlem; Sancakdar, Enver; Karakus, Savas; Yildiz, Caglar; Akkar, Ismail; Arslan, Murat; Sahin, Irfan Oguz; Imir Yenicesu, Ayse Gonca; Cetin, Ali

    2016-04-13

    BACKGROUND The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. MATERIAL AND METHODS This study was prospectively administered in women referred to our obstetrics service with preterm labor that resulted in preterm birth (n=35) and term labor that ended in term birth (n=44). The maternal serum levels of 25-hydroxyvitamin D and paraoxonase 1 were measured and neutrophil-to-lymphocyte ratio was calculated. RESULTS The 25-hydroxyvitamin D and paraoxonase 1 levels of the preterm group were significantly lower than those of the term group (pparaoxonase 1 in the preterm group (r=0.35; p=0.021). CONCLUSIONS Decreased maternal serum 25-hydroxyvitamin D and paraoxonase 1 levels and increased neutrophil-to-lymphocyte ratio may have a role in the etiology of spontaneous preterm birth.

  6. Effect of propolis on mitotic and cellular proliferation indices in human blood lymphocytes

    International Nuclear Information System (INIS)

    Montoro, A.; Almonacid, M.; Villaescusa, J.; Barquinero, J.; Barrios, L.; Verdu, G.; Perez, J.

    2006-01-01

    The study of the frequency of chromosomal aberrations per cell is the tool used in Biological dosimetry studies. Using dose-effect calibration curve obtained in our laboratory, we can evaluate the radioprotector effect of the EEP (ethanolic extract of propolis) in cultures in vitro. Propolis is the generic name for resinous substance collected by honeybees. The results showed a reduction in chromosomal aberrations's frequency of up to 50 %. The following study consisted of analyzing human peripheral blood lymphocytes exposed to 2 Gy γ rays, in presence and absence of EEP, the change in the frequency of chromosome aberrations was analysed with biological dosimetry. The protection against the formation of dicentric and ring was dose-dependent, but there seemed to be a maximum protection, i.e. a further increase in the concentration of EEP does not show additional protection. This work studies the effect of the EEP of the cellular cycle using the mitotic and cellular proliferation index, as an alternative for the screening cytostatic activity. The results indicate that the lymphocytes which were cultures in presence of EEP exhibited a significant and dependent-concentration decrease in mitotic index and proliferation kinetics. The possible mechanisms involved in the radioprotective influence of EEP are discussed. (authors)

  7. Corticosteroid-induced suppression of in vitro lymphocyte proliferation in four captive rhinoceros species.

    Science.gov (United States)

    Roth, Terri L; Vance, Carrie K

    2007-12-01

    Captive African black rhinoceroses (Diceros bicornis) are unusually susceptible to several diseases not commonly observed in any of the other three rhinoceros species maintained in captivity. The potential role of corticosteroids (either endogenously produced or exogenously administered) in the development of these sometimes fatal diseases has been questioned. In this study, the suppressive effects of two therapeutic corticosteroids (dexamethasone and hydrocortisone) on in vitro lymphocyte proliferation was examined in four rhinoceros species, including the Sumatran rhinoceros (Dicerorhinus sumatrensis, n = 3), Indian rhinoceros (Rhinoceros unicornis, n = 4), African black rhinoceros (n = 10), and African white rhinoceros (Ceratotherium simum, n = 5). Three blood samples collected from each rhinoceros 1 mo to 1 yr apart provided replicates for the study. Both dexamethasone and hydrocortisone suppressed (P rhinoceros cell proliferation in response to any of the four mitogens was never completely suppressed, even in cultures containing the highest steroid concentration tested (10(-3) M). The effect of the two corticosteroids differed slightly among the rhinoceros species and subspecies tested, but there was no evidence that eastern or southern black rhinoceros lymphocytes were more sensitive to the suppressive effects of corticosteroids than the other rhinoceros species.

  8. Effect of propolis on mitotic and cellular proliferation indices in human blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Montoro, A.; Almonacid, M.; Villaescusa, J. [Valencia Hospital Univ. la Fe, Servicio de Proteccion Radiologica (Spain); Barquinero, J. [Barcelona Univ. Autonom, Servicio de Dosimetria Biologica, Unidad de Antropologia, Dept. de Biologia Animal, Vegetal y Ecologia, barcelona (Spain); Barrios, L. [Barcelona Univ. Autonoma, Dept. de Biologia Celular y Fisiologia. Unidad de Biologia Celular (Spain); Verdu, G. [Valencia Univ. Politecnica, Dept. de Ingenieria Quimica y Nuclear (Spain); Perez, J. [Hospital la Fe, Seccion de Radiofisica, Servicio de Radioterapia, valencia (Spain)

    2006-07-01

    The study of the frequency of chromosomal aberrations per cell is the tool used in Biological dosimetry studies. Using dose-effect calibration curve obtained in our laboratory, we can evaluate the radioprotector effect of the EEP (ethanolic extract of propolis) in cultures in vitro. Propolis is the generic name for resinous substance collected by honeybees. The results showed a reduction in chromosomal aberrations's frequency of up to 50 %. The following study consisted of analyzing human peripheral blood lymphocytes exposed to 2 Gy {gamma} rays, in presence and absence of EEP, the change in the frequency of chromosome aberrations was analysed with biological dosimetry. The protection against the formation of dicentric and ring was dose-dependent, but there seemed to be a maximum protection, i.e. a further increase in the concentration of EEP does not show additional protection. This work studies the effect of the EEP of the cellular cycle using the mitotic and cellular proliferation index, as an alternative for the screening cytostatic activity. The results indicate that the lymphocytes which were cultures in presence of EEP exhibited a significant and dependent-concentration decrease in mitotic index and proliferation kinetics. The possible mechanisms involved in the radioprotective influence of EEP are discussed. (authors)

  9. Identification of Staphylococcal Enterotoxin B Sequences Important for Induction of Lymphocyte Proliferation by Using Synthetic Peptide Fragments of the Toxin

    Science.gov (United States)

    1994-08-01

    Staphylococcal Enterotoxin B Sequences STO=T Important for induction of lymphocyte proliferatio WPP8, WPPM,by using synthetic peptide fragments of the...Lymphocyte Proliferation by Using Synthetic Peptide Fragments of the Toxin MARTI JETT.I* ROGER NEILL,’ CHRISTOPHER WELCH,’ THOMAS BOYLE,’ EDWARD BERNTON...fragment of SEC (41) and for an amino- ment of endotoxic shock (42), induction of immunosuppres- terminal synthetic peptide of SEA (36). Another study

  10. Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Mohammad Hojjat-Farsangi

    Full Text Available ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients.Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9 and healthy donors (n = 6. IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay.The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05.ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.

  11. TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Hong, Ming; Xia, Yi; Zhu, Yu; Zhao, Hui-Hui; Zhu, Han; Xie, Yue; Fan, Lei; Wang, Li; Miao, Kou-Rong; Yu, Hui; Miao, Yu-Qing; Wu, Wei; Zhu, Hua-Yuan; Chen, Yao-Yu; Xu, Wei; Qian, Si-Xuan; Li, Jian-Yong

    2016-11-01

    Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, β2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A study of the effect of salicylic acetic acid on a lymphocyte cell model of cellular activation and proliferation.

    Science.gov (United States)

    Aguilar, Enrique Aranda; de la Haba-Rodríguez, Juan; Macho, Antonio; Lucena, Concha; Gómez, Auxiliadora; Calzado, Marco; Muñoz, Eduardo

    2006-01-18

    Salicylic acetic acid (SAA) is a drug that has formed part of the treatment of many diseases for many years. Its anti-inflammatory activity is well known, but recently its possible role in the interference in the oncogenesis mechanisms has become apparent. With the aim of supporting these yet preliminary observations, we studied the effect of salicylic acetic acid on a cellular activation and proliferation model. We used lymphocytes obtained from peripheral blood, which were later exposed to cellular activation and proliferation stimulus by the SEB antigen. Lymphocyte activation was determined by direct immunoflourescence through expression of the receptor IL-2 (CD25) alpha chain and proliferation through the incorporation of tritiated thymidine to the DNA in synthesis together with the determination of the cellular cycle by flow cytometry. We found that both processes, activation and proliferation, are inhibited by increasing doses of SAA.

  13. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    International Nuclear Information System (INIS)

    Bolzan, Alejandro D.; Bianchi, Martha S.; Gimenez, Esteban M.; Flaque, Maria C. Diaz; Ciancio, Vicente R.

    2008-01-01

    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals

  14. Comparative Analysis of Spontaneous and Stimulus-Evoked Calcium Transients in Proliferating and Fifferentiating Human Midbrain-Derived Stem Cells

    DEFF Research Database (Denmark)

    Johansen, Torben; Krabbe, Christina; Schmidt, Sissel Ida

    2017-01-01

    Spontaneous cytosolic calcium transients and oscillations have been reported in various tissues of nonhuman and human origin but not in human midbrain-derived stem cells. Using confocal microfluorimetry, we studied spontaneous calcium transients and calcium-regulating mechanisms in a human ventra...... cells that provides evidence for the mechanisms that are likely to be involved. We propose that the observed spontaneous calcium transients may contribute to mechanisms involved in cell proliferation, phenotypic differentiation, and general cell maturation....

  15. 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...... in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess......, 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...

  16. p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Armesilla-Diaz, Alejandro, E-mail: aarmesilla@cib.csic.es [Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid (Spain); Elvira, Gema; Silva, Augusto [Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid (Spain)

    2009-12-10

    Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, a shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC.

  17. Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

    Directory of Open Access Journals (Sweden)

    Bakari Muhammad

    2009-02-01

    Full Text Available Abstract Background Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA in HIV-infected subjects with latent or active TB. Methods HIV-infected subjects with bacille Calmette Guérin (BCG scars and CD4 counts ≥ 200 cells/mm3 entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST, LPA and five day assays of interferon gamma (IFN-γ release. Assay antigens were early secreted antigenic target 6 (ESAT-6, antigen 85 (Ag85, and Mycobacterium tuberculosis whole cell lysate (WCL. Subjects were screened for active TB at enrollment by history, exam, sputum smear and culture. We compared antimycobacterial immune responses between subjects with and without latent or active TB at enrollment. Results Among 1885 subjects screened, 635 had latent TB and 13 had active TB. Subjects with latent TB were more likely than subjects without TB to have LPA responses to ESAT-6 (13.2% vs. 5.5%, P Conclusion Lymphoproliferative responses to mycobacteria are detectable during HIV-associated active TB, and are less sensitive but more specific than TST. Trial registration ClinicalTrials.gov Identifier NCT00052195.

  18. Detection of nickel and palladium contact hypersensitivity by a flow cytometric lymphocyte proliferation test.

    Science.gov (United States)

    Spoerri, I; Scherer, K; Michel, S; Link, S; Bircher, A J; Heijnen, I A F M

    2015-03-01

    We established a flow cytometric lymphocyte proliferation test (LPT) for the detection of nickel (Ni) and palladium (Pd) sensitization. Eighty-one consecutive patients with an indication for patch test (PT) were tested by LPT with Ni (NiSO4 ) and Pd (Na2 PdCl4 and PdCl2 ) salts. The imprecision of the LPT was low (coefficient of variation 7.2%). Using PT as a diagnostic reference, the sensitivity and specificity of LPT were 74.4% and 80% for NiSO4 , 74.4% and 78.3% for Na2 PdCl4 , and 57.2% and 85.4% for PdCl2 , respectively. For both Ni and Pd, the likelihood ratio for a positive PT markedly increased with increasing LPT value. With medical history as a reference, the sensitivity and specificity were 40.6% and 82.1% for LPT and 59.4% and 89.7% for PT, respectively. Combination of LPT and PT resulted in a higher specificity of 95%, albeit lower sensitivity of 34.4%. In conclusion, flow cytometric LPT represents a reliable and useful method for the detection of Ni and Pd sensitization. LPT values correlate with PT results and, when used in combination with PT, increase test specificity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Bolzan, Alejandro D. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina)], E-mail: abolzan@imbice.org.ar; Bianchi, Martha S. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina); Gimenez, Esteban M.; Flaque, Maria C. Diaz [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Ciancio, Vicente R. [Universidad Nacional de La Plata, Facultad de Ciencias Medicas, 120 y 60, 1900 La Plata (Argentina)

    2008-03-01

    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p < 0.05). BLM sensitivity test showed that aircrew and controls are equally sensitive to BLM G2 clastogenic effects, since both groups exhibited a similar frequency of chromatid breaks per cell (p > 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals.

  20. [Effect of Heat Shock Protein 90 Inhibitor 17-DMAG on Proliferation and Apoptosis of Acute Lymphocytic Leukemia Cell Line Jurkat].

    Science.gov (United States)

    Ge, Fang-Fang; Guo, Rong; Tian, Wen-Liang; Gao, Feng-Cai; Sun, Ling; Jiang, Zhong-Xing

    2017-08-01

    To explore the effect of heat shock protein 90(HSP90) inhibitor 17-DMAG, an inhibitor specific for heat shock protein 90, on the proliferation and apoptosis of acute lymphocytic leukemia cell lines Jurkat. Jurkat cells were collected, then were treated with 17-DMAG. The expression of HSP90 was examined by semi-quantitative RT-PCR analysis, the effect of 17-DMAG on cell proliferation were detected by using WST, and cell apoptosis were detected by using flow cytometry with Annexin V/PI double stenining. After Jurkat cells were treated with different concentrations of 17-DMAG for 48 hours, the HSP90 mRNA expression decreased significantly in dose dependent manner (r=0.9530, PJurkat cells were treated with 17-DMAG for 48 h; after treating Jurkat cell with 17-DMAG, the cell proliferation was inhibited(r=0.9903, PJurkat cell proliferation and induce the Jurkat cell apoptosis.

  1. Segregation of B lymphocytes into stationary apoptotic and migratory proliferating subpopulations in agglomerate cultures with ileal epithelium.

    Science.gov (United States)

    Alitheen, N; McClure, S; McCullagh, P

    2001-09-01

    The B lymphocyte-epithelial cell interactions that define the microenvironment of the ileal Peyer's patch, the primary B lymphocyte organ of the fetal lamb, have been replicated in tissue culture. Mixed suspensions of ileal epithelial cells, lymphocytes and fibroblasts from fetuses of 63-103 days of gestation organized into macroscopically visible agglomerates within 72 h. These agglomerates contained translucent spherical cavities and were enclosed within a marginal cell layer and surrounded by an expanding corona of emigrating cells. The lining of the cavities and the marginal layer consisted of well-differentiated, polarized columnar ileal epithelial cells. One population of B lymphocytes in the initial mixed suspension differentiated into two discrete populations reproducing the characteristics of intact fetal ileal Peyer's patches. B cells apposed to follicle-associated epithelium (FAE) within agglomerates underwent apoptosis. The other population of emigrant B cells proliferated and expressed the BAQ44A differentiation marker. Differentiation of ileal epithelial cells into FAE, typical of Peyer's patches, was markedly accelerated. The mutually inductive influences of intestinal epithelial cells and B lymphocytes in these agglomerates replicate normal mid-gestational fetal development of the mucosal immune system and afford new opportunities for its further investigation.

  2. Effects of orally administered viable Lactobacillus rhamnosus GG and Propionibacterium freudenreichii subsp. shermanii JS on mouse lymphocyte proliferation.

    Science.gov (United States)

    Kirjavainen, P V; ElNezami, H S; Salminen, S J; Ahokas, J T; Wright, P F

    1999-11-01

    Immunomodulation by probiotics is a subject of growing interest, but the knowledge of dose response and time profile relationships is minimal. In this study we examined the effects of Lactobacillus rhamnosus GG (LGG) and Propionibacterium freudenreichii subsp. shermanii JS (PJS) on the proliferative activity of murine lymphocytes ex vivo. Dose dependency was assessed by treating animals perorally with a low or a high dose (i.e., 10(9) or 10(12) viable bacteria/kg of body weight) for 7 days. The lower dose levels of each strain appeared to enhance T-cell proliferation at the optimal concanavalin A (ConA) concentration (by 69 to 84%) and B-cell proliferation at the optimal and supraoptimal concentrations of lipopolysaccharide (by 57 to 82%). B-cell proliferation was also enhanced by the high LGG dose (by 32 to 39%) but was accompanied by a marginal decrease in T-cell proliferation (by 8%) at the optimal ConA concentration. The time profiles of the immune responses were assessed after daily treatment with the higher dose for 3, 7, and 14 days. A significant decrease in basal lymphoproliferation (by 32 to 42%) was observed with PJS treatment after the 3- and 7-day periods; however, this activity returned to control levels after 14 days of treatment, which also resulted in significantly enhanced T-cell proliferation at optimal and supraoptimal ConA concentrations (by 24 to 80%). The 14-day LGG treatment also enhanced the latter activity (by 119%). In conclusion, LGG and PJS have specific dose- and duration-dependent immunomodulatory effects on the proliferative activity of B and T lymphocytes and may also reduce lymphocyte sensitivity to the cytotoxic effects of lectin mitogens.

  3. A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Aysun Adan Gökbulut

    2015-06-01

    Full Text Available INTRODUCTION: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey, on 232B4 chronic lymphocytic leukemia (CLL cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. METHODS: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. RESULTS: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. DISCUSSION AND CONCLUSION: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

  4. Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection.

    Science.gov (United States)

    Kiyici, Murat; Nak, Selim Giray; Budak, Ferah; Gurel, Selim; Oral, Barbaros; Dolar, Enver; Gulten, Macit

    2006-06-01

    Spontaneous ascites infection is a frequently encountered and important complication of decompensated liver cirrhosis. The immune system plays an important role in the development or eradication of this infection. A number of compositional and functional alterations in immune system cells have been demonstrated in cirrhotic patients; however, there is a lack of knowledge about this issue in ascitic infections. The aim of the present study was to evaluate lymphocyte subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in decompensated cirrhotic patients with or without spontaneous ascites infection. The study population consisted of 45 decompensated cirrhotic patients (32 men, 13 women) with different etiologies. Patients with ascitic polymorphonuclear leukocyte count > or =250/mm(3) and/or positive ascitic bacterial cultures were classified as the "infected group". Comparison was made between the infected and non-infected group for the following parameters: ascites leukocyte counts and differentiations; ascitic fluid protein; albumin levels and serum-ascites albumin gradients; flow cytometric detection of cell surface markers for ascitic T, B and natural killer lymphocytes; intracytoplasmic interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma; levels of ascitic IL-8, IL-10, IL-12 and TNF-alpha; and soluble Fas antigen and soluble Fas ligand. The CD4/CD8 ratio was significantly decreased and expression of T cell receptor-gammadelta was increased in the infected group. Furthermore, ascites TNF-alpha levels were also elevated in this group. Ascitic IL-8, IL-10, IL-12 and TNF-alpha levels were significantly higher in patients with positive ascitic bacterial culture. These results suggest that a cytotoxic, especially Th1, immune response predominates in ascites infections. It also demonstrates that TNF-alpha might be involved in the pathogenesis of ascites infections.

  5. Lymphocyte proliferation in response to Brucella abortus 2308 or RB51 antigens in mice infected with strain 2308, RB51, or 19.

    OpenAIRE

    Stevens, M G; Olsen, S C; Pugh, G W

    1994-01-01

    Lymphocyte proliferation to 22 protein fractions (106 to 18 kDa) of Brucella abortus 2308 or the lipopolysaccharide O-antigen-deficient mutant of 2308, strain RB51, was measured for 20 weeks after infection of mice with strain 2308, RB51, or 19. Throughout the 20-week study, the 22 protein fractions of 2308 and RB51 induced a similar pattern of proliferation when they were incubated with lymphocytes from the infected mice. In addition, during the 20 weeks, lymphocytes from all groups of infec...

  6. Spontaneously amplified homochiral organic-inorganic nano-helix complexes via self-proliferation

    Science.gov (United States)

    Zhai, Halei; Quan, Yan; Li, Li; Liu, Xiang-Yang; Xu, Xurong; Tang, Ruikang

    2013-03-01

    Most spiral coiled biomaterials in nature, such as gastropod shells, are homochiral, and the favoured chiral feature can be precisely inherited. This inspired us that selected material structures, including chirality, could be specifically replicated into the self-similar populations; however, a physicochemical understanding of the material-based heritage is unknown. We study the homochirality by using calcium phosphate mineralization in the presence of racemic amphiphilic molecules and biological protein. The organic-inorganic hybrid materials with spiral coiling characteristics are produced at the nanoscale. The resulted helixes are chiral with the left- and right-handed characteristics, which are agglomerated hierarchically to from clusters and networks. It is interesting that each cluster or network is homochiral so that the enantiomorphs can be separated readily. Actually, each homochiral architecture is evolved from an original chiral helix, demonstrating the heritage of the matrix chirality during the material proliferation under a racemic condition. By using the Ginzburg-Landaue expression we find that the chiral recognition in the organic-inorganic hybrid formation may be determined by a spontaneous chiral separation and immobilization of asymmetric amphiphilic molecules on the mineral surface, which transferred the structural information from the mother matrix to the descendants by an energetic control. This study shows how biomolecules guide the selective amplification of chiral materials via spontaneous self-replication. Such a strategy can be applied generally in the design and production of artificial materials with self-similar structure characteristics.Most spiral coiled biomaterials in nature, such as gastropod shells, are homochiral, and the favoured chiral feature can be precisely inherited. This inspired us that selected material structures, including chirality, could be specifically replicated into the self-similar populations; however, a

  7. Effects of short-term restraint stress on leukocyte counts, lymphocyte proliferation and lysis of erythrocytes in gilts.

    Science.gov (United States)

    Roozen, A W; Magnusson, U

    1996-10-01

    The effects of short-term restraint stress on leukocyte counts, lymphocyte proliferation and lysis of erythrocytes were studied in six gilts. A catheter was inserted into the jugular vein and two blood samples were collected before the onset of stress. Thereafter a hog snare was applied and blood samples were collected at 0.5, 2, and 3.5 min after the start of snaring. Neither the total WBC number, nor the total number of lymphocytes, or the total number of polymorphonuclear leukocytes changed significantly throughout the study. This was also true for the degree of intravasal lysis of erythrocytes. In whole blood cultures stimulated with pokeweed mitogen, an increase (P immunity but not the leukocyte count nor lysis of erythrocytes in pigs.

  8. Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Mitxelena, Jone; Sánchez-Quiles, Virginia

    2016-01-01

    that are not clearly understood. To study the role of IL-2 in the regulation of nuclear protein function we have performed an unbiased mass spectrometry-based study of the nuclear phosphoproteome of resting and IL-2-treated CD4(+) T lymphocytes. We detected 8521distinct phosphosites including many that are not yet......Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms...... reported in curated phosphorylation databases. Although most phosphorylation sites remained unaffected upon IL-2 treatment, 391 sites corresponding to 288 gene products showed robust IL-2-dependent regulation. Importantly, we show that ATP-citrate lyase (ACLY) is a key phosphoprotein effector of IL-2...

  9. Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes.

    Science.gov (United States)

    de Abreu Costa, Lucas; Henrique Fernandes Ottoni, Marcelo; Dos Santos, Michaelle Geralda; Meireles, Agnes Batista; Gomes de Almeida, Valéria; de Fátima Pereira, Wagner; Alves de Avelar-Freitas, Bethânia; Eustáquio Alvim Brito-Melo, Gustavo

    2017-11-10

    Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4⁺ (CD4⁺) T lymphocytes and CD8⁺ T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.

  10. Dimethyl Sulfoxide (DMSO Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes

    Directory of Open Access Journals (Sweden)

    Lucas de Abreu Costa

    2017-11-01

    Full Text Available Dimethylsulfoxide (DMSO is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC. However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4+ (CD4+ T lymphocytes and CD8+ T lymphocytes interferon-γ (IFN-γ, tumor necrosis factor-α (TNF-α and interleukin-2 (IL-2 producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.

  11. A microculture system for the measurement of antigen-induced murine lymphocyte proliferation: advantages of 5% horse serum and 5 X 10(-5) M mercaptoethanol.

    Science.gov (United States)

    Brummer, E; Vris, T W; Lawrence, H S

    1977-01-01

    Short term microculture systems which measure murine lymphocyte proliferative responses to mitogens are well established. We demonstrate here that these microculture methods are not suitable for antigen-induced responses because of the high levels of murine lymphocyte proliferation in control cultures associated with the use of fetal calf serum or human serum. We also show that this problem can be eliminated with the use of a combination of 5% horse serum and 5 X 10(-5) M mercaptoethanol. We describe an antigen-induced murine lymphocyte proliferation microculture system in which good stimulation indices are achieved and the lymphocyte proliferation in control cultures remain at a low level throughout the 7 day culture period.

  12. Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens.

    Science.gov (United States)

    Guo, Qingyun; Wang, Zixu; Dong, Yulan; Cao, Jing; Chen, Yaoxing

    2017-09-01

    Previous study has demonstrated that melatonin plays a critical role in monochromatic-light-induced lymphocyte proliferation in response to T cell mitogen concanavalin A (ConA). However, its intracellular mechanism is still unclear. In this study, we investigate the intracellular signal pathways of melatonin receptor-mediated T-lymphocyte proliferation in the spleens of chicks exposed to different light wavelengths. Results showed that green light enhanced T-lymphocyte proliferation by 2.46-6.83% and increased splenic mRNA and protein expressions of melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) by 16.05-40.43% compared with the white, red and blue light groups. However, pinealectomy resulted in a decrease in T-lymphocyte proliferation and melatonin receptor expression with no statistically significant differences between the different light groups. In vitro experiments showed that the Mel1b selective antagonist 4P-PDOT, the Mel1c selective antagonist prazosin and the mitogen-activated protein kinase kinase-1 (MEK-1) inhibitor PD98059 suppressed both melatonin-induced lymphocyte proliferation in response to ConA and melatonin- and ConA-stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) activity but that the Mel1a/Mel1b non-selective antagonist luzindole did not. In addition, pretreatment with forskolin (FSK, the adenylyl cyclase activator), H89 (the PKA inhibitor), U73122 (the PLC inhibitor) or Go6983 (the broad spectrum PKC inhibitor) markedly attenuated melatonin- and ConA-stimulated T-lymphocyte proliferation and ERK1/2 activity. These results demonstrate that melatonin mediates green-light-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors by triggering crosstalk between the cAMP/PKA and PLC/PKC signal pathways followed by ERK1/2 activation.

  13. Age and smoking habit influence on the spontaneous and radiation induced frequencies of the micronucleus in human lymphocytes

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Nasazzi, N.; Heredia, M.L.

    1996-01-01

    Several endpoints have been used for monitoring human population that have been exposed at work or in the environment to genotoxic agents, particularly to ionizing radiation. The cytokinesis-block micronucleus (MN) assay in peripheral lymphocytes is a reliable method for evaluating radiation induced chromosomal damage (DNA breaks and mitotic spindle disturbances) and thus, a suitable dosimeter for estimating in vivo whole body exposures. A research to determine the influence of age, sex and life style factors (smoking habits) on the MN spontaneous and radiation induced frequencies was carried out in order to define the use of this assay in Biological Dosimetry. The estimation of MN frequencies was analyzed in lymphocytes cultures from 50 health donors aged between 4 and 60 years. Based on the smoking habits, they were divided into 2 groups. A fraction of the sample was irradiated in vitro with γ-rays in the range of 0.35 Gy to 4 Gy. A statistically significant influence on the spontaneous MN frequency was observed (R 2 = 0.59) when the variables age and smoking habit were analyzed, and a statistically significant influence on the radiation induced MN frequency was also obtained (R 2 = 0.86) when dose, age and smoking habit were studied. Sex did not influence significantly MN variability, but there was a greater dispersion in the results obtained from female donors, when compared to males, possibly due to the loss of X chromosomes. The comparison of the data from smoking donors to the data from non smoking donors supports the convenience of taking into account the smoking habit for estimating in vivo whole body exposure to γ-rays for doses below 2 Gy. (authors). 8 refs., 3 figs., 2 tabs

  14. Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes.

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    Linxi Qian

    Full Text Available Alkylglycerols (AKGs are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg. Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL transcription of IgG (γ1 mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1/GATA-3 (Th2 flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2. It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1 and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10 were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.

  15. New Alkaloids from Green Vegetable Soybeans and Their Inhibitory Activities on the Proliferation of Concanavalin A-Activated Lymphocytes.

    Science.gov (United States)

    Wang, Taoyun; Zhao, Jianping; Li, Xiaoran; Xu, Qiongming; Liu, Yanli; Khan, Ikhlas A; Yang, Shilin

    2016-03-02

    A comprehensive phytochemical study of the chemical constituents of green vegetable soybeans resulted in the isolation of two new alkaloids, soyalkaloid A, 1, and isoginsenine, 2, together with four known ones, ginsenine, 3, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, 4, (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, 5, and indole-3-carboxylic acid, 6. The structures of compounds 1-6 were elucidated on the basis of spectroscopic and chemical analyses. All of the alkaloids were isolated from soybeans for the first time, and compound 1 was a new indole-type alkaloid with a novel carbocyclic skeleton. Their inhibitory activities on the proliferation of concanalin A-activated lymphocytes were assessed by CCK8 assay.

  16. Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation.

    Science.gov (United States)

    Gouveia de Andrade, Ana Valéria; Bertolino, Giuliana; Riewaldt, Julia; Bieback, Karen; Karbanová, Jana; Odendahl, Marcus; Bornhäuser, Martin; Schmitz, Marc; Corbeil, Denis; Tonn, Torsten

    2015-06-01

    Recently, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been suggested as an alternative to MSCs for the treatment of various inflammatory disorders. However, while a first case report observed beneficial therapeutic effects of repeated MSC-EV infusions in a patient with therapy-refractory graft-versus-host disease, in vitro findings revealed that MSC-EVs were significantly less immunosuppressive than their parental cells. In this study, we compared the immunosuppressive potency of MSCs derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs), with their secreted EVs in a standardized lymphocyte proliferation assay (LPA). Both BM-MSCs and AT-MSCs exhibited a remarkable inhibition of lymphocyte proliferation (LP) (88.1%±1.5% and 75.5%±1.5%, respectively), while isolated EVs derived from them failed to suppress LP at dose levels up to 100 μg/mL. Thus, our data further substantiate previous reports suggesting that cell-cell contact plays an important role on the immunosuppressive potential mediated by MSCs. Hence, MSC-EVs are still a matter of debate and might not be a reasonable substitute for MSCs with regard to the immunosuppressive function. Collectively, these contrasting findings may also reflect the importance of relevant translational aspects when designing new studies. Standardization of MSC culture conditions before EV collection as well as isolation and characterization methods with regard to EV purity are urged. Moreover, before clinical use, dose-finding studies evaluating MSC-EV preparations in suitable preclinical models are warranted.

  17. CD8+ T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever

    Science.gov (United States)

    de Matos, Andréia Manso; Carvalho, Karina Inacio; Rosa, Daniela Santoro; Villas-Boas, Lucy Santos; da Silva, Wanessa Cardoso; Rodrigues, Célia Luiza de Lima; Oliveira, Olímpia Massae Nakasone Peel Furtado; Levi, José Eduardo; Araújo, Evaldo Stanislau Affonso; Pannuti, Claudio Sergio; Luna, Expedito José Albuquerque; Kallas, Esper George

    2015-01-01

    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population. PMID:25675375

  18. CD8+ T lymphocyte expansion, proliferation and activation in dengue fever.

    Directory of Open Access Journals (Sweden)

    Andréia Manso de Matos

    2015-02-01

    Full Text Available Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.

  19. Effects of tartrazine on proliferation and genetic damage in human lymphocytes.

    Science.gov (United States)

    Atlı Şekeroğlu, Zülal; Güneş, Büşra; Kontaş Yedier, Seval; Şekeroğlu, Vedat; Aydın, Birsen

    2017-06-01

    The color additive, tartrazine (TRZ), is widely used in food products, drugs and cosmetics. Genotoxicity of TRZ and its metabolites has not been investigated in detail in the presence and absence of a metabolic activator (S9 mix) in human. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of TRZ and its metabolites on cultured human lymphocytes by using chromosome aberration (CA) and micronucleus (MN) tests. Cultures were treated with 625, 1250 and 2500 μg/ml of TRZ in the presence and absence of S9 mix. TRZ showed cytotoxic activity at the highest concentration due to significant decrease in mitotic index (MI) in the absence of S9 mix when compared with solvent control. TRZ and metabolites significantly increased the CAs and aberrant cells in the presence and absence of S9 mix at the higher concentrations. Increased MN values in cultures with and without S9 mix were found to significantly at the highest concentration when tested. Our results indicated that while both TRZ and its metabolites have genotoxic potential on human lymphocyte cultures with and without S9 mix, TRZ can induce cytotoxicity at the highest concentration in culture without S9 mix under the experimental conditions.

  20. Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

    International Nuclear Information System (INIS)

    Ochoa-Hernández, Alejandra B; Bravo-Cuellar, Alejandro; Jave-Suarez, Luis F; Barros-Núñez, Patricio; Aguilar-Lemarroy, Adriana; Ramos-Solano, Moisés; Meza-Canales, Ivan D; García-Castro, Beatriz; Rosales-Reynoso, Mónica A; Rosales-Aviña, Judith A; Barrera-Chairez, Esperanza; Ortíz-Lazareno, Pablo C; Hernández-Flores, Georgina

    2012-01-01

    WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the WNT7A gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation. We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative WNT7A expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures. WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p ≤0.001). By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway. To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic

  1. Cytokine production and lymphocyte proliferation in patients with Nocardia brasiliensis actinomycetoma.

    Science.gov (United States)

    Méndez-Tovar, Luis J; Mondragón-González, Rafael; Vega-López, Francisco; Dockrell, Hazel M; Hay, Roderick; López-Martínez, Rubén; Manzano-Gayosso, Patricia; Hernández-Hernández, Francisca; Padilla-Desgarennes, Carmen; Bonifaz, Alexandro

    2004-11-01

    IFN-gamma, TNF-alpha, IL-4, IL-10 and IL-12 concentrations in the supernatant of peripheral blood mononuclear cell (PBMC) cultures and the in vitro proliferation of PBMC were studied in 25 patients with actinomycetoma caused by Nocardia brasiliensis and in 10 healthy controls from endemic zones. Cell cultures were stimulated by a N. brasiliensis crude cytoplasmic antigen (NB) and five semi-purified protein fractions (NB2, NB4, NB6, NB8, and NB10) separated by isoelectric. Phytohemagglutinin (PHA) and purified protein derivative (PPD) of Mycobacterium tuberculosis were used as control antigens. Skin tests were performed by injecting 0.1 ml of candidin and PPD intradermally (ID). Patients showed a poor response to tuberculin, while their response to candidin was more than two fold greater than that observed in the controls. Cell proliferation showed no statistically significant differences in either group. IFN-gamma production was higher in the healthy controls than in the patients, whereas TNF-alpha secretion was slightly higher in the patients' cultures. IL-4 was detected in the patients' cultures but not in the controls. IL-10 and IL-12 were present at low concentrations in both groups. These results suggest that patients with actinomycetoma show normal antigen recognition, but with low IFN-gamma production, and higher concentrations of IL-4, IL-10 and TNF-alpha in the patients' PBMC cultures, indicating that they probably have a Th2 type of immune response.

  2. Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Purvina, Maija; Hoste, Astrid; Rossignol, Jean-Michel [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France); Lagaudriere-Gesbert, Cecile, E-mail: cecile.lagaudriere-gesbert@u-psud.fr [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer P20, precursor of the HBeAg, interacts with the cellular protein gC1qR. Black-Right-Pointing-Pointer HBeAg and P20 bind to T cell surface and inhibit mitogen-induced T cell division. Black-Right-Pointing-Pointer HBeAg and P20 inhibition of T cell proliferation is gC1qR and IL-1RAcP-independent. -- Abstract: The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).

  3. NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation.

    Science.gov (United States)

    Tan, Lei; Zhang, Yuqiang; Qiao, Changtao; Yuan, Yanmei; Sun, Yingjie; Qiu, Xusheng; Meng, Chunchun; Song, Cuiping; Liao, Ying; Munir, Muhammad; Nair, Venugopal; Ding, Zhuang; Liu, Xiufan; Ding, Chan

    2018-02-23

    Newcastle disease virus (NDV) causes major economic losses in the poultry industry. Previous studies have shown that NDV utilizes different pathways to infect various cells, including dendritic cells (DCs). Here, we demonstrate that NDV gains entry into DCs mainly via macropinocytosis and clathrin-mediated endocytosis. The detection of cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-4 (IL-4) and interleukin-10 (IL-10) indicates that NDV significantly induces Th1 responses and lowers Th2 responses. Furthermore, NDV entry into DCs resulted in the upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and cleaved caspase-3 proteins, which in turn activated the extrinsic apoptosis pathway and induced DCs apoptosis. Transwell® co-culture demonstrated that direct contact between live NDV-stimulated DCs and T cells, rather than heated-inactivated NDV, inhibited CD4 + T cell proliferation. Taken together, these findings provide new insights into the mechanism underlying NDV infections, particularly in relation to antigen presentation cells and suppression of T cell proliferation. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  5. Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy.

    Science.gov (United States)

    Jiruska, Premysl; Shtaya, Anan B Y; Bodansky, David M S; Chang, Wei-Chih; Gray, William P; Jefferys, John G R

    2013-06-01

    Temporal lobe epilepsy alters adult neurogenesis. Existing experimental evidence is mainly from chronic models induced by an initial prolonged status epilepticus associated with substantial cell death. In these models, neurogenesis increases after status epilepticus. To test whether status epilepticus is necessary for this increase, we examined precursor cell proliferation and neurogenesis after the onset of spontaneous seizures in a model of temporal lobe epilepsy induced by unilateral intrahippocampal injection of tetanus toxin, which does not cause status or, in most cases, detectable neuronal loss. We found a 4.5 times increase in BrdU labeling (estimating precursor cells proliferating during the 2nd week after injection of toxin and surviving at least up to 7days) in dentate gyri of both injected and contralateral hippocampi of epileptic rats. Radiotelemetry revealed that the rats experienced 112±24 seizures, lasting 88±11s each, over a period of 8.6±1.3days from the first electrographic seizure. On the first day of seizures, their duration was a median of 103s, and the median interictal period was 23min, confirming the absence of experimentally defined status epilepticus. The total increase in cell proliferation/survival was due to significant population expansions of: radial glial-like precursor cells (type I; 7.2×), non-radial type II/III neural precursors in the dentate gyrus stem cell niche (5.6×), and doublecortin-expressing neuroblasts (5.1×). We conclude that repeated spontaneous brief temporal lobe seizures are sufficient to promote increased hippocampal neurogenesis in the absence of status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Massimo Giuliani

    Full Text Available Human bone marrow mesenchymal stem cells (BM-MSC are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK cells, Dendritic Cells (DC, and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb, cyclins A and D1, as well as up-regulating p27(kip1 expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low/CD8(low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.

  7. Progesterone-induced secretion of dipeptidyl peptidase-IV (cluster differentiation antigen-26) by the uterine endometrium of the ewe and cow that costimulates lymphocyte proliferation.

    Science.gov (United States)

    Liu, W J; Hansen, P J

    1995-02-01

    Dipeptidyl peptidase-IV (DPPIV) is a serine proteinase widely distributed in mammalian tissues, including lymphocytes, where it is identical to the T-cell activation antigen, cluster differentiation antigen-26. In the present study, DPPIV enzymatic activity was found in uterine secretions of unilaterally pregnant ewes in increasing amounts as gestation progressed. Progesterone increased DPPIV in uterine secretions from ovariectomized ewes and cows. DPPIV was enriched from ovine uterine secretions by a combination of cation exchange, gel filtration, lectin, and Gly-Pro-NH2 affinity chromatographies. The mol wt was 107 kilodaltons, as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, and 140 kilodaltons by gel filtration. The pI was estimated to be 6.8. Enzymatic activity had a pH optimum of 8.3 and a Km of 0.32 mM. The sequence of the 34 N-terminal amino acids was 77-87% homologous to an internal region of human cluster differentiation antigen-26 and rat liver DPPIV. Thus, uterine DPPIV appears to be missing the signal sequence that allows integration into the cytoplasmic membrane. DPPIV was localized immunohistochemically to lumenal and glandular endometrial epithelial cells and, in some pregnant ewes, discrete endometrial stromal cells. Highly enriched sheep uterine DPPIV costimulated proliferation of mitogen-treated sheep lymphocytes. Stimulation occurred in the presence of the uterine milk proteins, a pair of progesterone-induced endometrial secretory proteins with well characterized lymphocyte inhibitory activity. However, uterine milk proteins did not inhibit the costimulatory effect of DPPIV on phytohemagglutinin-L stimulated-lymphocyte proliferation. In conclusion, the uterine endometrium synthesizes a biologically active form of DPPIV under the influence of progesterone that is capable of enhancing mitogen-stimulated T-lymphocyte proliferation.

  8. Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro.

    Directory of Open Access Journals (Sweden)

    Lynn B Williams

    Full Text Available Multipotent mesenchymal stromal cells (MSC are receiving increased attention for their non-progenitor immunomodulatory potential. Cryopreservation is commonly used for long-term storage of MSC. Post-thaw MSC proliferation is associated with a lag-phase in vitro. How this lag-phase affect MSC immunomodulatory properties is unknown. We hypothesized that in vitro there is no difference in lymphocyte suppression potential between quick-thawed cryopreserved equine cord blood (CB MSC immediately included in mixed lymphocyte reaction (MLR and same MSC allowed post-thaw culture time prior to inclusion in MLR. Cryopreserved CB-MSC from five unrelated foals were compared using two-way MLR. For each of the five unrelated MSC cultures, paired MLR assays of MSC allowed five days of post-thaw culture and MSC included in MLR assay immediately post-thawing were evaluated. We report no difference in the suppression of lymphocyte proliferation by CB-MSC that had undergone post-thaw culture and MSC not cultured post-thaw (p<0.0001. Also, there was no inter-donor variability between the lymphocyte suppressive properties of MSC harvested from the five different donors (p = 0.13. These findings suggest that cryopreserved CB-MSC may have clinical utility immediately upon thawing. One implication hereof is the possibility of using cryopreserved CB-MSC at third party locations without the need for cell culture equipment or competencies.

  9. β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Yunhui Du

    Full Text Available Autoantibodies against the second extracellular loop of the β(1-adrenergic receptor (β(1-AA not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β(1-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β(1-AA isolated from the sera of dilated cardiomyopathy (DCM patients caused the proliferation of T cells and the secretion of cytokines.Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β(1-AA was detected using ELISA. The CD3(+T lymphocytes were selected separately through flow cytometry and the effect of β(1-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK.β(1-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β(1-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β(1-AA. β(1-AA also inhibited the secretion of interferon-γ (IFN-γ while promoting an increase in interleukin-4 (IL-4 levels.These results demonstrate that β(1-AA isolated from DCM patients binds to β(1-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1-AR/cAMP/PKA and p38 MAPK pathways.

  10. Effects of an illicit cocktail on serum immunoglobulins, lymphocyte proliferation and cytokine gene expression in the veal calf

    International Nuclear Information System (INIS)

    Cantiello, Michela; Carletti, Monica; Cannizzo, Francesca T.; Nebbia, Carlo; Bellino, Claudio; Pie, Sandrine; Oswald, Isabelle P.; Bollo, Enrico; Dacasto, Mauro

    2007-01-01

    At the European Union level, the use of growth promoters (GPs) in cattle and other food-producing species is forbidden; nonetheless, the illicit use of anabolic hormones, β-agonists and corticosteroids, often administered in cocktails at lower concentrations to overcome control procedures, is still of public concern. The immune system (IS) is a multicomponent system that provide a coordinated response toward infectious diseases, not self-neoplasms and xenobiotics; in this respect, some GPs have been proved able to cause both morphological alterations in lymphoid organs and a modulating effect upon some immunological parameters. Therefore, in the present study the effects of an illicit cocktail upon the cattle IS functions were investigated by using some common endpoints adopted for the IS testing in humans. Twelve cross-bred male veal calves were divided in two experimental groups (n = 6); the first group was administered a cocktail of 17β-oestradiol (10 mg, 3 im injections at 17 days intervals), clenbuterol (20 μg kg -1 , per os for 40 days) and dexamethasone (4 mg per os for 6 days and, then, 5 mg for further 6 days) for a total of 55 days. The second one was used as control. Blood sampling were taken at T 0 and after 15 (T 1 ), 34 (T 2 ), 48 (T 3 ) days as well as the day before slaughtering (T 4 ). Immune endpoints considered were the thymus weight, the serum immunoglobulin G (IgG) and M (IgM) levels, the lymphocyte proliferation assay and the lymphocyte interleukins 1β and 8, tumour necrosis factor α and interferon γ (IFN-γ) gene expression levels. The administration of the illicit cocktail resulted in: (a) a reduction (P 1 , whereas in the second part of the study increasing levels (P 2 and T 4 for IgM and IgG, respectively) were recorded; (c) an overall reduction (P 1 ; in phytohaemagglutinin-stimulated cells, such a decrease was delayed up to T 2 (P 1 and T 2 . Taken together, present data suggest that GPs, even given in cocktails at sub

  11. Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation

    Science.gov (United States)

    Gantner, Florian; Götz, Christine; Gekeler, Volker; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

    1998-01-01

    CD19+ B lymphocytes were purified from the peripheral blood of normal and atopic subjects to analyse and compare the phosphodiesterase (PDE) activity profile, PDE mRNA expression and the importance of PDE activity for the regulation of B cell function.The majority of cyclic AMP hydrolyzing activity of human B cells was cytosolic PDE4, followed by cytosolic PDE7-like activity; marginal PDE3 activity was found only in the particulate B cell fraction. PDE1, PDE2 and PDE5 activities were not detected.By cDNA-PCR analysis mRNA of the PDE4 subtypes A, B (splice variant PDE4B2) and D were detected. In addition, a weak signal for PDE3A was found.No differences in PDE activities or mRNA expression of PDE subtypes were found in B cells from either normal or atopic subjects.Stimulation of B lymphocytes with the polyclonal stimulus lipopolysaccharide (LPS) induced a proliferative response in a time- and concentration-dependent manner, which was increased in the presence of interleukin-4 (IL-4). PDE4 inhibitors (rolipram, piclamilast) led to an increase in the cellular cyclic AMP concentration and to an augmentation of proliferation, whereas a PDE3 inhibitor (motapizone) was ineffective, which is in accordance with the PDE profile found. The proliferation enhancing effect of the PDE4 inhibitors was partly mimicked by the cyclic AMP analogues dibutyryl (db) cyclic AMP and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3′,5′-cyclic monophosphorothioate, Sp-isomer (dcl-cBIMPS), respectively. However, at concentrations exceeding 100 μM db-cyclic AMP suppressed B lymphocyte proliferation, probably as a result of cytotoxicity. Prostaglandin E2 (PGE2, 1 μM) and forskolin (10 μM) did not affect B cell proliferation, even when given in combination with rolipram.Inhibition of protein kinase A (PKA) by differentially acting selective inhibitors (KT 5720, Rp-8-Br-cyclic AMPS) decreased the proliferative response of control cells and reversed the proliferation enhancing effects

  12. Results of The Analysis of The Blood Beryllium Lymphocyte Proliferation Test Data From The Oak Ridge Y-12 Study

    Energy Technology Data Exchange (ETDEWEB)

    Frome, EL

    2001-12-18

    The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. Newman [18] has discussed the clinical significance of the BeLPT and described a standard protocol that was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a ''stimulation index'' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the stimulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were considered in the early 1990's by Frome et al. [7]. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. The purposes of this report are to further evaluate the LAV method using new data, and to describe a new method for identification of an abnormal or borderline test. This new statistical biological positive (SBP) method reflects the clinical judgment that (1) at least two SIs show a ''positive'' response to beryllium, and (2), that the maximum of the six SIs must exceed a cut point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 facility in Oak Ridge and consist of 1080 worker and 33 nonexposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86

  13. Immature dendritic cells generated from cryopreserved human monocytes show impaired ability to respond to LPS and to induce allogeneic lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Guilherme Ferreira Silveira

    Full Text Available Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs, the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

  14. [Roles of interleukin-10 differentiated dendritic cell of allergic asthma patients in T-lymphocyte proliferation in vitro].

    Science.gov (United States)

    Tang, Jian-feng; Guan, Shu-hong; Wang, Zhi-gang

    2012-10-30

    To explore the roles of interleukin (IL)-10 differentiated peripheral blood monocyte-derived dendritic cell (DC-10) of allergic asthma patients in T-lymphocytes proliferation in vitro. From January to June 2011, 10 subjects with dust mite allergic asthma treated at Third Affiliated Hospital of Soochow University were enrolled. Their peripheral blood monocytes were isolated by Ficoll-Hypaque solution density gradient centrifugation and adherent method. And the adherent monocytes were routinely cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF)+interleukin-4 (IL-4)+tumor necrosis factor-alpha (TNF-α), stimulated with/without interleukin-10 (IL-10), pulsed with dust mite allergen and finally harvested. The cell surface molecules including CD80, CD83, CD86, human leukocyte antigen (HLA)-DR and immunoglobulin-like transcript 2 (ILT2) were detected by immunofluorescent labeling and flow cytometry. And cellular functions were estimated by detecting the capacities of DC uptake antigens with fluorescein isothiocyanate (FITC)-dextran capturing assay. The IL-10 differentiation DC (DC-10) were cultured with autologous peripheral T cells (DC-10 group), either alone (DC-TNF group) or together (combined group) with autologous immunostimulatory DC (DC-TNF). And the impact of this treatment on T-cell responses was assessed for each donor by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay. The production of interferon-γ (IFN-γ), IL-4, interleukin-5 (IL-5) and interleukin-13 (IL-13) were measured with the quantification of enzyme linked immunosorbent assay (ELISA) kits. In DC-10, the levels of some mature DC's markers (CD80, CD83, CD86 & HLA-DR) decreased, ILT2 increased and there were the higher capacities of up-taking FITC-dextran particle (72.32%±2.93% vs 54.41%±2.95%, PDC-10 group (1.06±0.18) and that of the combined group (1.34±0.16) were significantly inhibited (PDC-10 group versus (3223±203), (149±19), (2465±183) and

  15. Optimized choice of method for determining proliferation response of peripheral lymphocytes to mitogens in low dose irradiation with cyclotron fast neutrons

    International Nuclear Information System (INIS)

    Refka, Z.; Svec, M.; Aganov, P.; Svoboda, V.; Podzimek, F.

    1989-01-01

    Heparinized venous blood sampled from seven donors was irradiated with doses of 0.1; 0.25; 0.5; 1.0; 2.0 and 3.0 Gy of fast neutrons of a mean energy of 7.6 MeV using the U 120 M isochronous cyclotron. A non-irradiated control sample was also prepared. A lymphoblastic transformation test was conducted with both the intact and irradiated samples. The samples were cultivated in the RPMI-1640 medium with and without a mitogen addition, this in five time variants, viz., for 48, 72, 90, 96 and 120 hours. The proliferation was monitored of lymphocytes stimulated with mitogens PHA, CON-A and PWM in dependence on the time of cultivation and on the radiation dose. The dose dependent relative response was also studied of the irradiated lymphocytes. (E.J.). 8 figs., 1 tab., 18 refs

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  17. 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

  18. Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

    Directory of Open Access Journals (Sweden)

    Sha-Sha Huang

    2016-10-01

    Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

  19. Regulatory T cells generated during cytomegalovirus in vitro stimulation of mononuclear cells from HIV-infected individuals on HAART correlate with decreased lymphocyte proliferation

    International Nuclear Information System (INIS)

    Jesser, Renee D.; Li, Shaobing; Weinberg, Adriana

    2006-01-01

    HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, we studied the phenotype and function of in vitro cytomegalovirus (CMV)-stimulated T cells from HAART recipients. CFSE-measured proliferation showed CD4 + and CD8 + cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from HAART recipients had lower 3 H-thymidine incorporation; lower IFNγ and TNFα production; higher CD4 + CD27 - CD28 - and CD8 + CD27 - CD28 - frequencies; lower CD4 + CD25 hi ; and higher FoxP3 expression in CD8 + CD25 hi cells. CMV-specific proliferation correlated with higher IFNγ, TNFα and IL10 levels and higher CD4 + perforin + and CD8 + perforin + frequencies. Decreased proliferation correlated with higher CD4 + CD27 - CD28 - frequencies and TGFβ1 production, which also correlated with each other. Anti-TGFβ1 neutralizing antibodies restored CMV-specific proliferation in a dose-dependent fashion. In HIV-infected subjects, decreased proliferation correlated with higher CMV-stimulated CD8 + CD25 hi frequencies and their FoxP3 expression. These data indicate that FoxP3- and TGFβ1-expressing regulatory T cells contribute to decreased immunity in HAART recipients

  20. Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

    Science.gov (United States)

    Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

    2015-12-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (pe-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers. Copyright © 2015. Published by Elsevier B.V.

  1. [The effect of polymorphism of genes of xenobiotics detoxication on the frequencies of spontaneous and induced chromosome aberrations in human lymphocytes].

    Science.gov (United States)

    Sal'nikova, L E; Akaeva, E A; Elisova, T V; Kuznetsova, G I; Kuz'mina, N S; Vesnina, I N; Lapteva, N Sh; Chumachenko, A G; Romanchuk, V A; Rubanovich, A V

    2009-01-01

    Here presented the data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 97 volunteers depending on genotypes by genes of xenobiotics detoxication before and after gamma-irradiation with dose of 1 Gy in vitro. The frequencies of aberrations were estimated by analyzing not less than 500-1000 metaphases per person. The data of cytogenetic analysis were compared with the results of PCR-genotyping of loci GSTM1, GSTT1, GSTP1, CYP1A1, CYP2D6, NAT2, and MTHFR. The significant differences by the frequencies of aberrations between "single-locus" genotypes were not found except for GSTM1 locus, for which the enhanced frequency of spontaneous aberrations of chromosome type in "positive" genotypes compared to "zero" ones, i.e., homozygotes by deletion (p = 0.04) was observed. The minimum frequency of spontaneous aberrations of chromosome type was recorded for carriers of double homozygotes by deletion of GSTM1-GSTT1: 0.0006 +/- 0.0003 against 0.0027 +/- 0.0003 for the rest of genotypes (p = 0.016 by the Mann-Witney test). The frequency of gamma-induced chromosome aberrations was correlated with the total amount of minor alleles in loci GSTP1, NAT2, and MTHFR (r = 0.25 at p = 0.0065).

  2. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  3. Spontaneous micronucleus frequencies in human peripheral blood lymphocytes as a screening test for an individual variation in a different population and radiation-induced micronucleus induction

    International Nuclear Information System (INIS)

    Kang, Chang-Mo; Jeon, Hye-Jeong; Cho, Chul-Koo

    2004-01-01

    Our studies were to evaluate the role of epigenetic factors in the variation of radiosensitivity on human peripheral blood lymphocytes by measuring the frequencies of micronucleus (MN) from 293 healthy subjects of different population for assessing the radiation health risk in Korea. We analyzed the frequencies of both spontaneous and in vitro 60 Co γ-rays or 50MeV neutron-induced MNs. The frequencies of spontaneous NMs not only vary greatly between individuals, but also working or living areas. The increased levels of cells with spontaneous MNs were observed with an increasing age. The frequencies of spontaneous MNs were significantly higher in females than in males. For both sexes, MN frequency was significantly and positively correlated with age. Age and gender are the most important demographic variables impacting on the MN index. Donors who had ever smoked showed significantly increased frequencies of MNs compared to nonsmokers. The main lifestyle factors influencing the MN index in the subjects are correlated significantly and positively with smoke while measuring the spontaneous frequencies of micronuclei. Therefore, it is evident that with regard to the application of MN assay all future studies to evaluate the association between radiosensitivity and susceptibility for radiation health risks in different populations should take into account the effect of age, gender and lifestyle. For the dose-response study, the induced MNs were observed at all doses, and the numerical changes according to doses. The dose-response curves were fitted with a linear-quadratic forms of the dose, and the results were different for γ-rays and neutrons significantly. Neutrons were more effective than γ-rays in producing MN with a dose-dependent manner. The frequency of MN varies with dose. The RBE for a micronuclei was 2.37 ± 0.17. The results suggested that the MN assay have a high potential to ensure appropriate quality control and a standard documentation protocol, which

  4. Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China

    International Nuclear Information System (INIS)

    Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

    2015-01-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β 2 -MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g −1 , p < 0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g −1 , p > 0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p < 0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p < 0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β 2 -MG (p < 0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p < 0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may

  5. Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Peiwei, E-mail: pwxu@cdc.zj.cn; Lou, Xiaoming; Ding, Gangqiang, E-mail: gqding@cdc.zj.cn; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng, E-mail: zjcdcwxf@gmail.com

    2015-12-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β{sub 2}-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g{sup −1}, p < 0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g{sup −1}, p > 0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p < 0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p < 0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β{sub 2}-MG (p < 0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p < 0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released

  6. [Changes of content and mRNA expression of gelsolin and proliferation activity of T-lymphocyte in spleen of mice with severe burn injury].

    Science.gov (United States)

    Chen, Q; Yang, H M

    2017-08-20

    Objective: To investigate the changes of content and mRNA expression of gelsolin and proliferation activity of T-lymphocyte in spleen of mice with severe burn injury, so as to determine the optimum intervention time of gelsolin. Methods: Eighty male BALB/c mice were divided into sham injury group and burn group according to the random number table, with 40 mice in each group. Mice in burn group were inflicted with 15% total body surface area full-thickness scald (hereinafter referred to as burn) on the back. Immediately after injury, mice in burn group were hypodermic injected with 1 mL normal saline, with iodophor smeared on back once a day to prevent infection. Mice in sham injury group were sham injured without fluid infusion and smearing iodophor. At post injury hour (PIH) 0 (immediately), 8, 24, 48, and 72, spleen of 8 mice of each group were harvested aseptically, respectively. Proliferation activity of T-lymphocyte was determined with methyl-thiazolyl-tetrazolium colorimetry method; gelsolin content of spleen was determined with enzyme-linked immunosorbent assay; mRNA expression of gelsolin of spleen was determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with analysis of variance of factorial design, one-way analysis of variance, LSD test and Bonferroni correction. Results: (1) There was no significant difference in proliferation activity of T-lymphocyte in spleen of mice in two groups at PIH 0 ( P >0.05). Proliferation activity of T-lymphocyte in spleen of mice in sham injury group was significantly higher than that in burn group at PIH 8, 24, 48, and 72 (with P values below 0.05). There was no significant difference in proliferation activity of T-lymphocyte in spleen of mice in sham injury group at each time point post injury ( F =0.756, P >0.05). Proliferation activity of T-lymphocyte in spleen of mice in burn group at PIH 8 was 0.12±0.04, significantly lower than that at PIH 0, 24, 48

  7. IL-6, in synergy with IL-7 or IL-15, stimulates TCR-independent proliferation and functional differentiation of CD8+ T lymphocytes.

    Science.gov (United States)

    Gagnon, Julien; Ramanathan, Sheela; Leblanc, Chantal; Cloutier, Alexandre; McDonald, Patrick P; Ilangumaran, Subburaj

    2008-06-15

    Recent reports have shown that IL-21, in synergy with IL-15, stimulates proliferation of CD8(+) T lymphocytes in the absence of signaling via the TCR. In this study, we show that IL-6, which induces phosphorylation of STAT3 similarly to IL-21, also can stimulate proliferation of CD8(+) T cells in synergy with IL-7 or IL-15. IL-6 displays a stronger synergy with IL-7 than with IL-15 to stimulate naive CD8(+) T cells. Concomitant stimulation by IL-6 or IL-21 augments phosphorylation and DNA-binding activity of STAT5 induced by IL-7 or IL-15. Like IL-21, IL-6 reduces the TCR signaling threshold required to stimulate CD8(+) T cells. Prior culture of P14 TCR transgenic CD8 T cells with IL-6 or IL-21 in the presence of IL-7 or IL-15 augments their proliferation and cytolytic activity upon subsequent stimulation by Ag. Furthermore, cytokine stimulation induces quantitatively and qualitatively distinct phenotypic changes on CD8(+) T cells compared with those induced by TCR signaling. We propose that the ability of IL-6 to induce TCR-independent activation of CD8(+) T cells in synergy with IL-7 or IL-15 may play an important role in the transition from innate to adaptive immunity.

  8. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  9. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  10. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sung, Jin Young; Choi, Hyoung Chul

    2011-01-01

    Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  11. Phytohemagglutinin induced proliferation by aged lymphocytes: reduced expression of high affinity interluekin-2 receptors and interleukin-2 secretion

    International Nuclear Information System (INIS)

    Froelich, C.J.; Burkett, J.S.; Guiffaut, S.; Kingsland, R.; Brauner, D.

    1988-01-01

    Human lymphocytes from elderly and young donors were cultured with phytohemagglutinin. Cultures from two groups of aged donors, recruited respectively from the authors ambulatory clinic and a nursing home, incorporated less tritiated thymidine ( 3 H-TdR) and secreted less interleukin-2 than did young donors. Furthermore, as determined for the first time by a radioligand binding receptor assay, the aged lymphoblasts possessed significantly fewer high affinity IL-2 receptors per cell. Despite a decrease in the number of high affinity receptor cells the dissociation constant (Kd) was comparable for the three groups. It was also shown that the amounts of soluble IL-2 receptors that were released into the supernatants by mitogen stimulated cells did not differ for the aged and young donors. These data suggest that defects in IL-2 production and high affinity IL-2 receptor generation may both be responsible for immune deficiency in the elderly

  12. The improvement effects of edible bird’s nest on proliferation and activation of B lymphocyte and its antagonistic effects on immunosuppression induced by cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Zhao R

    2016-01-01

    Full Text Available Ran Zhao,1,* Geng Li,1,* Xiu-juan Kong,1 Xiu-yan Huang,2 Wei Li,1 Yao-ying Zeng,2 Xiao-ping Lai31Traditional Chinese Medicinal College, Guangzhou University of Chinese Medicine, 2Life Science College, Jinan University, Guangzhou, 3Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, People’s Republic of China*These authors contributed equally to this workAbstract: Edible bird’s nest (EBN is regarded as an immune-enhancing food in the People’s Republic of China. The aim of this study is to demonstrate the efficiency of EBN in improving the immunity of mouse both in vivo and in vitro. We observed the effects of EBN on spleen lymphocytes proliferation and activation, as well as immunoglobulin isotypes as indicators. In addition, we evaluated the content of total sIgA in the intestinal juice to assess mucosal immunity. The results showed that EBN could promote the proliferation and activation of B-cells and increase IgE, IgA, IgM, and IgG3 levels. We also found that EBN extract can promote the secretion of sIgA in the small intestine. Using cyclophosphamide (CY, we established an immunosuppressed mouse model in which we identified a reversal influence on the ratio of CD3+/CD19+ cells, which indicates that EBN also protects B-cells from the damage induced by CY. We also applied polymyxin B to exclude the interference of lipopolysaccharide throughout the experiment. In conclusion, we found that EBN can reduce the intestinal immune injury induced by CY by accelerating the proliferation and activation of B-cells and enhancing antibody secretion of B-cells.Keywords: chemotherapy, immunological enhancement, intestinal mucosal immune, EBN

  13. Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals

    DEFF Research Database (Denmark)

    Theander, T G; Bygbjerg, I C; Jepsen, S

    1986-01-01

    -immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg...... and that this activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when...

  14. Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy

    Czech Academy of Sciences Publication Activity Database

    Jiruška, Přemysl; Shtaya, A.B.Y.; Bodansky, D.M.S.; Chang, W.C.; Gray, W.P.; Jefferys, J. G. R.

    2013-01-01

    Roč. 54, Jun 2013 (2013), s. 492-498 ISSN 0969-9961 R&D Projects: GA ČR(CZ) GAP303/10/0999 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : spontaneous seizures * temporal lobe epilepsy * neurogenesis * tetanus toxin * apoptosis Subject RIV: FH - Neurology Impact factor: 5.202, year: 2013

  15. Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation.

    Science.gov (United States)

    Boulland, Marie-Laure; Marquet, Jeanine; Molinier-Frenkel, Valérie; Möller, Peter; Guiter, Chrystelle; Lasoudris, Fanette; Copie-Bergman, Christiane; Baia, Maryse; Gaulard, Philippe; Leroy, Karen; Castellano, Flavia

    2007-07-01

    Interleukin-4-induced gene 1 (IL4I1) was first described as a B-cell IL4-inducible gene and is highly expressed in primary mediastinal B-cell lymphomas. We established stable HEK293 clones expressing human and mouse IL4I1 to examine their biochemical properties and function. Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1. We showed that IL4I1 has l-amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine. Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigen-presenting cell/T-lymphocyte cross-talk. Indeed, hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4(+) and CD8(+) T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H(2)O(2) than naive T cells. hIL4I1 inhibitory effect was dependent on enzymatic activity and H(2)O(2) production and associated with a transient down-regulation of TCRzeta expression. Altogether these data suggest IL4I1 as a new immunomodulatory enzyme produced by DCs.

  16. Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer.

    Science.gov (United States)

    Shichijo, Shigeki; Azuma, Kouichi; Komatsu, Nobukazu; Ito, Masaaki; Maeda, Yoshiaki; Ishihara, Yuki; Itoh, Kyogo

    2004-09-01

    The purpose of this work was to provide a scientific basis for specific immunotherapy of colon cancer. This study focused on identification of colon tumor-associated antigens and HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs) generated from tumor-infiltrating lymphocytes of a colon cancer patient. A gene expression cloning method was used to identify genes coding for tumor antigens. Fifty-six peptides with HLA-A2-binding motifs encoded by these proteins were examined for their ability to induce HLA-A2-restricted and tumor-reactive CTLs. We identified the following three genes coding for proliferation-related proteins: thymidylate synthase (TYMS), which is involved in chemoresistance (5-fluorouracil); 5'-aminoimidazole-4-carboxamide-1-beta-d-ribonucleotide transfolmylase/inosinicase (AICRT/I); and phosphoglycerate kinase 1 (PKG1), which was secreted by tumor cells and involved in the angiogenic process. TYMS was preferentially expressed in tumor cells, whereas AICRT/I and PKG1 were equally expressed in both cancer cells and normal tissues at the mRNA level. Among 56 peptides with HLA-A2-binding motifs encoded by these proteins, 8 peptides were recognized by the CTLs, and 5 of 8 peptides were also recognized by the CTL precursors without ex vivo activation in the peripheral blood of colon cancer patients. Furthermore, four of them (one each from TYMS and PKG1 and two from AICRT/1) possessed the ability to induce HLA-A2-restricted and peptide-specific CTLs cytotoxic to colon tumor cells in peripheral blood mononuclear cells of colon cancer patients. TYMS and PGK1, as well as their epitope peptides, might be appropriate target molecules for specific immunotherapy of HLA-A2(+) colon cancer patients because of the positive role of TYMS and PGK1 in chemoresistance (5-fluorouracil) and angiogenesis of tumor cells, respectively.

  17. Analysis of T lymphocyte subsets proliferating in response to infective and UV-inactivated African swine fever viruses.

    Science.gov (United States)

    Canals, A; Alonso, F; Tomillo, J; Domínguez, J

    1992-11-01

    The proliferative response to infective and UV-inactivated African swine fever virus was analyzed in cells from pigs surviving an experimental infection with attenuated virus. All the pigs showed strong dose-dependent proliferative responses to both infective and UV-inactivated virus. This response was also observed when nitrocellulose-bound solubilized virus proteins were used in the assay. Heterologous isolates also induced proliferation, however it was significantly lower than that induced by the isolate used to infect the animals. The response to infective virus was blocked equally by anti-CD4 and anti-CD8 monoclonal antibodies (mAb); the response to UV-inactivated virus was almost abolished by anti-CD4 and 60% inhibited by anti-CD8 mAb. FACS analysis of 28-day T cell lines derived from peripheral blood mononuclear cells demonstrated the progressive increase of the CD8+ subset when the cells were stimulated with infective virus, whereas the stimulation with UV-inactivated virus induced the increase of both CD4+ and CD8+ subsets. In this case, the sum of CD4+ and CD8+ percentages was higher than the total percentage of T cells, suggesting the presence of cells positive for both CD4+ and CD8+.

  18. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats

    Directory of Open Access Journals (Sweden)

    Yanru Sun

    2018-02-01

    Full Text Available Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL, which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs. We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  19. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats.

    Science.gov (United States)

    Sun, Yanru; Han, Mingfeng; Shen, Zhenhuang; Huang, Haibo; Miao, Xiaoqing

    2018-02-01

    Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  20. Stimulation of AIDS lymphocytes with calcium ionophore (A23187) and phorbol ester (PMA): studies of cytoplasmic free Ca, IL-2 receptor expression, IL-2 production, and proliferation

    DEFF Research Database (Denmark)

    Hofmann, B; Moller, J; Langhoff, E

    1989-01-01

    . The production of IL-2 in normal lymphocytes stimulated with A23187/PMA was 33 times higher than that after stimulation with PHA. In AIDS lymphocytes the production of IL-2 induced by all activators was severely decreased compared to control subjects, although the production of IL-2 after stimulation with A23187...

  1. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  2. Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide

    DEFF Research Database (Denmark)

    Röpke, M; Hald, J; Guldberg, Per

    1996-01-01

    A cytotoxic T lymphocyte (CTL) clone generated in vitro from the peripheral blood of a healthy HLA-A2-positive individual against a synthetic p53 protein-derived wild-type peptide (L9V) was shown to kill squamous carcinoma cell lines derived from two head and neck carcinomas, which expressed muta...

  3. Evaluation of hemocomponents irradiators in the Banco de Sangre of the Hospital Mexico by means of rate determination of the hemolysis and of the proliferation lymphocyte

    International Nuclear Information System (INIS)

    Quiros Barrantes, S.; Rodriguez Amador, F.

    2003-01-01

    The graft disease versus inn-keeper associated to transfusion (EIVH AT) happens with the transfusion of viable lymphocytes to a allogeneic recipient, which is unable to produce an immune effective response against the graft. The irradiation range of the hemocomponents, to dose of 2500 cGy, eliminates the proliferative capacity of the lymphocyte. In Costa Rica, the irradiated transfusional component has been assumed as an assurance for the patient, though the process unactivation lymphocyte by irradiation has never been evaluated. This research tries to evaluate the efficiency of the process of irradiation of hemocomponents of the Banco de Sangre del Hospital Mexico, with preventive purposes of EIVH AT, and also, to determine if this process alters in an immediate way the erythrocyte component. (Author) [es

  4. Suppressor cell hyperactivity relative to allogeneic lymphocyte proliferation as a manifestation of defective T-T-cell interactions in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Stenina, M.A.; Potapova, A.A.; Biryukov, A.V.; Skripnik, A.Yu.; Cheredeev, A.N.

    1987-01-01

    The authors study the state of immunoregulatory process in patients with systemic lupus erythematosus at the T-T-cell interaction level and seek to test the possibility of the pharmacological modulation of this process. The proliferative activity of mononuclear lymphocytes, extracted from the blood of ten lupus patients, was assessed by measuring the incorporation of tritiated thymidine into cultures stimulated by phytohemagglutinin, concanavalin, and theophylline. The comparative effects of each of these agents on the immunoregulatory and proliferative activity of the lymphocytes are reported

  5. Evaluation of the potential immunotoxicity of 3-monochloro-1,2-propanediol in Balb/c mice I. Effect on antibody forming cell, mitogen-stimulated lymphocyte proliferation, splenic subset, and natural killer cell activity

    International Nuclear Information System (INIS)

    Lee, Jong Kwon; Byun, Jung A.; Park, Seung Hee; Kim, Hyung Soo; Park, Jae Hyun; Eom, Juno H.; Oh, Hye Young

    2004-01-01

    3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. However, no previous studies have investigated MCPD-induced alterations in the immune system. In the present study, MCPD was administered by gavage for 14 days at 0, 25, 50, and 100 mg/kg per day to female Balb/c mice. The antibody-mediated immune response to sheep red blood cells (SRBC) was assessed using the antibody-forming cell (AFC) assay, and splenic cell phenotypes were quantified by flow cytometry. Hematological and histopathological changes were assessed. Mitogen-stimulated spleen lymphocyte proliferation and natural killer (NK) cell activity were evaluated. The T-lymphocyte blastogenesis by concanavalin A (Con A) or anti-CD3 and B-lymphocyte blastogenesis by lipopolysaccharide (LPS) were not significantly changed. There were no significant changes in the hematological and histopathological findings of MCPD-treated mice. However, the significant decrease in thymus weight was observed in 100 mg dose group, even though that did not change body weight gain. The cellularities of spleen and thymus were significantly reduced in high-dose group. Exposure to high dose of MCPD decreased the AFC response to SRBC in mice. There was a significant decrease in NK cell activity of mice treated with high dose of MCPD. These results indicate that MCPD could modulate the immune function in Balb/c mice

  6. Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes

    NARCIS (Netherlands)

    Finlay, D.K.; Sinclair, L.V.; Feijoo, C.; Waugh, C.M.; Hagenbeek, T.J.; Spits, H.; Cantrell, D.A.

    2009-01-01

    In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)-mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study

  7. The Effects of (99mTc Hm-Pao Labeling on Lymphocyte Functions

    Directory of Open Access Journals (Sweden)

    Özden Ülker

    2016-01-01

    Full Text Available Objective: (99mTc HM-PAO labeled leucocytes have been used as a standard diagnostic procedure for the detection of infection and inflammation. Although, some investigators have already pointed out that labeling of leucocytes with (99mTc HM-PAO has detrimental effects on the cells, still very little is known regarding the effects of ionizing radiation on lymphocyte functions. Methods: In this study, we evaluated the effects of (99mTc HM-PAO labeling on lymphocyte adhesion, proliferation, migration and apoptosis. We used NC-NC lymphoblastoid cell line as the lymphocyte population. (99mTc HM-PAO labeling decreased cell adhesion, proliferation and motility whereas induced apoptosis, and cell cycle arrest. Proliferation assays were performed both using MTT and ELISA tests with 24 hours intervals following labeling. Results: It was recorded that the rate of decrease in proliferation was up to 70% by the 4th day after labeling. (99mTc HMPAO labeling led a 35% decrease on adhesion ability of the cells on fibronectin. By using Boyden chamber motility assay, we showed that both spontaneous and MCP-1 induced lymphocyte motility were potently blocked by (99mTc HM-PAO labeling. The rate of decrease in motility was approximately five times. In addition, we observed a 12 times increase in the apoptosis rate within the (99mTc HM-PAO treated cells compared to the control cells. Besides it was observed that cell cycle arrest was induced starting from 3rd day after (99mTc HM-PAO treatment. Conclusion: Based on our data (99mTc HM-PAO labeling has damaging effects on lymphocyte functions including cell adhesion, proliferation, motility and viability in in vitro

  8. Heterogeneity of chromosome damage in [beta]-thalassaemia traits. An evaluation of spontaneous and [gamma]-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G[sub 0] and G[sub 2] phase irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaja, A.P.; Sharma, N.K. (Bhabha Atomic Research Centre, Bombay (India). Molecular Biology and Agriculture Div.)

    1994-07-01

    This study is an attempt to evaluate the chromosomal radiosensitivity of [beta]-thalassaemia traits compared with healthy individuals from the general population, necessitated by the fact that [beta]-thalassaemia trait is present in 1-17% of different population groups in India and the chances of encountering them in radiation and chemical related industries do exist. Spontaneous chromosome aberration frequencies in peripheral blood lymphocytes from [beta]-thalassaemia traits were found to be in the normal range, whereas significantly higher frequencies of micronuclei (MN) were observed in thalassaemia traits. Based on MN frequency at 2 Gy, [beta]-thalassaemia traits fall into two distinct categories. A hypersensitive group with significant increase in radiation-induced MN over the control group, and a second group with MN frequency slightly above normal individuals. Even when compared with the fitted data at 2 Gy obtained from the pooled results of extensive dose-response investigations from 0.5-5 Gy [gamma]-rays with normal donors for MN, dicentrics and total aberrations, the difference between the means of MN frequencies in [beta]-thalassaemia traits and normals is significant. (author).

  9. Artesunate influences Th17/Treg lymphocyte balance by modulating Treg apoptosis and Th17 proliferation in a murine model of rheumatoid arthritis

    Science.gov (United States)

    Liu, Jia; Hong, Xuezhi; Lin, Dong; Luo, Xiaohong; Zhu, Mengya; Mo, Hanyou

    2017-01-01

    CD4+ regulatory T (Treg) cells and T-helper 17 (Th17) cells have been shown to have important roles in rheumatoid arthritis (RA). In our previous study, it was demonstrated that artesunate was able to alter the Treg/Th17 ratio in patients with RA; however, the underlying mechanisms remain unclear. The present study established a male Sprague Dawley (SD) rat model of type II collagen-induced arthritis (CIA). SD rats were divided into normal control, CIA model and artesunate-treated (5, 10 or 20 mg/kg/day) groups. Treg and Th17 cells were detected in the synovium by immunohistochemical analysis of forkhead/winged helix transcription factor (Foxp3) and interleukin (IL)-17 expression. Subsequently, lymphocytes were extracted from the rat spleens, and the proportions of Treg/Th17 cells were detected by flow cytometry. The results demonstrated that the expression levels of Foxp3 were significantly decreased, and those of IL-17 were significantly increased, in the CIA model group, as compared with the normal control group. The results demonstrated that artesunate decreased the frequency of Th17 cells and increased the frequency of Treg cells in CIA rats in a dose-dependent manner. In conclusion, the present study suggested that artesunate may regulate the Th17/Treg balance by inducing Th17-mediated apoptosis. Therefore, artesunate may be considered a novel therapeutic agent for the treatment of patients with RA. PMID:28565837

  10. GB virus C infection is associated with altered lymphocyte subset distribution and reduced T cell activation and proliferation in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Jack T Stapleton

    Full Text Available GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART. The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL or cART naïve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38(+/HLA-DR(+, proliferation (Ki-67+, and HIV entry co-receptor expression (CCR5+ and CXCR4+ on total CD4+ and CD8+ T cells, and on naïve, central memory (CM, effector memory (EM, and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naïve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naïve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.

  11. Rat splenocytes inhibit antigen-specific lymphocyte proliferation through a reactive nitrogen intermediate (RNI)-dependent mechanism and exhibit increased RNI production in response to IFN-gamma.

    Science.gov (United States)

    Stein, C S; Strejan, G H

    1993-09-01

    Rat splenocytes inhibited antigen-specific proliferation of primed lymph node cells in vitro. This inhibition resided in the plastic-adherent splenocyte fraction and was radioresistant, suggesting that the effect was due to macrophages. While this suppression was more evident if spleen cells were derived from immunized rats, spleen cells from normal rats were just as suppressive when added to cocultures at higher numbers. Proliferative responses were greatly enhanced in the presence of NG-monomethyl-L-arginine, a specific inhibitor of the nitric oxide synthetic pathway, and significant levels of nitrite (NO2-), a product of this pathway, were detected in culture supernatants in association with suppressed responses, supporting the notion that suppression was mediated by the L-arginine-dependent production of reactive nitrogen intermediates (RNI). When the splenocytes were physically separated from the responding lymph node cell population, high levels of NO2- were still detected but proliferative responses were no longer inhibited, suggesting that cell proximity or contact is necessary for delivery of the suppressive signal. Adherent splenocytes cultured alone produced low levels of NO2-. Addition of 1 to 50 U/ml IFN-gamma induced a dose-dependent increase in NO2- production, with the maximal level approximating that found in suppressed cocultures; TNF-alpha, IL-2, or LPS did not synergize with IFN-gamma to enhance NO2- production. These findings suggest that by activating macrophages to upregulate RNI synthesis, IFN-gamma-producing T cells may exert a negative influence over their own proliferation.

  12. Rai acts as a negative regulator of autoimmunity by inhibiting antigen receptor signaling and lymphocyte activation.

    Science.gov (United States)

    Savino, Maria Teresa; Ortensi, Barbara; Ferro, Micol; Ulivieri, Cristina; Fanigliulo, Daniela; Paccagnini, Eugenio; Lazzi, Stefano; Osti, Daniela; Pelicci, Giuliana; Baldari, Cosima T

    2009-01-01

    Rai (ShcC) belongs to the family of Shc adaptor proteins and is expressed in neuronal cells, where it acts as a survival factor activating the PI3K/Akt survival pathway. In vivo, Rai protects the brain from ischemic damage. In this study, we show that Rai is expressed in T and B lymphocytes. Based on the finding that Rai(-/-) mice consistently develop splenomegaly, the role of Rai in lymphocyte homeostasis and proliferation was addressed. Surprisingly, as opposed to neurons, Rai was found to impair lymphocyte survival. Furthermore, Rai deficiency results in a reduction in the frequency of peripheral T cells with a concomitant increase in the frequency of B cells. Rai(-/-) lymphocytes display enhanced proliferative responses to Ag receptor engagement in vitro, which correlates with enhanced signaling by the TCR and BCR, and more robust responses to allergen sensitization in vivo. A high proportion of Rai(-/-) mice develop a lupus-like autoimmune syndrome characterized by splenomegaly, spontaneous peripheral T and B cell activation, autoantibody production, and deposition of immune complexes in the kidney glomeruli, resulting in autoimmune glomerulonephritis. The data identify Rai as a negative regulator of lymphocyte survival and activation and show that loss of this protein results in breaking of immunological tolerance and development of systemic autoimmunity.

  13. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

    Science.gov (United States)

    Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2017-03-01

    We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

  14. Transgenic expression of TGF-β on thyrocytes inhibits development of spontaneous autoimmune thyroiditis and increases regulatory T cells in thyroids of NOD.H-2h4 mice

    OpenAIRE

    Yu, Shiguang; Fang, Yujiang; Sharp, Gordon C.; Braley-Mullen, Helen

    2010-01-01

    Transgenic NOD.H-2h4 mice expressing TGF-β under control of the thyroglobulin promoter were generated to address the role of TGF-β in development of thyrocyte hyperplasia. In contrast to non-transgenic (Tg−) littermates which develop lymphocytic spontaneous autoimmune thyroiditis (L-SAT), all TGF-β transgenic (Tg+) mice given NaI water for 2–7 mo develop thyroid lesions characterized by severe thyroid epithelial cell hyperplasia and proliferation (TEC H/P) with fibrosis and less lymphocyte in...

  15. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  16. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  17. Helicobacter pylori Associated Lymphocytic Gastritis in a Child

    OpenAIRE

    Kim, Min Jeong; Eom, Dae Woon; Park, Kieyoung

    2014-01-01

    Lymphocytic gastritis (LG) is a rare subtype of chronic gastritis. It is defined as dense proliferation of intraepithelial lymphocytes (IELs) more than 25 lymphocytes per 100 epithelial cells. The known major causes of LG are celiac disease and Helicobacter pylori infection. H. pylori associated LG (HpLG) has more enhanced cytotoxic and apoptotic tendencies than chronic H. pylori gastritis. A 12-year-old girl with postprandial epigastric pain was diagnosed HpLG on endoscopic biopsy. After the...

  18. 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....

  19. A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2014-01-01

    Full Text Available Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

  20. A non-toxic herbal remedy which enhance lymphocyte activity and ...

    African Journals Online (AJOL)

    In human lymphocytes, G. lucidum was found to significantly increase cell proliferation and metabolism (p<0.05). T lymphocytes also demonstrated aggregation after G. lucidum treatment, which indicated T lymphocyte transformation. G. lucidumtreated cells also demonstrated a significantly increased secretion of IL-2, IL-8 ...

  1. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  2. Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Svenson, M; Theander, T G

    1987-01-01

    Effect of pyrimethamine, an antimalarial antifolate, and of mefloquine, chloroquine, and quinine, which belong to the quinoline group of antimalarials, on proliferation and interleukin 2 (IL-2) production of human lymphocytes was studied in vitro. Pyrimethamine at concentrations above therapeutic...... levels suppressed the lymphocytes' proliferation, but not their IL-2 production. All three quinolines suppressed the proliferation of lymphocytes, but not equally, with mefloquine having the strongest effect. Quinine suppressed the growth at therapeutic concentrations. The IL-2 production was suppressed...... at concentrations twice as high as those required to suppress lymphocyte proliferation. Addition of exogenous IL-2 only partially reversed the suppressive effect on lymphocyte proliferation. Delayed addition of the quinolines decreased their suppressive effect, but not completely. The mechanisms of action on human...

  3. Hsa-miR-15a and Hsa-miR-16-1 Expression Is Not Related to Proliferation Centers Abundance and Other Prognostic Factors in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Maura Rossi

    2013-01-01

    Full Text Available Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL is the commonest leukemia in adults. Here, we aimed to evaluate hsa-miR-15a/hsa-miR-16-1 expression in CLL tissues by qPCR and correlate it with the other clinicopathological features and clinical outcome. 40 formalin-fixed paraffin-embedded (FFPE lymph node samples obtained from CLL/SLL patients were classified into two categories, “PCs rich” and “typical.” We found a significant common expression level of 4 miRNAs; however, we did not find any significant relationship between PCs presence and miRNAs expression. Moreover, neither the presence of 13q deletion nor the percentage of cells carrying the deletion strictly correlated with miRNAs expression levels, although a significant number of patients with 13q deletion presented hsa-miR-16-1-3p levels below the median value in normal samples (P<0.05. Finally, although no correlation was found between the expression of each miRNA and other clinicopathological features (Ki67, CD38, ZAP70, and IGVH@ hypermutations, the OS curves showed a positive trend in patients with miRNAs downregulation, though not statistically significant. In conclusion, we showed for the first time that all miRNAs can be successfully studied in FFPE CLL tissues and that del13q and PCs richness do not strictly correspond to miRNAs downregulation; therefore, a specific evaluation may be envisaged at least in patients enrolled in clinical trials.

  4. Radiation effects on lymphocytes

    International Nuclear Information System (INIS)

    Roser, B.

    1976-01-01

    This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

  5. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    Directory of Open Access Journals (Sweden)

    Hernández-Montes Jorge

    2012-05-01

    Full Text Available Abstract Background Most infections with human papillomavirus (HPV are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL from low-grade squamous intraepithelial lesions (LSIL patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when

  6. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism...

  7. Chronic lymphocytic leukemia: concepts and observations

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.

    1977-01-01

    Thirty-five patients with chronic lymphocytic leukemia (CLL) were studied for assessment of total body leukemic mass and abnormality in T-lymphocyte function associated with clinical stages of CLL. Total body potassium (TBK), an indicator of lean body mass, was found to correlate well with increase in the clinical stage of the disease. Use of TBK for monitoring the regression and relapse of leukemic load is suggested. No correlation was found between whole cell and nuclear volumes of lymphocytes in CLL patients and clinical stages of the disease. Blast transformation and proliferation under phytohemagglutinin (PHA) stimulation appeared to be normal in purified T cells of early stages and abnormal in the late stages of disease.

  8. Labeling with indium-111 has detrimental effects on human lymphocytes: concise communication

    NARCIS (Netherlands)

    ten Berge, R. J.; Natarajan, A. T.; Hardeman, M. R.; van Royen, E. A.; Schellekens, P. T.

    1983-01-01

    When lymphocytes from human peripheral blood were labeled with In-111 oxinate, several of their properties appeared to be affected. The spontaneous release of the radionuclide was found to be relatively high. Labeled lymphocytes showed a decreased proliferative capacity, dependent on the dose of the

  9. Immunosuppressive effect of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the inhibition of T-lymphocyte proliferation and IL-2 production

    International Nuclear Information System (INIS)

    Yun, Cheol-Heui; Son, Chang Gue; Jung, Uhee; Han, Seung Hyun

    2006-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the predominant heterocyclic amine formed in cooked meat and fish and causes cancers in the colon, the mammary glands, and the lymphoid organs. In the present study, we investigated the immunological impact of PhIP using thymocytes isolated from Balb/c mice and a murine thymocyte-derived cell line, EL4. Treatment of the thymocytes with PhIP moderately inhibited T-cell mitogen-induced cell proliferation and interleukin (IL)-2 secretion. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that PhIP attenuated IL-2 mRNA expression in the thymocytes and EL4 cells stimulated with phytohemagglutinin (PHA) plus phorbol 12-myristate 13-acetate (PMA). In vitro transient transfection assay using a reporter gene construct containing IL-2 promoter showed that the decrease in the steady-state IL-2 mRNA level by PhIP is partially due to the attenuation of IL-2 mRNA synthesis at the transcriptional level. Furthermore, an electrophoretic mobility shift assay showed that PhIP inhibited DNA binding activity of nuclear factor for immunoglobulin κ chain in B cells (NF-κB), activator protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT), which are known to be responsible for IL-2 transcriptional activation. Concomitantly, PhIP inhibited the PMA/PHA-induced generation of reactive oxygen species (ROS) involved in activation of the transcription factors. These results suggest that PhIP has potential immunosuppressive effects by inhibiting T-cell proliferation and IL-2 expression through down regulation of ROS generation and thereby inhibiting NF-κB, AP-1 and NF-AT activation

  10. Modeling Adenovirus Latency in Human Lymphocyte Cell Lines ▿ †

    OpenAIRE

    Zhang, Yange; Huang, Wen; Ornelles, David A.; Gooding, Linda R.

    2010-01-01

    Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then decl...

  11. Blood leukocyte and spleen lymphocyte immune response of spleen lymphocytes and whole blood leukocytes of hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Peters, B.A.; Sothmann, M.; Wehrenberg, W.B. (Univ. of Wisconsin, Milwaukee (USA))

    1989-01-01

    This study was designed to evaluate the effects of chronic physical activity on the immune response of spleen lymphocytes and whole blood leukocytes of hamsters. Animals were kept sedentary or allowed to exercise spontaneously on running wheels for eight weeks. Physically active animals averaged 12 kilometers per day. The immune response of spleen lymphocytes whole blood leukocytes was evaluated by {sup 3}H-thymidine incorporation in response to Concanavalin A or lipopolysaccharide. There was no treatment effect between physically active and sedentary hamster in response of spleen lymphocytes. The immune response of whole blood leukocytes to these mitogens was significantly greater in physically active vs. sedentary hamsters. These results demonstrate that chronic physical activity has the capacity to modulate immunoresponses.

  12. T Lymphocytes Inhibit the Vascular Response to Injury

    Science.gov (United States)

    Hansson, Goran K.; Holm, Jan; Holm, Susanna; Fotev, Zisi; Hedrich, Hans-Jurgen; Fingerle, Jurgen

    1991-12-01

    The proliferation of vascular smooth muscle cells is controlled by specific growth factors and cytokines acting in paracrine networks. Macrophage products such as the platelet-derived growth factor and interleukin 1 promote smooth muscle proliferation and are released in the arterial wall during atherosclerosis and repair processes. T lymphocytes are also present in vascular tissue, but their role in vascular growth control in vivo has been unclear. We now demonstrate that rats in which T lymphocytes have been eliminated by a monoclonal antibody develop larger proliferative arterial lesions after balloon-catheter injury. Larger lesions also develop in athymic rnu/rnu rats that lack T lymphocytes, when compared with rnu/+ littermates with normal T-cell levels. Finally, injection of the lymphokine interferon γ inhibits smooth muscle proliferation and results in smaller lesions compared with controls injected with buffer alone. These results indicate that T lymphocytes modulate smooth muscle proliferation during vascular repair. We propose that T lymphocytes may play an important, immunologically nonspecific role in tissue repair processes.

  13. Chromosome instability and global gene expression patterns in proliferating human T-lymphocytes after low dose rate γ-irradiation, and genetic instability in cells from in vivo radiation-exposed persons

    International Nuclear Information System (INIS)

    Holmberg, Kerstin; Faelt, Susann; Wennborg, Anders; Lambert, Bo

    2003-01-01

    Chromosomal instability (Cl), and radiation induced Cl in particular, as well as in a wider sense, genomic instability, has been of great interest lately, as it provides an explanation for the occurrence of multiple mutations during transformation of a normal cell to a malignant tumor cell. To explore this phenomenon, we developed an in vitro system to study the long term, cytogenetic effects of ionizing radiation in human T-lymphocytes. Irradiated or non-irradiated T-cells were grown for up to two months as monoclonal or bulk cell cultures in medium enriched with T-cell growth factors. Analysis of G-banded karyotypes at different time intervals demonstrated clonal aberrations in 65% of the clones derived from irradiated cells, and in only 5% of the clones from non-irradiated cells. Delayed occurrence of de novo aberrations, and a progressive development of subclones with karyotypic abnormalities of increasing complexity, was observed many cell generations after the radiation exposure. Moreover, cells exposed to γ-radiation at a low dose rate (LDR, 0.024 Gy h -1 ) for 5 days in G 0 -phase, e.g. a dose that gives the cells time to repair between subsequent hits, also demonstrated CI. Following a radiological accident in Estonia 1994, we studied the possible induction of CI in vivo. Both long term bulk cultures and single cell clones were established from one high and three low exposed persons, as well as control individuals from Estonia. Compared to our historical Swedish controls, we found CI to occur in both bulk cultures and clones, and the aberrations were more complex in the exposed individuals than in the controls, indicating that the aberrations were caused by the irradiation. However, due to the high frequency of CI in the Estonian controls, no conclusion with regard to chromosomal instability in vivo could be drawn from the study. In order to trace factors that induce and maintain the chromosomal instability, and clarify which steps are affected in the

  14. Does programmed CTL proliferation optimize virus control?

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Thomsen, Allan Randrup

    2005-01-01

    CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferati...

  15. Merkel Cell Carcinoma with Spontaneous Regression: A Case Report and Immunohistochemical Study

    Directory of Open Access Journals (Sweden)

    Hitoshi Terui

    2016-02-01

    Full Text Available Merkel cell carcinoma (MCC is an aggressive neuroendocrine carcinoma that only rarely regresses spontaneously. Since little is known about the immunological mechanisms involved in the spontaneous regression of MCC, we describe a case of MCC with spontaneous regression and employed immunohistochemical staining for cytotoxic and immunosuppressive molecules to investigate possible mechanisms involved in the spontaneous regression of MCC. Interestingly, compared to conventional MCC, tumor-infiltrating lymphocytes in MCC with spontaneous regression contained higher numbers of CD8+ cells and granulysin-bearing cells and lower numbers of CD206+ cells. Our present study suggests one of the possible reasons for the spontaneous regression of MCC.

  16. Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Svenson, M; Theander, T G

    1987-01-01

    Effect of pyrimethamine, an antimalarial antifolate, and of mefloquine, chloroquine, and quinine, which belong to the quinoline group of antimalarials, on proliferation and interleukin 2 (IL-2) production of human lymphocytes was studied in vitro. Pyrimethamine at concentrations above therapeutic...

  17. A non-toxic herbal remedy which enhance lymphocyte activity and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    -aggregation. This study investigates the proliferation, metabolism and cytokine secretion of lymphocytes in vitro upon G. lucidum stimulation. The powder of G. lucidum was provided by Mei Shan Tang Limited (Hong Kong).

  18. Gammadelta lymphocyte response to porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Olin, Michael R; Batista, Laura; Xiao, Zhengguo; Dee, Scott A; Murtaugh, Michael P; Pijoan, Carlos C; Molitor, Thomas W

    2005-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be one of the most important diseases facing swine industry today. Following PRRSV infection pigs develop both humoral and cell-mediated responses following PRRSV exposure; however, the relative importance in protection and clearance of the virus is not yet completely understood. Swine contain a large percentage of gammadelta T-lymphocytes in peripheral circulation capable of responding to various pathogens in both an innate and specific immune response. The objectives of this study were to determine whether gammadelta lymphocytes functionally respond to PRRSV upon initial exposure and re-exposure. Four month old PRRSV free gilts were intranasally inoculated with a field isolate MN-30100 then assessed at various time points post infection. On day 120, pigs were re-exposed with MN-30100 PRRSV strain and subsequently were bled on days 0, 7, and 14 post re-exposure. Lymphocyte subpopulations, antigen specific proliferation, and IFN-gamma production were evaluated throughout the study. Circulating gammadelta lymphocytes in PRRSV exposed animals expanded between days 14 to 70 (d14-d70, p = 0.016); following antigen stimulation, gammadelta lymphocyte proliferated by day 14 (d0-d14, p = 0.001) continuing through day 60. gammadelta lymphocytes produced IFN-gamma by day 14 pi continuing through day 50 (d0-d50, p = 0.004). Following re-exposure both gammadelta+ and CD4+ lymphocytes increased in IFN-gamma production. These results are not fully conclusive on the role of gammadelta lymphocytes against PRRSV; the data indicate that gammadelta lymphocytes specifically respond to PRRSV.

  19. Quantification of Lymphocyte Dynamics

    NARCIS (Netherlands)

    Westera, L.

    2014-01-01

    The different lymphocyte populations of the immune system are maintained at fairly constant numbers throughout life. The importance of this lifelong maintenance is illustrated by clinical conditions of lymphopenia, such as human immunodeficiency virus infection, severe combined immune deficiency, or

  20. Nuclear proliferation

    International Nuclear Information System (INIS)

    Stencel, S.

    1978-01-01

    The terms and reactions to President Carter's nuclear policy, culminating in the 1978 Nuclear Non-Proliferation Act, are reviewed and analyzed. The new law increases restrictions on nuclear exports, encourages continued use of light water reactors in preference to plutonium-fueled reactors, and emphasizes technical solutions to proliferation problems. Critics of the law point out that it will hurt U.S. trade unfairly, that other countries do not have as many fuel options as the U.S. has, and that nuclear sales have as many political and economic as technical solutions. Compromise areas include new international safety guidelines, the possibility of an international nuclear fuel bank, and a willingness to consider each case on its merits. 21 references

  1. Cell titration assay for measuring blastogenesis of bovine lymphocytes.

    Science.gov (United States)

    Baldwin, C L; Antczak, D F; Winter, A J

    1985-08-01

    The blastogenic response of bovine peripheral blood lymphocytes to phytohemagglutinin (PHA) and to microbial antigens was measured using a lymphocyte titration assay. Culture conditions, including lymphocyte concentrations, incubation periods and medium formulation, were established which produced linear or nearly linear responses over a range of cell concentrations. These conditions were established by testing lymphocytes from unimmunized cattle and from heifers infected with Brucella abortus with PHA and a B. abortus extract. Four cell concentrations in 2-fold increments were selected for measuring responses to PHA (3.125 X 10(3) to 2.5 X 10(4) cells/well) and to antigens (5.0 X 10(4) to 4.0 X 10(5) cells/well). The strength of response varied among animals and also over time for individual animals, but the titration assay allowed exponential proliferation to be distinguished from decline, which may have been due to overcrowding of microtiter wells, exhaustion of nutrients or induction of regulatory events. This assay provided a more reliable and discriminating method of evaluating lymphocyte proliferation responses than that achieved by single point assays. The displacement of the titration curves could be used to estimate the relative frequency of lymphocytes responding to antigens or mitogens.

  2. The germinal center: a crucible for lymphocyte selection.

    Science.gov (United States)

    Kelsoe, G

    1996-06-01

    Antigen first activates T and B lymphocytes in the T-cell areas of secondary lymphoid tissues where cognate- and costimulus-dependent proliferation expands the population of reactive lymphocytes. Selected T- and B-cell progeny from this population migrate into B-cell zones to form germinal centers (GC), where intense proliferation, apoptosis, and V(D)J hypermutation takes place. It is now known that each of these processes occur in both compartments of GC lymphocytes and that the GC T-cell represents an unusual Thy-1- subset of alpha beta T-helper cells that may represent a terminally differentiated cell that is lost with the end of the GC reaction.

  3. Lymphocytic cholecystitis/cholangitis.

    Science.gov (United States)

    Jessurun, Jose

    2015-01-01

    To describe four cases of an uncommon type of acalculous cholecystitis/cholangitis characterized by increased intraepithelial lymphocytes within the biliary epithelium. Cases were prospectively compiled during regular surgical pathology sign-out. Clinical information was obtained from the electronic medical record and the gross appearance from the surgical pathology reports. Microscopic examination was performed with emphasis on the type, location, and distribution of the inflammatory pattern; presence of intraepithelial lymphocytes (>30 per 100 biliary cells); and presence of metaplasia and epithelial hyperplasia. Immunohistochemical stains for CD3, CD8, and IgG4 were performed in some cases. All patients were adults who had either biliary pain or obstructive symptoms. All gallbladders had a relatively normal gross appearance and did not contain gallstones or biliary sludge. Microscopic examination showed numerous intraepithelial lymphocytes in the biliary epithelium. The mucosa was frequently expanded by dense inflammatory cell infiltrates. The inflammatory process was more severe in the infundibulum and bile ducts than in the body of the gallbladder. The intraepithelial lymphocytes were CD3+, CD8+. IgG4+ plasma cells were absent. The term lymphocytic cholecystitis/cholangitis is proposed. The potential clinical implications and pathogenesis of this inflammatory pattern and the differential diagnosis with other forms of acalculous cholecystitis are discussed. Copyright© by the American Society for Clinical Pathology.

  4. Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: in vitro selection from unprimed rat T lymphocyte populations.

    Science.gov (United States)

    Schluesener, H J; Wekerle, H

    1985-11-01

    Autoimmune T lymphocyte lines have been established from unprimed normal rat lymph node cell populations. In a first, negative-selection round, spontaneously proliferating (SMLR) T cells were eliminated by a pulse of BUdR followed by short wave light irradiation. In a second, positive-selection round, the SMLR-depleted populations were confronted with MBP presented by syngeneic spleen adherent cells. Reactive T cells were propagated until stable, permanent T lines were established. All lines were exclusively specific for the selecting antigen, MBP, and were restricted in recognition by determinants of the own MHC. All lines expressed the differentiation marker W3/25, but not OX8. Line vLe, which was derived from Lewis (LEW) rat lymphocytes, and which recognized the encephalitogenic sequence 48-88 of MBP, was extremely efficient in mediating EAE to normal untreated LEW rats. Doses of 1 X 10(6) and greater transferred lethal EAE, whereas transient although definite disease was caused by a minimum of 1 X 10(4) cells. Rats recovering from disease were resistant against subsequent active induction of EAE. In contrast, BN rat-derived line vBN was completely incapable of transferring EAE to syngeneic rats. This lack of encephalitogenicity was a property of the T line, because vLe cells transferred severe EAE to (LEW X BN)F1 hybrid rats, whereas none of hybrid rats injected with vBN cells showed any sign of disease. The data provide strong evidence in favor of the presence of potentially autoaggressive T clones in the normal immune system, and they might suggest that the actual proportion of these clones within the natural T cell repertoire is genetically determined.

  5. 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

  6. Influence factors of human T lymphocyte co-stimulatory effect in vitro

    International Nuclear Information System (INIS)

    Zhou Jianhua; Su Liaoyuan; Tong Jian; Xue Lian

    2000-01-01

    Objective: Effects of CD3 McAb, CD28 McAb, PHA and low-dose γ-ray irradiation on T lymphocytes were investigated to explore factors of influencing T cell signals transduction. Method: Using CD3 McAb and CD28 McAb mimicking as the first and the second signals, and using PHA and low dose γ-rays irradiation as stimulatory factors in T cell activation, the influences of these factors and the two signals on human lymphocyte proliferation response were studied with 3 H-thymidine incorporation. Results: Lymphocyte proliferation response occurred when the two signals were treated co-stimulation or within certain intervals (within 40h). PHA and 10 cGy γ-rays irradiation can also activate lymphocytes to proliferate. However, each of the two signals alone did not activate lymphocytes to proliferate. Conclusion: CD3 McAb, CD28 McAb, PHA and low-dose γ-rays irradiation could stimulate T lymphocyte proliferation, which is an important aspect in cellular immune regulation

  7. Effect of oral proguanil on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    is increased by pyrimethamine and cycloguanil, reflecting blockage of endogenous TdR synthesis [3]. Proguanil (Paludrine) is increasingly being used for malaria prophylaxis. It is considered the most innocuous of the antimalarials currently employed. Since nothing is known about the effect of oral proguanil...

  8. Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats.

    Science.gov (United States)

    She, Yue; Wang, Nan; Chen, Chongxiao; Zhu, Yanzhu; Xia, Shiliang; Hu, Chongwei; Li, Yanfei

    2012-06-01

    The effects of Aluminum (Al) exposure on immune functions of cultured splenic T and B lymphocytes of rats were studied. The lymphocytes were isolated from spleen of healthy male Wistar rats weighing 110-120 g. The cultured cells in RPMI-1640 medium were exposed to 0 (control group), 0.035 (low-dose group), 0.07 (medial-dose group), and 0.14 (high-dose group) mg/mL Al(3+) as aluminum trichloride (AlCl(3)) in an incubator under 5% CO(2) at 37°C for 24 h. The T and B lymphocyte proliferation was measured with a tetrazolium dye colorimetric assay. The levels of interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α were determined by iodine [(125)I] IL-2, IL-6, and TNF-α radioimmunoassay kits, respectively. The proportions of CD3(+), CD4(+), and CD8(+) T lymphocytes were measured with a flow cytometer. The results showed that the T and B lymphocyte proliferation, the levels of IL-2, IL-6, TNF-α, the proportions of CD3(+) and CD4(+) T lymphocytes, and the ratio of CD4(+)/CD8(+) T lymphocytes were lowered by Al treatments, while the proportion of CD8(+) T lymphocytes was increased. These findings indicate that Al exposure can inhibit the immune functions of splenic T and B lymphocytes of rats in vitro.

  9. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  10. Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat

    International Nuclear Information System (INIS)

    Tanaka, S.; Sakai, A.

    1979-01-01

    The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulatng capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3 H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude

  11. Streptococcus pneumoniae cocultured with fibroblasts enhances both interferon production and cytotoxic activity by lymphocytes.

    OpenAIRE

    Weigent, D A; Baron, S; Stanton, G J

    1985-01-01

    Cell-mediated cytotoxicity against normal human fibroblasts was dependent on treatment of the fibroblasts with Streptococcus pneumoniae. Both spontaneous and interferon (IFN)-enhanced lymphocytes killed human foreskin (HFS) or skin muscle cells cocultured with S. pneumoniae five- to eightfold more than control nontreated cells. Based on Percoll gradient centrifugation, the cytotoxic effector cell migrated like a large granular lymphocyte. The human IFN produced from mixtures of HFS cells, lym...

  12. Renal carcinoma cell-derived exosomes induce human immortalized line of Jurkat T lymphocyte apoptosis in vitro.

    Science.gov (United States)

    Yang, Lin; Wu, Xiaohou; Wang, Dan; Luo, Chunli; Chen, Lixue

    2013-01-01

    Tumor-derived exosomes usually contain some molecules that can help immune evasion by tumors. This study is aimed at investigating the potential effect of exosomes from human kidney adenocarcinoma cells on a human immortalized line of Jurkat T lymphocytes in vitro. Exosomes were purified from human kidney adenocarcinoma ACHN cells by sequential centrifugations and ultrafiltrations, and characterized by transmission electron microscopy. The effects of exosomes on the proliferation, cytokine production and apoptosis of Jurkat T cells were determined using flow cytometry and enzyme-linked immunosorbent assay. The relative levels of pro- and anti-apoptotic molecules were determined by Western blotting. Exosomes were purified from ACHN cells and exhibited typical characteristics. Treatment with exosomes inhibited Jurkat T cell proliferation and induced Jurkat T cell apoptosis in a dose- and time-dependent manner. Treatment with exosomes reduced spontaneous interleukin-2 (IL-2), interferon-γ, IL-6 and IL-10 production by Jurkat T cells. Treatment with exosomes increased the relative levels of cleaved caspase-3, -8 and -9 as well as Bax, but reduced the levels of Bcl-2 in Jurkat T cells. The purified exosomes contained Fas ligand, and treatment with soluble Fas abrogated exosome-mediated Jurkat T cell apoptosis. Our data indicate that exosomes from kidney adenocarcinoma cells contain Fas ligand and trigger Jurkat T cell apoptosis, contributing to the immune evasion of tumors. Copyright © 2013 S. Karger AG, Basel.

  13. Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes

    International Nuclear Information System (INIS)

    Caporossi, D.; Sebastiani, G.; Nicoletti, B.; Masala, C.

    1990-01-01

    The authors conducted a study on the spontaneous and UV-A induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2-groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. (author). 14 refs.; 1 fig.; 3 tabs

  14. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

    Science.gov (United States)

    Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

    2011-03-25

    Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  15. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Science.gov (United States)

    2011-01-01

    Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

  16. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Directory of Open Access Journals (Sweden)

    Chang Shwu-Fen

    2011-03-01

    Full Text Available Abstract Background Arctium lappa (Niubang, a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC, isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2 and interferon-γ (IFN-γ production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  17. Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy.

    Science.gov (United States)

    Fujimura, Masato; Masuda, Kenichi; Hayashiya, Makio; Okayama, Taro

    2011-10-01

    Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (Pfood allergens may be involved in the pathogenesis of canine FA.

  18. D-ribose inhibits DNA repair synthesis in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Zunica, G.; Marini, M.; Brunelli, M.A.; Chiricolo, M.; Franceschi, C.

    1986-07-31

    D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks.

  19. Automated Scoring and Analysis of Micronucleated Human Lymphocytes.

    Science.gov (United States)

    Callisen, Hannes Heinrich

    Physical and chemical mutagens and carcinogens in our environment produce chromosome abberations in the circulating peripheral blood lymphocytes. The abberations, in turn, give rise to micronuclei when the lymphocytes proliferate in culture. In order to improve the micronucleus assay as a method for screening human populations for chromosome damage, I have (1) developed a high-resolution optical low-light-level micrometry expert system (HOLMES) to digitize and process microscope images of micronuclei in human peripheral blood lymphocytes, (2) defined a protocol of image processing techniques to objectively and uniquely identify and score micronuclei, and (3) analysed digital images of lymphocytes in order to study methods for (a) verifying the identification of suspect micronuclei, (b) classifying proliferating and non-proliferating lymphocytes, and (c) understanding the mechanisms of micronuclei formation and micronuclei fate during cell division. For the purpose of scoring micronuclei, HOLMES promises to (a) improve counting statistics since a greater number of cells can be scored without operator/microscopist fatigue, (b) provide for a more objective and consistent criterion for the identification of micronuclei than the human observer, and (c) yield quantitative information on nuclear and micronuclear characteristics useful in better understanding the micronucleus life cycle. My results on computer aided identification of micronuclei on microscope slides are gratifying. They demonstrate that automation of the micronucleus assay is feasible. Manual verification of HOLMES' results show correct extraction of micronuclei from the scene for 70% of the digitized images and correct identification of the micronuclei for 90% of the extracted objects. Moreover, quantitative analysis on digitized images of lymphocytes using HOLMES has revealed several exciting results: (a) micronuclear DNA content may be estimated from simple area measurements, (b) micronuclei seem to

  20. Effect of quercetin and 17-AAG on radiosensitivity of rat peripheral blood lymphocyte

    International Nuclear Information System (INIS)

    Chu Xuegang; Hong Chengjiao; Zhang Baoguo

    2012-01-01

    To investigate the effect of quercetin and 17-AAG on proliferation and on radiosensitivity of blood lymphocyte cells. CCK-8 assay is performed to evaluate the cytotoxicity of Quercetin on proliferation of blood lymphocyte cells. CCK-8 assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). CCK-8 results showed that the inhibition of Quercetin on the cells was the dose-dependent and time-dependent, and the results of assay showed the inhibition of 17-AAG on blood lymphocyte cells was the dose-dependent and time-dependent. The study showed that Quercetin and 17-AAG have no effect on the radiosensitivity of the blood lymphocyte cells. (authors)

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

    Science.gov (United States)

    2018-01-26

    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

  2. [Lymphocyte subpopulations in alopecia areata].

    Science.gov (United States)

    Calandria, L; Paciel, J; Bruno, J; Martini, M; Vignale, R; Civila, E

    1986-01-01

    Subsets of peripheral blood lymphocytes were studied in 19 patients with alopecia areata. The results shows: a decreased Tm/Tg ratio, decreased number of OKT4+ cells, increased OKT8+ cells, decreased OKT4+/OKT8+ cell ratio. Total lymphocytes, T cells, Tm cells, Tg cells, T DR+ cells and B lymphocytes were normal. The results are similar to those founded in autoimmune diseases and suggest the existence of an immunopathogenic mechanism in these disease.

  3. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  4. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  5. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes

    OpenAIRE

    Mello, Karina Faccio; Lunardelli, Adroaldo; Donadio, Márcio Vinícius Fagundes; Caberlon, Eduardo; Oliveira, Carmen Silvana Araújo de; Bastos, Carolina Maria Alves; Pires, Melissa Guerra Simões; Nunes, Fernanda Bordignon; Oliveira, Jarbas Rodrigues de

    2011-01-01

    INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulate...

  6. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  7. 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...... with various homing molecules and respond to tightly regulated navigational cues....

  8. Zinc intervention on macrophages and lymphocytes responce

    Energy Technology Data Exchange (ETDEWEB)

    Lastra, M.D.; Pastelin, R.; Camacho, A.; Monroy, B.; Aguilar, A.E. [Lab. de Investigacion en Immunologia, Univ. Nacional Autonoma de Mexico (Mexico)

    2001-07-01

    Normal zinc levels are essential for the development and maintenance of immune functions; Zn deficiency is detrimental to the embryo and offspring of experimental animals, especially concerning immune development. It is known that Zn supplementation improves immune responses. To further explore the relation between Zn administration and the metal in vitro effects, we studied zinc (500 mg/l) supplementation impact on lymphocytes and macrophages and zinc in vitro effects, in BALB/c mice supplemented from gestation to lactation. Results show a significant increase in proliferation (assessed by {sup 3}H incorporation) in lymphocytes exposed to Zn (0.1 mM) in vitro, in 3-wk-old mice; this effect is annulled when the supplementation period is lengthened, indicating saturation of the mechanisms involved in zinc induced stimulation. Macrophages functional capacity assessed by erythrophagocytosis was also improved by Zn supplementation and furthermore by the in vitro exposure to the metal, in mice 3 wk old, this was also depressed by Zn accumulation due to the supplementation period extension (9 weeks). Results show an improvement in the immune parameters analysed due to zinc supplementation and to zinc in vitro exposure. Results also suggest the accumulation of zinc as a result of prolonged supplementation periods, suppresses the cells response to zinc in vitro. (orig.)

  9. Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

    DEFF Research Database (Denmark)

    Kelsen, Jesper; Larsen, Marianne; Sørensen, Jens Christian H.

    2010-01-01

    We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats...

  10. Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

    DEFF Research Database (Denmark)

    Kelsen, Jesper; Larsen, Marianne; Sørensen, Jens Christian H.

    2010-01-01

    We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats ...

  11. Radiosensitivity of lymphocytes in vitro

    International Nuclear Information System (INIS)

    Albrecht, S.

    1979-01-01

    The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60 Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3 H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

  12. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    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.

  13. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes.

    Science.gov (United States)

    Pongsavee, Malinee

    2009-10-30

    Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  14. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    Directory of Open Access Journals (Sweden)

    Pongsavee Malinee

    2009-10-01

    Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  15. Ouabain exacerbates activation-induced cell death in human peripheral blood lymphocytes

    OpenAIRE

    Esteves Mabel B.; Marques-Santos Luis F.; Affonso-Mitidieri Ottília R.; Rumjanek Vivian M.

    2005-01-01

    Lymphocytes activated by mitogenic lectins display changes in transmembrane potential, an elevation in the cytoplasmic Ca2+ concentrations, proliferation and/or activation induced cell death. Low concentrations of ouabain (an inhibitor of Na+,K+-ATPase) suppress mitogen-induced proliferation and increases cell death. To understand the mechanisms involved, a number of parameters were analyzed using fluorescent probes and flow cytometry. The addition of 100nM ouabain to cultures of peripheral b...

  16. VASCULAR PROLIFERATION AS AN UNUSUAL CAUSE OF HEMORRHAGIC DIATHESIS IN MYELOFIBROSIS

    NARCIS (Netherlands)

    ALBEDA, FW; VANDERMEER, J; VELLENGA, E

    One year after splenectomy, a patient with myelofibrosis developed spontaneously large hematomas that were not due to coagulation abnormalities or functionally defective platelets. At autopsy, the liver, muscle, and skin showed extramedullary hematopoiesis associated with capillary proliferation and

  17. The threat of proliferation

    International Nuclear Information System (INIS)

    Palme, Olof.

    1986-01-01

    The paper on the threat of proliferation, is a keynote speech delivered to the Colloquium on Nuclear War, Nuclear Proliferation and their Consequences, Geneva, 1985. Topics discussed in the address include: nuclear weapons, nuclear war, terrorists, Non-Proliferation Treaty, nuclear disarmament, and leadership in world affairs. (UK)

  18. Effects of norepinephrine on immune functions of cultured splenic lymphocytes exposed to aluminum trichloride.

    Science.gov (United States)

    Zhang, Ji-Hong; Hu, Chong-Wei; Zhu, Yan-Zhu; Liu, Shi-Min; Bai, Chong-Sheng; Han, Yan-Fei; Xia, Shi-Liang; Li, Yan-Fei

    2013-08-01

    The aim of this study was to investigate the effect of norepinephrine (NE) on spleen lymphocytes exposed to aluminum trichloride (AlCl3). In this experiment, lymphocytes were isolated from spleens of healthy Wistar rats weighing about 130 g and cultured with RPMI-1640 medium containing the final concentration of 0.552 mmol/L AlCl3. NE was added to the cultured cells at the final concentrations of 0 (control group), 0.1 (low-dose group), 1 (mid-dose group), and 10 (high-dose group) nmol/L. No addition of both AlCl3 and NE serviced as blank (BG). The T lymphocyte proliferation; the contents of IL-2, TNF-α, and T lymphocyte subsets; immunoglobulin G (IgG) and intracellular cyclic adenosine monophosphate (cAMP) concentrations; and β2-adrenergic receptor (β2-AR) density were measured at the end of the culture. The result showed that NE decreased T lymphocyte proliferation and the contents of IL-2, TNF-α, and T lymphocyte subsets whereas increased the concentrations of IgG and intracellular cAMP and β2-AR density of the lymphocyte exposed to AlCl3. AlCl3 exposure without adding NE showed the similar impacts on these measures compared with BG. The results suggested that NE aggravated AlCl3 immunotoxicity on the lymphocytes and disordered the immune functions of the lymphocyte through the β2-AR-cAMP signal pathway.

  19. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  20. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  1. Fissile material proliferation risk

    International Nuclear Information System (INIS)

    Dreicer, J.S.; Rutherford, D.A.

    1996-01-01

    The proliferation risk of a facility depends on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. To effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of nuclear related sites and facilities in different countries and still ensure a global decrease in proliferation risk for fissile material (plutonium and highly enriched uranium)

  2. [Immune regulatory effect of human bone marrow mesenchymal stem cells on T lymphocyte].

    Science.gov (United States)

    Lu, Xiao-Xi; Liu, Ting; Meng, Wen-Tong; Zhu, Huan-Ling; Xi, Ya-Ming; Liu, Yong-Mei

    2005-08-01

    To investigate the immune regulatory effects of human bone marrow mesenchymal stem cells on alloantigen T lymphocyte in vitro, human MSCs were isolated and expanded from bone marrow cells, and identified with cell morphology, and the phenotypes were assessed by immunohistochemistry and flow cytometry. As the stimulation factor of T lymphocytes proliferation, either PHA or dendritic cells isolated from cord blood were cocultured with CD2(+) T lymphocytes from peripheral blood mononuclear cells by magnetic beads with or without MSC in 96-well plats for seven days. T cell proliferation was assessed by [(3)H]-thymidine incorporation using a liquid scintillation counter. T cell subsets, Th1, Th2, Tc1 and Tc2 were analyzed by flow cytometry after co-culture of CD2(+) T cells with MSCs for 10 days. The results showed that a significant decrease of CD2(+) T cell proliferation was evident when MSC were added back to T cells stimulated by DC or PHA, and an increase of Th2 and Tc2 subsets were observed after co-culture of MSC with T lymphocytes. It is suggested that allogeneic MSC can suppress T cell proliferation in vitro and the cause of that was partly depend on interaction of cells and the alteration of T cell subsets.

  3. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  4. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  5. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  6. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  7. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  8. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

    Science.gov (United States)

    Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2009-06-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.

  9. Effects of Corticosterone on Immune Functions of Cultured Rat Splenic Lymphocytes Exposed to Aluminum Trichloride.

    Science.gov (United States)

    Yang, Xu; Xu, Feibo; Zhuang, Cuicui; Bai, Chongsheng; Huang, Wanyue; Song, Miao; Han, Yanfei; Li, Yanfei

    2016-10-01

    Aluminum (Al) exposure is toxic to immune system. Studies have implicated that glucocorticoids (GCs) exert the dual regulation effect on the immune function depending on the concentration. However, it is unknown whether a dual effect of GCs exists in the AlCl3-treated lymphocytes. Corticosterone (Cort) is one kind of GCs. To investigate the effect of different concentration Cort on AlCl3-treated lymphocytes, rat splenic lymphocyte was isolated and cultured with 0.55 mmol/L AlCl3, simultaneously administrated Cort at final concentration of 0 (control group, CG), 10(-8) (low-level group, LG), and 10(-6) (high-level group, HG) mol/L, respectively. Another group without AlCl3 and Cort served as the blank group (BG). We found that low concentration Cort increased the T and B lymphocyte proliferation rate, proportions of CD4(+) T lymphocyte subset, IgG, IL-2, and TNF-α contents, whereas high concentration Cort decreased those in AlCl3-treated lymphocytes. In conclusion, the results of this study indicated that low concentration Cort relieves the immunotoxicity of AlCl3 on the splenic lymphocytes, whereas high concentration Cort aggravates it.

  10. France and nuclear proliferation

    International Nuclear Information System (INIS)

    Barrillot, B.

    2001-05-01

    The Observatory of French nuclear weapons looks forwards to the elimination of nuclear weapons in conformity with the aims of the nuclear non-proliferation Treaty. This file tackles the breakdown of disarmament, the missile-launching nuclear submarines ( new generation) program counter to non-proliferation, nuclear submarines, security and health, nuclear submarines and the environment, the program itself and the requirements of the non proliferation treaty. (N.C.)

  11. Globalization and Proliferation

    Science.gov (United States)

    2005-08-01

    growing with each other? Is the process of globalization as it makes technology , education, etc., available to more and more coun- tries—and even...So to conclude, I ask, does globalization make the world go to hell because of rampant proliferation of technology , falling into the 23. And their...CIM D0012837.A1/Final August 2005 Globalization and Proliferation A presentation to a Workshop on Proliferation Networks at the Naval

  12. Proliferation: myth or reality?

    International Nuclear Information System (INIS)

    2005-01-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  13. Selective loss of T cell functions in different stages of HIV infection. Early loss of anti-CD3-induced T cell proliferation followed by decreased anti-CD3-induced cytotoxic T lymphocyte generation in AIDS-related complex and AIDS

    NARCIS (Netherlands)

    Gruters, R. A.; Terpstra, F. G.; de Jong, R.; van Noesel, C. J.; van Lier, R. A.; Miedema, F.

    1990-01-01

    To investigate the effects of persistant human immunodeficiency virus (HIV) infection on T cell reactivity, functional properties of peripheral blood T cells from HIV-seropositive homosexual men in various stages of infection were studied. T cell activation via CD3 resulting in proliferation and

  14. Spontaneous pregnancy during ulipristal acetate treatment of giant uterine leiomyoma.

    Science.gov (United States)

    Hrgovic, Z; Habek, D; Cerkez Habek, J; Hrgovic, I; Jerkovic Gulin, S; Gulin, D

    2018-02-01

    Ulipristal acetate, a progesterone receptor modulator, pharmacologically inhibits endometrial proliferation and thereby prevents pregnancy. It is primarily used as emergency contraception, but also for the treatment of fibroids in women of reproductive age. There have been no published cases of pregnancy, while on therapy with ulipristal acetate. In this article, we present a case report of spontaneous pregnancy during ulipristal acetate therapy. To our knowledge, this is the first patient with spontaneous conception, while on ulipristal acetate treatment. There were no drug-related complications, and the pregnancy resulted in the delivery of a healthy baby. © 2017 John Wiley & Sons Ltd.

  15. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  16. [Lymphocyte stimulation test, a possible alternative for verifying chloroacetophenone sensitization].

    Science.gov (United States)

    Brand, C U; Schmidli, J; Ballmer-Weber, B; Hunziker, T

    1995-10-01

    We report on a case of pronounced sensitization to chloroacetophenone tear gas that developed after repeated occupational skin exposure in a 57-year-old police officer. Mainly in the presence of moisture and occlusion, cutaneous application of chloroacetophenone leads to severe irritant, and often also allergic, skin reactions. In patch testing the demonstration of allergic contact dermatitis in response to chloroacetophenone is hampered by the irritative potential of this substance even at low concentrations. This diagnostic bias can be overcome by the lymphocyte proliferation assay.

  17. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  18. Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation

    OpenAIRE

    Vander Heiden, Matthew G.; Lunt, Sophia Yunkyungkwon

    2011-01-01

    Warburg's observation that cancer cells exhibit a high rate of glycolysis even in the presence of oxygen (aerobic glycolysis) sparked debate over the role of glycolysis in normal and cancer cells. Although it has been established that defects in mitochondrial respiration are not the cause of cancer or aerobic glycolysis, the advantages of enhanced glycolysis in cancer remain controversial. Many cells ranging from microbes to lymphocytes use aerobic glycolysis during rapid proliferation, which...

  19. Radiation induced chromosomal instability in lymphocytes of cancer patients

    International Nuclear Information System (INIS)

    Sudo, H.; Sagara, M.; Ban, S.; Noda, S.; Iwakawa, M.; Harada, Y.; Imai, T.; Cologne, J.B.

    2003-01-01

    Full text: Cytokinesis-blocked micronucleus (CBMN) assay has been extensively used to evaluate the radiation sensitivity of human individuals. Using the CBMN assay, Scott et al (1998, 1999) demonstrated that a fraction of radiosensitive individuals in breast cancer case population was larger than in normal individual population. However, Vral et al were very skeptical about the Scott et al's findings (2002). Under the approval from the ethical committee of NIRS, peripheral blood was obtained from 46 normal healthy females, 131 breast cancer patients, 32 cervical cancer patients and 7 female head and neck cancer patients. Radiosensitivity of T-lymphocytes was assessed by using a CBMN assay. The frequencies of MN per binucleated cell in healthy donors were 0.031(±0.010) and 0.151(±0.066) for cells treated before and after X-ray-irradiation (2Gy), respectively. Spontaneous MN frequencies in cancer patients were significantly higher than healthy donors (p < 0.001). Radiation sensitivities of breast- and head and neck-cancer patients were significantly higher than normal individuals (p < 0.001). Cervical cancer patients were more resistant to irradiation than healthy donors, though the number of cases for statistical analysis was small. (p < 0.001). We are considering that the HPV infection affected the radiosensitivity of cervical cancer cases. Because it is widely believed that one key mechanism which leads to spontaneous micronucleus formation involves an imbalance of chromosomal segregation and a chromosomal instability in patients' lymphocytes might be greater than that in normal individuals' lymphocytes. Recently, Kuschel et al (2002) demonstrated that ratios in two SNPs on XRCC3 were significantly different between cancer patients and healthy females. Then, we can suppose that the radiation-related genes with low penetrance may be involved in tumorigenesis of mammary- and head and neck-cells, and also, in patients' radiation susceptibility

  20. Director's series on proliferation

    International Nuclear Information System (INIS)

    Bailey, K.C.; Price, M.E.

    1995-01-01

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author's. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia's Nuclear Legacy

  1. Proliferation Networks and Financing

    International Nuclear Information System (INIS)

    Gruselle, Bruno

    2007-01-01

    The objective of this study is to propose practical solutions aimed at completing and strengthening the existing arrangement for the control of nuclear proliferation through a control of financial as well as material or immaterial flows. In a first part, the author proposes a systemic analysis of networks of suppliers and demanders. He notably evokes the Khan's network and the Iraqi acquisition network during the 1993-2001 period. He also proposes a modelling of proliferation networks (supplier networks and acquisition networks) and of their interactions. In a second part, the author examines possible means and policies aimed at neutralising proliferation networks: organisation, adaptation and improvement of intelligence tools in front of proliferation networks, and means, limitations and perspectives of network neutralisation. He also briefly addresses the possibility of military action to contain proliferation flows

  2. Predictive radiosensitivity tests in human lymphocytes

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Vallerga, Maria B.; Taja, Maria R.; Sardi, M.; Busto, E.; Mairal, L.; Roth, B.; Menendez, P.; Bonomi, M.

    2004-01-01

    comparing expected MN frequencies (calibration curve from healthy donors) with values observed after in vitro irradiation. One over-reactor and patients that did not develop late effects were also evaluated through comet assay. Blood samples were in vitro irradiated with 2 Gy and DNA repair capacity was evaluated for initial damage and after different periods of incubation at 37 C degree. DNA damage and repair capacity were quantified by the Olive tail moment. MN assay resulted suitable for the evaluation of individual cytogenetic response to radiotherapy in body areas having a large blood volume and flow or including bone marrow, suggesting that lymphocyte remixing contributes to an homogenisation of the total absorbed dose. In the prospective evaluation, the MN assay correlated with the clinical late toxicity, over 2 Gy equivalent whole-body dose. Therefore, the predictive potential of MN assay results limited by the requirement to accumulate 2 Gy equivalent whole-body dose to find a substantial difference in the DNA repair capacity, measured through k parameter. In the retrospective evaluations both, spontaneous and in vitro radiation-induced micronucleus frequencies were significantly increased, compared with the expected values from the calibration curve, in patients who had developed late tissue reactions. The assessment of the repair kinetics in the lymphocytes of the patient with severe late effects supports the comet assay as a useful indicator for individual radiosensitivity. As a conclusion, MN and comet tests could be suitable predictive assays to evaluate individual radiosensitivity in vitro, contributing with the detection of patients that would develop late adverse reactions. This knowledge would provide further applications on radiation protection field. (author)

  3. Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    Barsegian, Vahe; Moeckel, Daniel; Mueller, Stefan P.; Bockisch, Andreas; Horn, Peter A.; Lindemann, Monika

    2017-01-01

    Therapy with the alpha-emitter radium-223 chloride ( 223 Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if 223 Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving 223 Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after 223 Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

  4. Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barsegian, Vahe; Moeckel, Daniel [Helios Kliniken, Institute of Nuclear Medicine, Schwerin (Germany); Mueller, Stefan P.; Bockisch, Andreas [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Horn, Peter A.; Lindemann, Monika [University Hospital Essen, Institute for Transfusion Medicine, Essen (Germany)

    2017-02-15

    Therapy with the alpha-emitter radium-223 chloride ({sup 223}Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if {sup 223}Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving {sup 223}Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after {sup 223}Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

  5. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  6. Radiosensitivity of lymphocytes among Filipinos: final report

    International Nuclear Information System (INIS)

    Medina, F.I.S.; Gregorio, J.S.; Aguilar, C.P.; Poblete, E.E.

    1996-01-01

    This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

  7. A microculture technique for rat lymphocyte transformation.

    Science.gov (United States)

    Lindsay, V J; Allardyce, R A

    1979-01-01

    We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

  8. The significance of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in vestibular neuritis.

    Science.gov (United States)

    Chung, Jae Ho; Lim, Jonghyun; Jeong, Jin Hyeok; Kim, Kyung Rae; Park, Chul Won; Lee, Seung Hwan

    2015-07-01

    To investigate the significance of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in vestibular neuritis. Retrospective, case-control study. The study subjects were patients who received treatment for vestibular neuritis between January 2009 and December 2013, and a control group composed of 70 age- and sex-matched healthy subjects who received laboratory testing as part of a routine health checkup. The subjects underwent a complete blood cell count and counts of the various cell subtypes to compare NLR and PLR in the vestibular neuritis patients and controls. The associations between laboratory test results and values of the vestibular function test and clinical information were examined. In addition, a subgroup analysis according to the duration of spontaneous nystagmus was performed. The mean NLR and PLR values of the patient group were significantly higher than those of the control group. Although caloric test outcomes and hospitalization period were not significantly correlated with blood profiles, the duration of dizziness needing antivertiginous drugs was positively correlated with NLR and PLR (P = .021, P = .020, respectively). In addition, NLR was negatively correlated with the length of time between symptom start and blood sampling (P = .005). The NLR and PLR value of patients with nystagmus for more than 5 days were significantly higher than those of patients whose nystagmus ceased within 5 days. This is the first report to evaluate the significance of NLR and PLR in vestibular neuritis. NLR and PLR should be taken into consideration as simple and reliable parameters for predicting the cause and severity of the disease. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Non-proliferation

    International Nuclear Information System (INIS)

    Manley, I.T.

    1981-01-01

    Proliferation is a problem that can only be solved when the political problems which lead countries to contemplate, the possession of nuclear weapons are solved; in the meantime it can only be managed. Non-proliferation policy has to deal both with the political and the technical aspects of proliferation. It must seek to buy time by addressing the reasons why nations feel the political need to construct nuclear weapons, as well as delaying the moment when such nations feel capable of doing so. The subject is examined and proposals made. (author)

  10. Getting serious about proliferation

    International Nuclear Information System (INIS)

    Leventhal, P.

    1984-01-01

    The US needs to give a higher priority to nuclear non-proliferation, but Reagan's policies assume that proliferation is inevitable and that it is more important to be a reliable supplier than to cause trade frictions by trading only with those nations which sign the non-proliferation treaty (NPT). This undercuts US leadership and the intent of the agreement. Several bills now before Congress could help to restore US leadership by tightening export restrictions and the use of plutonium from the US

  11. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  12. The uptake kinetics and immunotoxic effects of microcystin-LR in human and chicken peripheral blood lymphocytes in vitro

    International Nuclear Information System (INIS)

    Lankoff, Anna; Carmichael, Wayne W.; Grasman, Keith A.; Yuan, Moucun

    2004-01-01

    Microcystin-LR is a cyanobacterial heptapeptide that presents acute and chronic hazards to animal and human health. We investigated the influence of this toxin on human and chicken immune system modulation in vitro. Peripheral blood lymphocytes were treated with microcystin-LR at environmentally relevant doses of 1, 10 and 25 μg/ml for 12, 24, 48, 72 h (for proliferation assay cells were treated for 72 h). T-cell and B-cell proliferation as well as apoptosis and necrosis were determined in human and chicken samples. IL-2 and IL-6 production by human lymphocytes also was measured. In addition, uptake kinetics of microcystin-LR into human and chicken peripheral blood lymphocytes were calculated by Liquid Chromatography (LS) /Mass Spectrometry (MS) analysis. At the highest dose microcystin-LR decreased T-cell proliferation and all doses of microcystin-LR inhibited B-cell proliferation. The frequency of apoptotic and necrotic cells increased in a dose and time-dependent manner. Human lymphocytes responded to stimulation with microcystin-LR by increased production of IL-6 and decreased production of IL-2. Human lymphocytes were able to uptake from 0.014 to 1.663 μg/ml and chicken lymphocytes from 0.035 to 1.733 μg/ml of the microcystin-LR added to the cultures, depending on the treatment time and dose. In conclusion, microcystin-LR acted as an immunomodulator in cytokine production and down-regulated lymphocyte functions by induction of apoptosis and necrosis. However, further studies dealing with the influence of microcystin-LR on expression cytokine genes and transcription factors are necessary to confirm these hypotheses

  13. Cruise Missile Proliferation

    National Research Council Canada - National Science Library

    Feickert, Andrew

    2005-01-01

    About 75 countries currently possess cruise missiles.1 Many experts predict that anti- ship and land attack cruise missile proliferation will increase in terms of both scope and technological sophistication...

  14. Countering Chinese Proliferation Activity

    National Research Council Canada - National Science Library

    Tomchik, Stephen J

    1994-01-01

    Control of the proliferation of nuclear technology (including fissile material), chemical and biological weapons and their precursors, and ballistic missile delivery systems continues to be a priority for the United States Government...

  15. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    OpenAIRE

    Pongsavee Malinee

    2009-01-01

    Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0...

  16. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  17. Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

    Directory of Open Access Journals (Sweden)

    Jorge Escobar

    2010-01-01

    Full Text Available Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance.

  18. Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

    Science.gov (United States)

    Escobar, Jorge; Varela-Nallar, Lorena; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Valdés, Daniel; Aspee, Alexis; Espinosa, Victoria; Rozas, Carlos; Montoya, Margarita; Mandiola, Cristian; Rodríguez, Felipe E.; Acuña-Castillo, Claudio; Escobar, Alejandro; Fernández, Ricardo; Diaz, Hernán; Sandoval, Mario; Imarai, Mónica; Rios, Miguel

    2010-01-01

    Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance. PMID:21253489

  19. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.

    Science.gov (United States)

    Tokoyoda, Koji; Zehentmeier, Sandra; Hegazy, Ahmed N; Albrecht, Inka; Grün, Joachim R; Löhning, Max; Radbruch, Andreas

    2009-05-01

    CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.

  20. Spontaneous aortic dissecting hematoma in two dogs.

    Science.gov (United States)

    Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William

    2005-09-01

    This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

  1. Impairment of lymphocyte function following yttrium-90 DOTATOC therapy.

    Science.gov (United States)

    Barsegian, Vahé; Hueben, Christian; Mueller, Stefan P; Poeppel, Thorsten D; Horn, Peter A; Bockisch, Andreas; Lindemann, Monika

    2015-06-01

    The radiolabeled somatostatin analogue, yttrium-90 DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC), is currently applied to treat advanced somatostatin receptor-positive tumors, e.g., neuroendocrine tumors of the pancreas, lung or gut. However, effects of this treatment on antimicrobial immune responses are not yet defined. In 20 patients treated with DOTATOC, cellular in vitro immune function was determined. Their antimicrobial lymphocyte responses were assessed by lymphocyte transformation test and enzyme-linked immunospot-measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10)-prior to therapy, at day 1, day 7 and day 90 post-therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were non-significantly suppressed at day 1 and significantly (p 90. In contrast, at day 1 interleukin-10 production was significantly (p < 0.05) increased. Taken together, we observed a decrease in pro-inflammatory immune responses after DOTATOC therapy. Patients with versus without bone metastases displayed significantly (p < 0.05) lower cellular immune responses toward several microbial antigens. Progressive disease and higher tumor burden could also be defined as factors associated with impaired immune function. Spearman correlation analysis indicated that cellular in vitro immunity was positively correlated with kidney function; better kidney function led to stronger immune responses. In conclusion, DOTATOC therapy caused a decrease in in vitro immune responses against microorganisms. The clinical impact needs to be evaluated in further studies.

  2. Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

    1981-01-01

    Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

  3. Nodular lymphocyte predominant Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Siddiqui, Neelam; Al-Diab, Abdulrahman I.

    2005-01-01

    To describe the clinicopathological features, treatment, treatment outcome and sequelae of patients with nodular lymphocyte, predominant Hodgkin's lymphoma (NLPHL) in Saudi population. This is a retrospective review of 29 patients with lymphocyte predominant Hodgkin's lymphoma treated at two major hospitals (King Khalid University Hospital and Security Forces Hospital) in Riyadh, Kingdom of Saudi Arabia from 1985 to 2000. Histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections and immunochemistry. Details of clinical presentation, stage, treatment and results of treatment were analyzed. On pathological reappraisal of the 29 cases, 3 patients had nodular sclerosis Hodgkin's lymphoma and 4 patients were reclassified as lymphocyte rich classical Hodgkin's lymphoma. Twenty-two patients were identified to have nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). These patients comprised of 18 mails and 4 female patients with a median age at presentation of 25 years. Nineteen (86%) patients had an early stage (Ann Arbor stage I and II) disease, 2 had stage III and one patient had stage IV. The majority of patients presented with peripheral lymphadenopathy and long duration of symptoms. For 16 patients, details of treatment and follow-up were available. All of these achieved a complete response to initial treatment. Four patients relapsed following the primary therapy. Our results are consistent with the previous series reported from Western countries and confirmed that the patients with NLPHL have characteristic clinical and pathological profile that distinguish it from other types of Hodgkin's lymphoma. The disease tends to run an unusual course and although most patients achieve an excellent response to therapy there is a tendency to replace. treatment remains controversial; however, recent understanding of the molecular pathogenesis of NLPHL could lead to modification of current therapeutic approach to this disease. (author)

  4. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  5. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  6. Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis.

    Science.gov (United States)

    Duarte, R; Kindlelán, J M; Carracedo, J; Sánchez-Guijo, P; Ramírez, R

    1997-01-01

    Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that resembles that of superantigens from alpha/beta T cells. After culture in vitro with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T lymphocytes from ACF-TBC patients occurs in a range similar to that observed in healthy subjects. Following activation, H37Ra-stimulated gamma/delta T lymphocytes from healthy subjects did proliferate in the presence of exogenous recombinant human interleukin 2. However, under the same conditions, gamma/delta T lymphocytes from ACF-TBC patients not only did not proliferate but died by apoptosis. These results suggest that in gamma/delta T lymphocytes from patients with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads to apoptotic cell death.

  7. Propiece IL-1α facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-κB and SP1.

    Science.gov (United States)

    Zhang, Yinsheng; Yu, Xiao; Lin, Dandan; Lei, Lei; Hu, Bo; Cao, Fengzhang; Mei, Yu; Wu, Depei; Liu, Haiyan

    2017-02-28

    Interleukin 1α (IL-1α) is a pro-inflammatory cytokine that possesses multiple immune-regulatory functions. It is mainly expressed as the cell-associated form and not actively secreted in healthy tissues. The intracellular IL-1α has been shown to be a chromatin-associated cytokine and can affect transcription. There are spontaneous expressions of IL-1α in acute lymphocytic leukemia (ALL) blasts. However, the role of nuclear-localized IL-1α in ALL is not clear. Here we showed that overexpression of the nuclear form of IL-1α (propiece IL-1α) could promote proliferation and reduce apoptosis of T-ALL cells. It also increased the ALL cells' resistance to low serum concentration and cisplatin treatment. In vivo growth of the T-ALL cells overexpressing the propiece IL-1α were also enhanced compared to the control cells. Microarray analysis revealed many changes in gene expressions related to cell growth and stress, including a group of metallothionein genes. Moreover, the expressions of transcription factors, NFκB and specific protein 1 (SP1), were up-regulated by propiece IL-1α. Propiece IL-1α could bind to the promoter of SP1 and a binding sequence logo was identified. Therefore, nuclear expression of propiece IL-1α can facilitate the growth of T-ALL cells possibly through the activation of NFκB and SP1.

  8. Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model

    NARCIS (Netherlands)

    Lascano, Valeria; Guadagnoli, Marco; Schot, Jan G.; Luijks, Dieuwertje M.; Guikema, Jeroen E. J.; Cameron, Katherine; Hahne, Michael; Pals, Steven; Slinger, Erik; Kipps, Thomas J.; van Oers, Marinus H. J.; Eldering, Eric; Medema, Jan Paul; Kater, Arnon P.

    2013-01-01

    Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in

  9. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  10. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  11. Effect of regular circus physical exercises on lymphocytes in overweight children.

    Directory of Open Access Journals (Sweden)

    Cesar Miguel Momesso dos Santos

    Full Text Available Obesity associated with a sedentary lifestyle can lead to changes in the immune system balance resulting in the development of inflammatory diseases. The aim of this study was to compare lymphocyte activation mechanisms between overweight children practicing regular circus physical exercises with non-exercised children. The study comprised 60 pubescent children randomly divided into 4 groups: Overweight Children (OWC (10.67 ± 0.22 years old, Overweight Exercised Children (OWE (10.00 ± 0.41 years old, Eutrophic Children (EC (11.00 ± 0.29 years old and Eutrophic Exercised Children (EE (10.60 ± 0.29 years old. OWE and EE groups practiced circus activities twice a week, for 4.3 ± 0.5 and 4.4 ± 0.5 months, respectively. Percentage of T regulatory cells (Treg and the expression of CD95 and CD25 in CD4+ lymphocytes were evaluated by flow cytometry. Lymphocyte proliferation capacity was measured by [14C]-thymidine incorporation and mRNA expression of IL-35, TGF-beta, IL-2 and IL-10 by real-time PCR. Lymphocyte proliferation was higher in OWC and OWE groups compared with the EC (3509 ± 887; 2694 ± 560, and 1768 ± 208 cpm, respectively and EE (2313 ± 111 cpm groups. CD95 expression on lymphocytes was augmented in the EC (953.9 ± 101.2 and EE groups (736.7 ± 194.6 compared with the OWC (522.1 ± 125.2 and OWE groups (551.6 ± 144.5. CTLA-4 expression was also lower in the OWC and OWE groups compared with the EC and EE groups. Percentage of Treg, IL-35, and IL-10 mRNA expression were lower in the OWC and OWE groups compared with the EC and EE groups. In conclusion, overweight children present altered immune system balance characterized by elevated lymphocyte proliferation due to a decrease in T regulatory cell percentage. These effects were partially reverted by moderate physical exercise, as demonstrated by decreased lymphocyte proliferation.

  12. Nuclear non-proliferation

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    DOE's nuclear non-proliferation responsibilities are defined by the provisions of the Atomic Energy Act of 1954, as amended, and of the Nuclear Non-Proliferation Act of 1978 (NNPA). The Department's major responsibilities in this area are to: (1) provide technical assistance to the Department of State in negotiating agreements for civil cooperation in the peaceful uses of nuclear energy with other countries and international organizations; (2) join with other agencies to reach executive branch judgments with respect to the issuance of export licenses by the Nuclear Regulatory Commission; (3) be responsible for processing subsequent arrangements with other agencies as required by the Nuclear Non-Proliferation Act; (4) control the distribution of special nuclear materials, components, equipment, and nuclear technology exports; (5) participate in bilateral and multilateral cooperation with foreign governments and organizations to promote the peaceful uses of nuclear energy; and (6) act as a primary technical resource with respect to US participation in the International Atomic Energy Agency

  13. Dynamics of nuclear proliferation

    International Nuclear Information System (INIS)

    Meyer, S.M.

    1984-01-01

    This book looks beyond policy disputes to make a systematic examination of the assumptions and contending hypotheses that constitute contemporary thinking on nuclear proliferation. Rather than determine who is right or wrong, the intent is to develop a better picture by using the various schools of thought as analytic windows. A better understanding of how the process operates should offer better guidance for predicting future nuclear proliferation and, ultimately, for controlling it. Separate chapters deal with the contending views, the technological and motivational bases of nuclear proliferation, the presence of a technological imperative, testing the motivational hypothesis, the dynamics of the process, and forecasting. Four appendices present historical decisions, the technical model, cost-estimating procedures, and procedures for estimating nuclear propensities. 288 references, 17 figures, 26 tables

  14. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  15. GADD45α is involved in the apoptosis of lymphocytes induced by riboflavin and ultraviolet light.

    Science.gov (United States)

    Yang, Peng; Wen, Huiqin; Zhong, Tao; Hu, Hailiang; Zhu, Bangqiang; Xia, Kang; Xu, Mo; Bian, Maohong

    2017-03-01

    Riboflavin plus ultraviolet (UV) pathogen reduction technology (RF-PRT) is an effective method for inactivating the residual white blood cells (WBCs) in blood components. The RF-PRT system for platelets is known to activate many signaling pathways, including p38 and NF-κB. Nevertheless, proteomic studies in WBCs after riboflavin plus UV treatment requires further analysis. ABO/D-matched lymphocytes were pooled, split, and treated with RF-PRT or UV light or left untreated. After treatment, cell apoptosis was measured. In addition, cell proliferation and the cycle distribution were evaluated upon stimulation with phytohemagglutinin. The changes in the protein expression levels of growth arrest and DNA damage-inducible (GADD)45α, p38, and c-Jun N-terminal kinase (JNK) were determined by Western blotting. The effect of GADD45α, p38, and JNK on apoptosis was assessed. RF-PRT significantly inhibited proliferation and induced G1 arrest in lymphocytes. Furthermore, the percentage of apoptotic cells was increased in RF-PRT-treated lymphocytes compared to UV-treated cells or untreated cells, associated with the up regulation of GADD45α expression. Consistent with these observations, the inhibition of GADD45α expression partially counteracted the effects of riboflavin plus UV treatment. The p38 and JNK signaling pathways were activated by GADD45α in RF-PRT-treated lymphocytes. These data revealed that RF-PRT effectively inhibited proliferation and induced apoptosis of lymphocytes by promoting GADD45α expression, which subsequently activates p38 and JNK signaling pathways. © 2016 AABB.

  16. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS

    2018-04-01

    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  17. Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

    Science.gov (United States)

    2017-01-01

    Cell proliferation is the common characteristic of all biological systems. The immune system insures the maintenance of body integrity on the basis of a continuous production of diversified T lymphocytes in the thymus. This involves processes of proliferation, differentiation, selection, death and migration of lymphocytes to peripheral tissues, where proliferation also occurs upon antigen recognition. Quantification of cell proliferation dynamics requires specific experimental methods and mathematical modelling. Here, we assess the impact of genetics and aging on the immune system by investigating the dynamics of proliferation of T lymphocytes across their differentiation through thymus and spleen in mice. Our investigation is based on single-cell multicolour flow cytometry analysis revealing the active incorporation of a thymidine analogue during S phase after pulse-chase-pulse experiments in vivo, versus cell DNA content. A generic mathematical model of state transition simulates through Ordinary Differential Equations (ODEs) the evolution of single cell behaviour during various durations of labelling. It allows us to fit our data, to deduce proliferation rates and estimate cell cycle durations in sub-populations. Our model is simple and flexible and is validated with other durations of pulse/chase experiments. Our results reveal that T cell proliferation is highly heterogeneous but with a specific “signature” that depends upon genetic origins, is specific to cell differentiation stages in thymus and spleen and is altered with age. In conclusion, our model allows us to infer proliferation rates and cell cycle phase durations from complex experimental 5-ethynyl-2'-deoxyuridine (EdU) data, revealing T cell proliferation heterogeneity and specific signatures. PMID:28288157

  18. T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

    International Nuclear Information System (INIS)

    Han, T.; Dadey, B.

    1978-01-01

    Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Comparison of the acute effects of radiation therapy including or excluding the thymus, on the lymphocyte subpopulations of cancer patients

    International Nuclear Information System (INIS)

    Stratton, J.A.; Byfield, P.E.; Byfield, J.E.; Small, R.C.; Benfield, J.; Pilch, Y.

    1975-01-01

    Radiation therapy to either mediastinum or pelvis causes a rapid decrease in circulating lymphocytes of both B and T types and in addition an impairment in the function of the remaining lymphocytes, as measured by their ability to proliferate in response to mitogens. The acute depression is short-lived. Substantial recovery is apparent within 3 wk after cessation of therapy; however, most patients show a modest, chronic depression in both numbers and functional capacities of circulating lymphocytes. T cells are somewhat more sensitive than B cells, but both are affected. Irradiation of the thymus per se seems to have little influence on the acute changes which occur, as patients receiving pelvic and mediastinal (including thymic) radiotherapy show a similar degree of lymphopenia and depression of lymphocyte responsiveness

  1. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

    Science.gov (United States)

    Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

    2017-03-09

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

  2. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    Science.gov (United States)

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  3. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Suping Ren

    Full Text Available Progestagen-associated endometrial protein (PAEP is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.

  4. 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.

  5. 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.

  6. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  7. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.

    2009-01-01

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  8. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  9. The cloning of T lymphocytes.

    Science.gov (United States)

    Schwartz, R H

    1982-02-01

    A new era of cellular immunology is clearly at hand. It is now possible, with a little bit of effort, to isolate monoclonal populations of T cells specific for any given antigen. The implications o f this technological advance are enormous in terms of applications to basic research and clinical medicine. In this article the two basic approaches that have been used to clone T lymphocytes are outlined, the pros and cons of each technique discussed and examples are given of recent experiments which have exploited this technology to gain new insights into T-cell specificity. Copyright © 1982. Published by Elsevier B.V.

  10. Dysregulation of T lymphocyte proliferative responses in autoimmunity.

    Directory of Open Access Journals (Sweden)

    Sydney K Elizer

    Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.

  11. Radiation-induced apoptosis of lymphocytes in peripheral blood

    International Nuclear Information System (INIS)

    Oh, Yoon Kyeong; Lee, Tae Bum; Nam, Taek Keun; Kee, Keun Hong; Choi, Cheol Hee

    2003-01-01

    This study quantitatively evaluated the apoptosis in human peripheral blood lymphocytes using flow cytometry, and investigated the possibility of using this method, with a small amount of blood, and the time and dose dependence of radiation-induced apoptosis. Peripheral blood lymphocytes were isolated from the heparinized venous blood of 11 healthy volunteers, 8 men and 3 women, with each 10 ml of blood being divided into 15 samples. The blood lymphocytes were irradiated using a linear accelerator at a dose rate of 2.4 Gy/min, to deliver doses of 0.5, 1, 2 and 5 Gy. The control samples, and irradiated cells, were maintained in culture medium for 24, 48 and 72 hours following the irradiation. The number of apoptotic cells after the in vitro X-irradiation was measured by flow cytometry after incubation periods of 24, 48 and 72 hours. We also observed the apoptotic cells using a DNA fragmentation assay and electron microscopy. The rate of spontaneous apoptosis increased in relation to the time interval following irradiation (1.761±0.161, 3.563±0.564, 11.098±2.849, at 24, 48, and 72 hours). The apoptotic cells also increased in the samples irradiated with 0.5, 1, 2 and 5 Gy, in a radiation dose and time interval after irradiation manner, with the apoptosis being too great at 72 hours after irradiation. The dose-response curves were characterized by an initial steep increase in the number of apoptotic cells for irradiation doses below 2 Gy, with a flattening of the curves as the dose approached towards 5 Gy. The flow cytometric assay technique yielded adequate data, and required less than 1 mL of blood. The time and dose dependence of the radiation-induced apoptosis, was also shown. It is suggested that the adequate time interval required for the evaluation of apoptosis would be 24 to 48 hours after blood sampling

  12. Cell Proliferation in Neuroblastoma

    Science.gov (United States)

    Stafman, Laura L.; Beierle, Elizabeth A.

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  13. anterior hyaloidal fibrovascular proliferation

    African Journals Online (AJOL)

    Okonkwo

    It most commonly occurs after phakic vitrectomy and scleral buckling for diabetic traction retinal detachment. It usually manifests with haemorrhage into the vitreous cavity or anterior hyaloid 3 to 12 weeks after vitrectomy and is the result of fibrovascular proliferation from the peripheral retina extending toward the equator of ...

  14. Peroxisome proliferator-activated receptor α-independent peroxisome proliferation

    International Nuclear Information System (INIS)

    Zhang Xiuguo; Tanaka, Naoki; Nakajima, Takero; Kamijo, Yuji; Gonzalez, Frank J.; Aoyama, Toshifumi

    2006-01-01

    Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor α (PPARα) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPARα-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPARα dependence in the assay system. Surprisingly, a novel type of PPARα-independent peroxisome proliferation and enlargement was uncovered in PPARα-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11α, might be associated with the PPARα-independent peroxisome proliferation at least in part

  15. Bilateral spontaneous carotid artery dissection.

    Science.gov (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis

    2005-06-01

    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  16. 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.

  17. Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells.

    Science.gov (United States)

    Huang, Hui-Wei; Zuo, Cong; Chen, Xiao; Peng, Yu-Ping; Qiu, Yi-Hua

    2016-08-01

    The aim of the present study was to examine the effect of the overexpression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines (CAs), in lymphocytes on the differentiation and function of T helper (Th) cells. A recombinant TH overexpression plasmid (pEGFP-N1-TH) was constructed and transfected into mesenteric lymphocytes using nucleofection technology. These cells were stimulated with concanavalin A (Con A) for 48 h and then examined for TH expression and CA content, as well as for the percentage of Th1 and Th2 cells, cytokine concentrations and for the levels of signaling molecules. The lymphocytes overexpressing TH also expressed higher mRNA and protein levels of TH, and synthesized more CAs, including norepinephrine (NE), epinephrine (E) and dopamine (DA) than the mock-transfected control cells. TH gene overexpression in the lymphocytes reduced the percentage of interferon-γ (IFN-γ)-producing CD4+ cells and the ratio of CD4+IFN-γ+/CD4+IL-4+ cells, as well as the percentages of CD4+CD26+ and CD4+CD30+ cells and the ratio of CD4+CD26+/CD4+CD30+ cells. TH overexpression also reduced the secretion of IFN-γ and tumor necrosis factor (TNF) from lymphocytes. Moreover, NE inhibited the Con A-induced lymphocyte proliferation and decreased both cyclic adenosine monophosphate (cAMP) levels and p38 mitogen-activated protein kinase (MAPK) expression in the lymphocytes. Our findings thus indicate that TH gene overexpression promotes the polarization and differentiation of CD4+ cells towards Th2 cells, and this effect is mediated by the cAMP and p38 MAPK signaling pathways.

  18. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan

    2010-12-01

    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  19. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  20. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  1. [Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

    The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

  2. Lymphocyte dynamics in healthy and lymphopenic conditions

    NARCIS (Netherlands)

    Hoeven, V. van

    2015-01-01

    By a balance of cell production and cell loss, B-cell and T-cell populations are generally maintained at a relatively stable size throughout life. Following lymphocyte-depleting therapies however, for example for the treatment of hematological malignancies, reconstitution of some lymphocyte subsets

  3. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  4. Proliferation in cycle

    Energy Technology Data Exchange (ETDEWEB)

    Piao Yunsong [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: yspiao@gucas.ac.cn

    2009-06-15

    In the contracting phase with w{approx_equal}0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w{approx_equal}0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

  5. JPRS Report, Proliferation Issues

    Science.gov (United States)

    1992-10-21

    Plutonium Cargo Rejected [LA TERCERA DE LA HORA 8 Oct] .................. 7 URUGUAY Nuclear Energy Agreement With Canada Shelved [BUSQUEDA 2 Oct...will monitor the shipment via there is concern over proliferation, such as South Africa, satellite, the Middle East and the Korean peninsula. As to the...Santiago IA TERCERA DE LA HORA national Affairs Commissions with the only opposition in Spanish 8 Oct 92 p 16 coming from the Herreraist faction congressmen

  6. 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

    Antigens of Plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the IgG fraction of the serum of an immune individual. The purified antigens induced proliferation of lymphocytes from persons who had recently had malaria. The ...... purified antigen preparations from malaria patients' sera indicating that significant amounts of non-specific mitogens were not present.......Antigens of Plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the IgG fraction of the serum of an immune individual. The purified antigens induced proliferation of lymphocytes from persons who had recently had malaria...

  7. [Advances in the treatment of chronic lymphocytic leukaemia].

    Science.gov (United States)

    Mozas, Pablo; Delgado, Julio

    2016-11-18

    Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. A method for prolonged imaging of motile lymphocytes.

    Science.gov (United States)

    Day, Daniel; Pham, Kim; Ludford-Menting, Mandy J; Oliaro, Jane; Izon, David; Russell, Sarah M; Gu, Min

    2009-02-01

    With new imaging technologies and fluorescent probes, live imaging of cells in vitro has revolutionized many aspects of cell biology. A key goal now is to develop systems to optimize in vitro imaging, which do not compromise the physiological relevance of the study. We have developed a methodology that contains non-adherent cells within the field of view. 'Cell paddocks' are created by generating an array of microgrids using polydimethylsiloxane. Each microgrid is up to 250 x 250 microm(2) with a height of 60 microm. Overlayed cells settle into the grids and the walls restrict their lateral movement, but a contiguous supply of medium between neighboring microgrids facilitates the exchange of cytokines and growth factors. This allows culture over at least 6 days with no impact upon viability and proliferation. Adaptations of the microgrids have enabled imaging and tracking of lymphocyte division through multiple generations of long-term interactions between T lymphocytes and dendritic cells, and of thymocyte-stromal cell interactions.

  9. Kinetics of the formation of a G2 block from tritiated thymidine in phytohemagglutinin-stimulated human lymphocytes

    International Nuclear Information System (INIS)

    Pollack, A.; Bagwell, C.B.; Irvin, G.L.; Jensen, J.A.

    1980-01-01

    Flow cytometry (FCM) was used to monitor the radiation effects promoted by incorporated tritiated thymidine ( 3 H-TdR) on phytohemagglutinin (PHA)-stimulated human peripheral blood lymphocytes stained with propidium iodide (PI). Lymphocyte microcultures were continuously labeled or pulse-labeled for various periods of time with different 3 H-TdR concentrations. Two types of DNA histogram analyses were performed on unperturbed and 3 H]TdR perturbed lymphocytes. The data analyses consisted of statistical analyses between averaged groups of histograms (nonparametric analysis) and cell cycle analyses (parametric analysis) to determine the percentages of cells in G0 + G1, S and G2 + M. The results showed that (a) 3 H-TdR when added to proliferating lymphocytes under certain conditions (both short-term continuous and pulse-labeling) caused a highly significant increase in the proportion of tetraploid (4C) cells by FCM, (b) the increase in the proportion of 4C cells represented a block in G2 and (c) the relative increase in the percentage of 4C cells was proportional to 3 H-TdR incorporation which was proportional to labeling time and concentration. Therefore, it was concluded that short labeling times be used to minimize adverse radiation effects when 3 H-TdR is used to assay substances affecting lymphocyte proliferation or in the estimation of cell cycle time

  10. Apoptosis induced by chlormethine and ionizing radiations in normal and tumoral lymphocytes: role of caspase-3

    International Nuclear Information System (INIS)

    Holl, V.P.

    2000-01-01

    Apoptosis can be induced by various stimuli like ionizing radiations or alkylating agents. Recent works have shown that apoptosis due to ionizing radiations can be initiated by DNA and cell membrane alterations, via radical species generation, implying the in fine activation of effector caspases, and in particular caspase-3. The main goal of this work is to clarify the role of caspase-3 in the radio-induced apoptosis mechanisms and to study the effects of apoptosis inhibition on the behaviour of the damaged cells. The effects of activation and caspase-3 activity inhibition on the progress of spontaneous, radio-induced or chlormethine-induced apoptosis have been evaluated for normal and tumoral lymphocytes. A chemical molecule, the ebselen, which can mime the action of the endogenous glutathione peroxidase, and a tetra-peptide inhibitor, AC-DEVD-CHO, selective of effector caspases, have been selected. The results indicate an inhibition by ebselen of all morphological and biochemical characteristics of chlormethine-induced apoptosis and a restoring of the cells viability. This seleno-organic compound also reduces the drop of the intra-cellular glutathione level and the loss of the trans-membrane potential (M) of the mitochondrion in the MOLT-4 tumoral cells treated with chlormethine. In parallel, the AC-DEVD-CHO effect on apoptosis induction has been tested. This inhibitor stops some chlormethine-induced criteria of apoptosis without affecting the final loss of the mitochondrial M and the cells proliferation. AC-DEVD-CHO has been also incubated just before the irradiation of the culture cells. The inhibition of the specific DEVD caspases prevents the inter-nucleosomal fragmentation of DNA and partially delays the externalization of phosphatidylserine without changing the viability of the irradiated cells. Moreover, the analysis of the AC-DEVD-CHO pre-treated irradiated cells floating on the surface shows a strong mitochondrial lactate dehydrogenase activity, which

  11. Proliferation after the Iraq war

    International Nuclear Information System (INIS)

    Daguzan, J.F.

    2004-09-01

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  12. Radiosensitiviness of blood lymphocytes from skin cancer patients and healthy volunteers as determined by micronucleus assay

    International Nuclear Information System (INIS)

    Lohmann, Tania Helena Ochi.

    1995-01-01

    Cancer, a major death cause in developed countries, has been related to somatic mutations that could be detected by cytogenetic analysis. Among the tools used in these tests, the micronucleus assay has been largely applied at population surveillance, biological dosimetry and early detection of groups with higher risks to developing cancers. In this study, we analysed the chromosome susceptibility of blood lymphocytes from basocellular skin cancer patients and healthy volunteers. The cytogenetic analysis was performed by a micronucleus assay, using progressive doses of ionizing radiation from a 60 Co source as mutagen. Briefly, the blood lymphocytes were irradiated in vitro, as processed by the cytokinesis-blocked method. The micronucleus frequency and distribution, cell cycle kinetics, nucleation index and dose-response relationship were determined in each patient. The results showed that the basocellular skin cancer patients lymphocytes presented higher spontaneous micronucleus frequency as compared with those from healthy young volunteers but lower than healthy now young volunteers . The radiation-induced micronucleus analysis showed that the basocellular skin cancer patients' lymphocytes presented similar proportion of damage lymphocytes as compared with those from healthy volunteers. Nevertheless, the magnitude of this damage was higher in this group with doses. Higher than 400 c Gy, which was not occurred in healthy volunteers. Cell cycle kinetics, as determined by the nucleation index, was lower in basocellular skin cancer patients as compared with healthy volunteers, indicating a more slow cell cycle. Our data showed that the lymphocytes from carcinoma basocellular patients were more radiosensitive as compared with those form healthy volunteers. (author). 159 refs., 21 figs., 16 tabs

  13. A novel method for producing target cells and assessing cytotoxic T lymphocyte activity in outbred hosts

    Directory of Open Access Journals (Sweden)

    Bendinelli Mauro

    2009-03-01

    Full Text Available Abstract Background Cytotoxic T lymphocytes play a crucial role in the immunological control of microbial infections and in the design of vaccines and immunotherapies. Measurement of cytotoxic T lymphocyte activity requires that the test antigen is presented by target cells having the same or compatible class I major hystocompatibility complex antigens as the effector cells. Conventional assays use target cells labeled with 51chromium and infer cytotoxic T lymphocyte activity by measuring the isotope released by the target cells lysed following incubation with antigen-specific cytotoxic T lymphocytes. This assay is sensitive but needs manipulation and disposal of hazardous radioactive reagents and provides a bulk estimate of the reporter released, which may be influenced by spontaneous release of the label and other poorly controllable variables. Here we describe a novel method for producing target in outbred hosts and assessing cytotoxic T lymphocyte activity by flow cytometry. Results The method consists of culturing skin fibroblasts, immortalizing them with a replication defective clone of simian virus 40, and finally transducing them with a bicistronic vector encoding the target antigen and the reporter green fluorescent protein. When used in a flow cytometry-based assay, the target cells obtained with this method proved valuable for assessing the viral envelope protein specific cytotoxic T lymphocyte activity in domestic cats acutely or chronically infected with feline immunodeficiency virus, a lentivirus similar to human immunodeficiency virus and used as animal model for AIDS studies. Conclusion Given the versatility of the bicistronic vector used, its ability to deliver multiple and large transgenes in target cells, and its extremely wide cell specificity when pseudotyped with the vesicular stomatitis virus envelope protein, the method is potentially exploitable in many animal species.

  14. Apoptotic response of irradiated T-Lymphocytes. An epidemiologic study in canine radiotherapy patients

    International Nuclear Information System (INIS)

    Stankeova, S.; Kaser-Hotz, B.; Crompton, N.E.A.; Blattmann, H.; Theiler, P.; Emery, G.C.; Roos, M.

    2003-01-01

    Background: Evaluation of radiation-induced apoptosis in T-lymphocytes was developed for human medicine in order to predict the sensitivity of individual patients to radiation therapy and has regular use in cases of suspected hypersensitivity. A major goal of the present study was to evaluate the usefulness of the apoptosis assay in veterinary medicine for application in radiation sensitivity testing. The main goal was to examine potential changes in sensitivity of T-lymphocytes to radiation-induced apoptosis during the course of radiation treatment. This is a clear example of the advantageous use of spontaneous canine tumors to augment human cancer research. Material and Methods: Blood was collected in heparin tubes, diluted 1:10 in RPMI medium, irradiated with X-rays and incubated for 48 h. T-lymphocytes were labeled using FITC-conjugated antibodies, erythrocytes were lysed, and DNA stained with propidium iodide. For cell analysis, a Becton Dickinson FACScan flow cytometer was used. Radiation-induced apoptosis in T-lymphocytes was quantified. Blood samples from tumor-bearing dogs were taken before the first fraction and at the end of radiation therapy. Results: Apoptosis in lymphocytes is dependent on donor age and donor weight. Tumor-bearing dogs when compared with healthy dogs showed no significant differences in levels of induced apoptosis. No significant changes were seen in the levels of radiation-induced apoptosis in blood taken before, during, or after radiation therapy. Conclusion: The leukocyte apoptosis assay can be successfully applied to canine patients, and a wide spectrum of sensitivities to radiation-induced apoptosis is observed. The sensitivity of a patient's peripheral blood T-lymphocytes to radiation-induced apoptosis does not change as a result of the trauma of radiotherapy during the course of tumor treatment. (orig.)

  15. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  16. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation.

    Directory of Open Access Journals (Sweden)

    Zhilong Li

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.

  17. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  18. The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients.

    Science.gov (United States)

    Huang, Sha-Sha; He, Si-Li; Zhang, Yuan-Ming

    2016-01-01

    Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China. T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively. There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls. Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients. © The Author(s) 2016.

  19. Can we predict nuclear proliferation

    International Nuclear Information System (INIS)

    Tertrais, Bruno

    2011-01-01

    The author aims at improving nuclear proliferation prediction capacities, i.e. the capacities to identify countries susceptible to acquire nuclear weapons, to interpret sensitive activities, and to assess nuclear program modalities. He first proposes a retrospective assessment of counter-proliferation actions since 1945. Then, based on academic studies, he analyzes what causes and motivates proliferation, with notably the possibility of existence of a chain phenomenon (mechanisms driving from one program to another). He makes recommendations for a global approach to proliferation prediction, and proposes proliferation indices and indicators

  20. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.

    1983-01-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  1. Optical antenna enhanced spontaneous emission.

    Science.gov (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  2. JPRS Report, Proliferation Issues

    Science.gov (United States)

    1992-05-27

    JPRS-TND-92-016 27 MAY 1992 JPRS Repor Proliferation Issues ÄBpxovea tcz pursue ieiaaM| Ipfe. fötmbuasa OsüoaÜBd .^L ■ — —— au »** 19980112...6 MOROCCO Berrada on Proposed Nuclear Power Plant [ MAROC SOIR 22 Apr] 6 JPRS-TND-92-016 27 May 1992 2 CENTRAL EURASIA Proposals on...three days of talks here on normalizing relations with Japan, which were largely stalemated over Tokyo’s demand for Pyongyang’s assurance that it did

  3. Experimental porcine eperythrozoonosis: T-lymphocyte suppression and misdirected immune responses.

    Science.gov (United States)

    Zachary, J F; Smith, A R

    1985-04-01

    Immune responses and hematologic alterations were investigated in splenectomized pigs after IM inoculation with Eperythrozoon suis. Early hematologic alterations were massive parasitism of RBC, severe hypoglycemia, moderate bilirubinemia, and mild anemia; later findings included severe anemia, minimal parasitism of RBC, spontaneous agglutination of RBC at 25 C and 4 C which was reversible at 37 C, transient thrombocytopenia, and mild bilirubinemia. The humoral immune responses consisting of a transitory hyperglobulinemia and increase of indirect hemagglutination (IHA) titers against E suis were attributed to immunoglobulin M cold agglutinins. Cell-mediated immune responses, measured by phytohemagglutinin- and pokeweed mitogen-induced lymphocyte blastogenesis, were reduced after massive parasitemia. Blastogenesis induced by Escherichia coli lipopolysaccharide mitogen was increased before the hyperglobulinemia and an increase in IHA titer. There was an increase in the uptake of [3H]thymidine by lymphocytes cultured without mitogens after the decline in total globulin concentration and IHA titer.

  4. Lymphocytic Pleural Effusion in Acute Melioidosis

    Directory of Open Access Journals (Sweden)

    Kuo-Mou Chung

    2007-10-01

    Full Text Available An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.

  5. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.

    1997-01-01

    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  6. CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells

    Science.gov (United States)

    Sarin, Ritu

    2012-01-01

    Lymphocyte numbers are tightly regulated; with acute lymphopenia, T cell numbers are reestablished through lymphopenia-induced proliferation. In contrast to the costimulation requirements of antigen-driven proliferation, a number of costimulatory molecules are not required for lymphopenia-induced proliferation. However, the requirement for major histocompatibility complex (MHC)-T cell receptor (TCR) interactions and the enhanced lymphopenia-induced proliferation in T cells with higher TCR affinity argue for a role for surface molecules that contribute to efficient MHC-TCR interactions, in particular adhesion molecules. CD18 is an integrin that contributes to the activation of peripheral and intestinal T cells through adhesive and costimulatory mechanisms. We found that CD18 is required for optimal polyclonal and monoclonal CD4+ T cell lymphopenia-induced proliferation in recombination-activating gene 1-deficient (RAG-1−/−) mice; this requirement persisted over time. Uniquely, the dependency on CD18 in CD4+ T cells is in the rapid proliferation in RAG-1−/− recipients and in the slow homeostatic proliferation in irradiated Balb/c recipients. Consistent with the proposed role for intestinal microbiota in lymphopenia-induced rapid proliferation in RAG−/− mice, we observed a significant reduction in rapid proliferation upon treatment of mice with antibiotics; however, the dependency on CD18 for optimal lymphopenia-induced proliferation persisted. Moreover, the dependency for CD18 is maintained over a wide range of numbers of initially transferred T cells, including a low number of initially transferred T cells, when the drive for proliferation is very strong and proliferation is more rapid. Overall, these data argue for an essential and broad role for CD18 in lymphopenia-induced proliferation. PMID:22821945

  7. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    OpenAIRE

    Kuender D. Yang; Kuender D. Yang; Kuender D. Yang; Te-Yao Hsu; Hong-Ren Yu; Ching-Chang Tsai; Ling-Sai Chang; Hsin-Chun Huang; Hsin-Hsin Cheng; Jiu-Yao Wang; Jiu-Yao Wang; Jiunn-Ming Sheen; Ho-Chang Kuo; Kai-Sheng Hsieh; Ying-Hsien Huang

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhance...

  8. Initiatives for proliferation prevention

    International Nuclear Information System (INIS)

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy's (DOE's) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway

  9. Non Proliferation of Nuclear

    International Nuclear Information System (INIS)

    Bambang S Irawan

    2004-01-01

    Non-Proliferation Treaty of Nuclear Weapons is the international community's efforts to maintain the security of the world, in order to prevent the spread of nuclear technology and the use of nuclear weapons, promoting cooperation for the use of nuclear peaceful purposes, build mutual trust (Confidence Building Measures) as well as to achieve the ultimate goal of disarmament overall (General and Complete Disarmament). Addressing the post-WTC tragedy, 11 September 2001, the Indonesian government should set up a National Measures (National Action Plan), among others formed the National Security Council and NBC Counter Proliferation Unit, or the National Authority for Nuclear Treaty, preparing national legislation, to prevent the abuse nuclear materials for terrorist acts, prevent Illicit Trafficking of Nuclear materials, developed a National Preparedness and Emergency Response Management in the event of a nuclear accident or attack by the use of nuclear terrorism. Importance of a National Action Plan meant the existence of a national commitment in the context of compliance with treaties and conventions which have been ratified relating to safety, security, safeguards towards a general and complete disarmament, to safeguard national security and maintain peace (safeguards) international

  10. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2011-01-01

    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  11. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)

    2007-11-15

    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  12. Functional studies on lymphocytes from two siblings with congential hypogammaglobulinaemia

    International Nuclear Information System (INIS)

    Tauris, P.; Wendelboe Hansen, P.

    1983-01-01

    Two brothers with hypogammaglobulinaemia classified as common variable immunodeficiency (CVID) were investigated for distribution of pheripheral blood lymphocyte (PBL) subpopulations, DNA synthesis and plaque-forming cell (PFC) capability of pokeweed mitogen (PWM) activated autologous and allogenic cocultures. Both patients had a decreased absolute number of T cells and normal or elevated levels of surface immunoglobulin (SmIg) bearing cells. Isolated B cells cocultured with autologous or allogeneic 4000 r irradiated T cells responded subnormally to PWM monitored by the 3 H-thymidine incorporation in microcultures whereas B cells cocultured with allogeneic untreated normal T cells proliferated normally. PBL from parallel macrocultures of unfractionated or T/B separated patients' cells were not able to produce plaques using a reversed haemolytic protein A assay. Addition of glucocorticoid to unfractionated PBL did not reverse the unresponsiveness. In allogeneic cocultures patients' untreated or 2000 r irradiated T cells induced a normal PFC response. Normal untreated T cells induced a reduced number of IgM- and IgG-PFC from patients' B cells but this response was almost eliminated using irradiated normal T cells. These results demonstrate a primary B cell defect in the patients and indicate an impaired cooperation between patients' B and T cells. Activation of patients' B cells to Ig secretion requires the presence of proliferating T cells. (author)

  13. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  14. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

    2011-01-01

    Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  15. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kukat, Alexandra [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Edgar, Daniel [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Bratic, Ivana [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Maiti, Priyanka [Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Trifunovic, Aleksandra, E-mail: aleksandra.trifunovic@ki.se [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany)

    2011-06-10

    Highlights: {yields} Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. {yields} This process is independent of endogenous ROS production. {yields} Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O{sub 2}) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  16. Leukocytosis, muscle damage and increased lymphocyte proliferative response after an adventure sprint race

    Directory of Open Access Journals (Sweden)

    R. Tossige-Gomes

    2014-06-01

    Full Text Available The effect of an adventure sprint race (ASR on T-cell proliferation, leukocyte count and muscle damage was evaluated. Seven young male runners completed an ASR in the region of Serra do Espinhaço, Brazil. The race induced a strong leukocytosis (6.22±2.04×103 cells/mm3 before vs 14.81±3.53×103 cells/mm3 after the race, marked by a significant increase of neutrophils and monocytes (P<0.05, but not total lymphocytes, CD3+CD4+ or CD3+CD8+ cells. However, the T-cell proliferative response to mitogenic stimulation was increased (P=0.025 after the race, which contradicted our hypothesis that ASR, as a high-demand competition, would inhibit T-cell proliferation. A positive correlation (P=0.03, r=0.79 was observed between the proliferative response of lymphocytes after the race and the time to complete the race, suggesting that the proliferative response was dependent on exercise intensity. Muscle damage was evident after the race by increased serum levels of aspartate amino transferase (24.99±8.30 vs 50.61±15.76 U/L, P=0.003. The results suggest that humoral factors and substances released by damaged muscle may be responsible for lymphocyte activation, which may be involved in muscle recovery and repair.

  17. Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell proliferation and survival

    DEFF Research Database (Denmark)

    Doyle, I S; Hollmann, C A; Crispe, I N

    2001-01-01

    Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted a...

  18. Lymphocytic Meningitis in Patients with Sympathetic Ophthalmia.

    Science.gov (United States)

    Goudot, Mathilde; Groh, Matthieu; Salah, Sawsen; Monnet, Dominique; Blanche, Philippe; Brézin, Antoine P

    2017-04-01

    This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm 3 . The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.

  19. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  20. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  1. General Information about Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  2. Chronic Lymphocytic Leukemia: Current Concepts.

    Science.gov (United States)

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

    2015-10-01

    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    Pohajdak, B.; Gomez, J.; Orr, F.W.; Khalil, N.; Talgoy, M.; Greenberg, A.H.

    1986-01-01

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1 + cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML( 3 H)P, suggesting that LGL bear receptors for the chemotactic peptide

  4. How T lymphocytes see antigen

    Science.gov (United States)

    Chakraborty, Arup K.

    2009-03-01

    Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.

  5. LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    E. V. Abakushina

    2014-01-01

    Full Text Available The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69 before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+ (р < 0,05. However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05. Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

  6. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen

    2016-01-01

    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  7. Orbital involvement in chronic lymphocytic leukemia.

    Science.gov (United States)

    Skinnider, L F; Romanchuk, K G

    1984-04-01

    In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults.

  8. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

    Stelmachowska, M.; Bolko, P.; Wasko, R.; Sowinski, J.; Kosinski, D.; Towpik, I.

    2006-01-01

    Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

  9. Morphometric model of lymphocyte as applied to scanning flow cytometry

    Science.gov (United States)

    Loiko, Valery A.; Ruban, Gennady I.; Gritsai, Olga A.; Gruzdev, Alexey D.; Kosmacheva, Svetlana M.; Goncharova, Natalia V.; Miskevich, Alexander A.

    2006-11-01

    The peripheral blood lymphocytes of normal individuals are investigated by methods of specialized light microscopy. Lymphocytes as a whole and T-cell subpopulation are considered. Lymphocyte structure is characterized with reference to polarizing scanning flow cytometry. The lymphocyte and lymphocyte nucleus shapes are analyzed. Linear correlation dependence between sizes of lymphocyte and its nucleus is indicated. A morphometric model of a lymphocyte is constructed using the obtained data. The findings can be used, for instance, as input parameters to solve the direct and inverse light-scattering problems of turbidimetry, nephelometry, and flow cytometry.

  10. The changing proliferation threat

    Energy Technology Data Exchange (ETDEWEB)

    Sopko, J.F.

    1996-12-31

    Technological advances and new adversaries with new motives have reduced the relevancy and effectiveness of the American nonproliferation strategy that was developed during the Cold War. The Cold War`s end and the breakup of the Soviet Union have created new proliferation dangers even as they have reduced others. The familiar balance of nuclear terror that linked the superpowers and their client states for nearly 50 years in a choreographed series of confrontations has given way to a much less predictable situation, where weapons of unthinkable power appear within the grasp of those more willing to use them. Rogue nations and {open_quotes}clientless{close_quotes} states, terrorist groups, religious cults, ethnic minorities, disaffected political groups, and even individuals appear to have jointed a new arms race toward mass destruction. The author describes recent events that suggest the new trends and a serious challenge to US national security.

  11. The nuclear proliferation

    International Nuclear Information System (INIS)

    Gere, F.

    1995-04-01

    In this book is detailed the beginning of nuclear military power, with the first bomb of Hiroshima, the different ways of getting uranium 235 and plutonium 239, and how the first countries (Usa, Ussr, China, United kingdom, France) got nuclear weapons. Then the most important part is reviewed with the details of non-proliferation treaty and the creation of IAEA to promote civilian nuclear power in the world and to control the use of plutonium and uranium in nuclear power plants. The cases of countries who reached the atom mastery, such Israel, South Africa, Pakistan, Iraq, North Korea, Argentina, Brazil, Iran, Algeria, Taiwan and the reasons which they wanted nuclear weapon for or why they gave up, are exposed

  12. 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.

  13. Lymphocyte proliferative responses to mitogens in rats having an ancestry of a perinatal iodine-131 insult

    International Nuclear Information System (INIS)

    Stevens, R.H.; Cheng, H.F.

    1987-01-01

    The possible existence of a genealogical memory consisting of altered lymphocyte proliferative responses to a perinatal iodine-131 insult has been investigated in two generations of inbred Fischer F344 rat offspring. The studies which involved exposure to the radioiodine during late pregnancy with concentrations ranging from 1.85 MBq (50 μCi) to 7.4 MBq (200 μCi) revealed that only the peripheral blood T lymphocytes of the first generation male animals were significantly affected. These animals were found to possess T lymphocytes which exhibited increased proliferative responses expressed toward the mitogens concanavalin A and phytohemagglutin; however, no significant changes were noticeable in their B cell population following exposure to lipopolysaccharide. Neither the first generation females nor the male and female offspring of the second generation developed through sibling interbreeding seemed to be affected, this was unlike the cellular, humoral, and natural immunity which had previously been observed to be changed in both the second and third generation animals. These observations suggest that the effects of the radiation insult upon immunocompetency as measured by lymphocyte proliferation do not appear to be inherited

  14. Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression by Ganoderma Lucidum Polysaccharides

    Directory of Open Access Journals (Sweden)

    Li-Xin Sun

    2014-01-01

    Full Text Available Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

  15. Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase

    International Nuclear Information System (INIS)

    Knox, S.; Misra, H.P.; Shifrine, M.

    1982-01-01

    Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 μg catalase or 100 μg SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p 2 - and/or H 2 O 2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis. (author)

  16. Cytogenetic analysis of Greek farmers using the micronucleus assay in peripheral lymphocytes and buccal cells.

    Science.gov (United States)

    Pastor, S; Gutiérrez, S; Creus, A; Xamena, N; Piperakis, S; Marcos, R

    2001-11-01

    The potential cytogenetic damage associated with pesticide use in Greek agricultural workers was evaluated using micronuclei (MN) as biomarkers in lymphocytes of peripheral blood and exfoliated cells of the buccal mucosa. In addition, the effects of pesticide exposure and other variables on the cytokinesis block proliferation index (CBPI) in lymphocytes were also evaluated. Both the exposed and control individuals were selected from Nea Makri, a village near Athens (Greece). This location was selected for its high greenhouse density. Micronuclei were analysed in 50 agricultural workers exposed to pesticides (30 men and 20 women) and in 66 non-exposed individuals that constituted the control group (41 men and 25 women). The comparison between workers and controls did not reveal any statistical significant difference in the MN frequency for either lymphocytes or buccal cells. Nevertheless, the multiple regression analysis revealed that the age and the interaction between gender and the number of X-ray examinations during the last 3 years preceding the sampling increased the number of MN in lymphocytes. Moreover, the results of the negative binomial regression analysis suggested that the level of MN in buccal cells could be reduced by the intake of fish, whilst being increased by olive oil consumption. Regarding CBPI, the value found in the exposed group was lower than in controls, the difference being statistically significant. On the other hand, CBPI was inversely associated with both age and X-ray exposure.

  17. Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing.

    Science.gov (United States)

    Xiang, Quan-Dan; Yu, Qiang; Wang, Hui; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2017-07-05

    Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca 2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca 2+ /CaN and MAPK pathways play essential roles.

  18. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.

    1994-01-01

    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  19. Spontaneous Development of Moral Concepts

    Science.gov (United States)

    Siegal, M.

    1975-01-01

    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  20. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter

    2013-01-01

    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  1. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien

    2002-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  2. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  3. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  4. Proliferation and apoptosis in infection with infectious bursal disease virus: a flow cytometric study.

    Science.gov (United States)

    Ojeda, F; Skardova, I; Guarda, M I; Ulloa, J; Folch, H

    1997-01-01

    Programmed cell death, or apoptosis, is involved in the normal physiology of many immunocompetent organs, including lymphocytes of the bursa of Fabricius in chickens. Involvement of apoptosis has also been described in some viral diseases such as AIDS. The purpose of this work was to study the potential role of apoptosis in the pathogenesis of Gumboro disease in the bursa of Fabricius. Our results show that 1-3 days after infection of young chickens with infectious bursal disease virus, the number of apoptotic cells increases and cellularity and proliferation decrease. Because of the dynamic nature of bursal lymphocyte populations and the involvement of apoptosis in lymphocyte cell physiology, the increased level of cells undergoing apoptosis may be due to an impairment in the withdrawal of apoptotic cells. A concomitant increase in macrophages in infected bursae and a dramatic decrease in cellularity suggest that an increase in apoptosis may be an important cause of cell depletion.

  5. T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

    Directory of Open Access Journals (Sweden)

    Malika Trad

    2015-01-01

    Full Text Available T lymphocytes activated by dendritic cells (DC which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

  6. T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

    Science.gov (United States)

    Trad, Malika; Gautheron, Alexandrine; Fraszczak, Jennifer; Larmonier, Claire; LaCasse, Collin J.; Centuori, Sara; Audia, Sylvain; Samson, Maxime; Ciudad, Marion; Bonnefoy, Francis; Lemaire-Ewing, Stéphanie; Katsanis, Emmanuel; Perruche, Sylvain; Saas, Philippe; Bonnotte, Bernard

    2015-01-01

    T lymphocytes activated by dendritic cells (DC) which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC) are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme. PMID:26491691

  7. B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

    International Nuclear Information System (INIS)

    Reddy, M.M.; Goh, K.; Hempelmann, L.H.

    1976-01-01

    B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

  8. Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell proliferation and survival

    DEFF Research Database (Denmark)

    Doyle, I S; Hollmann, C A; Crispe, I N

    2001-01-01

    Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted...... these effects. Addition of BCR or IL-4 signals did not overcome the effect of ICAM-1 or MHC II on CD40-induced proliferation. FasL expression was not detected in B cell populations. These results show that MHC II and ICAM-1 specifically modulate CD40-mediated signaling, so inhibiting proliferation...

  9. Enhanced MTT-reducing activity under growth inhibition by resveratrol in CEM-C7H2 lymphocytic leukemia cells.

    Science.gov (United States)

    Bernhard, David; Schwaiger, Wolfgang; Crazzolara, Roman; Tinhofer, Inge; Kofler, Reinhard; Csordas, Adam

    2003-06-10

    Inhibition of proliferation by resveratrol of CEM-C7H2 lymphocytic leukemia cells was paradoxically associated with an enhanced cellular 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-reducing activity. This phenomenon was most pronounced at the sub-apoptotic concentration range of 5-20 microM resveratrol. The results of our study show that the MTT-reducing activity can be increased by the polyphenolic antioxidant resveratrol without a corresponding increase in the number of living cells and that this occurs at a concentration range of the antioxidant which is not sufficient to induce apoptosis but suffices to slow down cell growth. This phenomenon appears to be restricted to proliferation inhibitors with antioxidant properties and is cell type-specific. Thus, in determining the effects of flavonoids and polyphenols on proliferation, in certain cell types this might represent a pitfall in the MTT proliferation assay.

  10. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

    Directory of Open Access Journals (Sweden)

    Finnegan Alison

    2008-02-01

    Full Text Available Abstract Background All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s, particularly T-helper type 1 (Th1 responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs. We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. Methods Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8 were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15 with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49–80. Group 1 subjects' lymphocyte proliferation response to Aluminum+3, Cobalt+2, Chromium+3, Copper+2, Iron+3, Molybdenum+5, Manganeese+2, Nickel+2, Vanadium+3 and Sodium+2 chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl3, 0.1 mM NiCl2, 0.1 mM CoCl2 and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. Results Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p 2 fold stimulation index response, p 10 mM. The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes

  11. Equine peripheral blood mononuclear cells proliferate in response to tetanus toxoid antigen.

    Science.gov (United States)

    McKelvie, J; Little, S; Foster, A P; Cunningham, F M; Hamblin, A

    1998-01-01

    It has been reported that equine peripheral blood mononuclear cells (PBMNs) do not proliferate in response to tetanus toxoid (TT) (Frayne and Stokes 1995, Research in Veterinary Science 59, 79-81). Here we demonstrate that lymphocyte proliferation responses to TT, which are characteristic of a recall antigen, may be achieved under certain culture conditions. Given that TT vaccination is routinely applied to many horses, TT is a suitable antigen for the investigation of cellular immune responses by peripheral blood mononuclear cells in the horse.

  12. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  13. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  14. Chronic granulomatous pneumonia and lymphocytic responses induced by inhaled beryllium metal in A/J and C3H/HeJ mice

    Energy Technology Data Exchange (ETDEWEB)

    Nikula, K.J.; Swafford, D.S.; Hoover, M.D.; Tohulka, M.D.; Finch, G.L. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)

    1997-12-31

    Inhalation of beryllium (Be) has been associated with 2 syndromes: an acute chemical pneumonitis and a granulomatous lung disease known as chronic beryllium disease (CBD). The purpose of this study was to establish a mouse model of CBD using the inhalation route of exposure. A/J (H-2a haplotype) and C3H/HeJ (H-2{sup k}) Mice were exposed once for 90 min in nose-only exposure tubes to aerosols of Be metal. Six mo later, lung histopathologic responses were assessed. Further analyses defined the phenotypic profile of lymphocytes in pulmonary lesions and evaluated proliferation of lymphocytes in situ and in response to Be in vitro. Responses were similar in both strains of mice. Most Be-exposed mice had minimal to mild interstitial fibrosis. The majority of lymphocytes in interstitial infiltrates and in microgranulomas were CD4+ T cells. Interstitial compact aggregates of lymphocytes contained B cells centrally and CD4+ cells peripherally. Lymphocyte labeling indices, used to assess proliferation in situ, were significantly greater within microgranulomas compared to compact lymphocytic aggregates. Lymphocyte stimulation indices in response to BeSO{sub 4} in vitro were not positive in blood, spleen, or tracheobronchial lymph node samples. Be-specific immune responses and nonspecific inflammatory responses to toxic and foreign-body properties of Be may have contributed to the histopathology in both strains of mice. The interstitial mononuclear cell infiltrates, presence of microgranulomas, multinucleated foreign-body and Langhans giant cells, interstitial fibrosis, and CD4+ T-cell predominance with local proliferation are features similar to CBD in humans. The chronic lung disease induced in these mice by inhaled Be can be used to investigate the importance of variables such as dose, exposure pattern, and physicochemical form of Be in producing this disease. 29 refs., 6 figs., 3 tabs.

  15. Chronic granulomatous pneumonia and lymphocytic responses induced by inhaled beryllium metal in A/J and C3H/HeJ mice

    International Nuclear Information System (INIS)

    Nikula, K.J.; Swafford, D.S.; Hoover, M.D.; Tohulka, M.D.; Finch, G.L.

    1997-01-01

    Inhalation of beryllium (Be) has been associated with 2 syndromes: an acute chemical pneumonitis and a granulomatous lung disease known as chronic beryllium disease (CBD). The purpose of this study was to establish a mouse model of CBD using the inhalation route of exposure. A/J (H-2a haplotype) and C3H/HeJ (H-2 k ) Mice were exposed once for 90 min in nose-only exposure tubes to aerosols of Be metal. Six mo later, lung histopathologic responses were assessed. Further analyses defined the phenotypic profile of lymphocytes in pulmonary lesions and evaluated proliferation of lymphocytes in situ and in response to Be in vitro. Responses were similar in both strains of mice. Most Be-exposed mice had minimal to mild interstitial fibrosis. The majority of lymphocytes in interstitial infiltrates and in microgranulomas were CD4+ T cells. Interstitial compact aggregates of lymphocytes contained B cells centrally and CD4+ cells peripherally. Lymphocyte labeling indices, used to assess proliferation in situ, were significantly greater within microgranulomas compared to compact lymphocytic aggregates. Lymphocyte stimulation indices in response to BeSO 4 in vitro were not positive in blood, spleen, or tracheobronchial lymph node samples. Be-specific immune responses and nonspecific inflammatory responses to toxic and foreign-body properties of Be may have contributed to the histopathology in both strains of mice. The interstitial mononuclear cell infiltrates, presence of microgranulomas, multinucleated foreign-body and Langhans giant cells, interstitial fibrosis, and CD4+ T-cell predominance with local proliferation are features similar to CBD in humans. The chronic lung disease induced in these mice by inhaled Be can be used to investigate the importance of variables such as dose, exposure pattern, and physicochemical form of Be in producing this disease. 29 refs., 6 figs., 3 tabs

  16. Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

    NARCIS (Netherlands)

    Baert, F.; Wouters, K.; D'Haens, G.; Hoang, P.; Naegels, S.; D'Heygere, F.; Holvoet, J.; Louis, E.; Devos, M.; Geboes, K.

    1999-01-01

    It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis.

  17. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

    Directory of Open Access Journals (Sweden)

    Caimi Luigi

    2010-11-01

    Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

  18. 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.

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

    Science.gov (United States)

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

    2017-03-01

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

  20. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    (PHA)-stimulation. Induced CD25 expression in response to stimulation was lower in patient cells than in donor cells (in CD4+ (p = 0.01) and in CD8+ (p = 0.03)). After rlL-2 treatment, the functionality of ex vivo expanded PBMC from patients was restored to the level found in donors. Finally......, the induced gene expressions for IL-2 and IL-2R were positively correlated (p genes in humans may share a common activation pathway, as has been found in monkeys infected by simian immunodeficiency virus (SIV). These results indicate...

  1. Cyclooxygenases: Proliferation and differentiation | Rastegar ...

    African Journals Online (AJOL)

    ... tissues and is highly inducible by growth factors, cytokines, and tumour promoters. In several studies, the effect of cyclooxygenases on different cell types has been investigated. This review focuses on cyclooxygenases function, cell proliferation and differentiation. Key words: Cyclooxygenases, proliferation, differentiation, ...

  2. Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients

    Directory of Open Access Journals (Sweden)

    Ahad Zare

    2013-01-01

    Full Text Available Background: Immunotherapy with paternal lymphocytes plays an important role in preventing recurrent spontaneous abortion (RSA and is an effective treatment for it. This kind of treatment is performed as an immunotherapy method in several centers in the world. It attributes to the production of anti-paternal cytotoxic antibodies (APCAs in women with RSA. Production of APCA after lymphocyte immunotherapy (LIT in RSA patients gives them a better chance for successful pregnancy. Regarding the important effect of trace elements on the function of the immune system, we tried to investigate the correlation between serum zinc level and the success of LIT in RSA. Materials and Methods: Serum zinc concentration was determined in two groups of RSA patients using atomic absorption spectrophotometer systems. Group (a that responded to the paternal lymphocytes and their cross-match test was positive, and group (b that had no response to the paternal lymphocytes immunizations and their cross-match test was negative. Results: Serum zinc levels in group (a patients were 74.98 ± 11.88 μg/dl, which was significantly higher than those in group (b with the zinc concentration of 64.22 ± 9.22 μg/dl. Conclusions: Zinc deficiency may be one of the substantial causes of negative results for LIT in RSA patients. Therefore, compensation of zinc defect before LIT can be a promising approach to improve the immune response in patients.

  3. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota

    2000-01-01

    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  4. Lymphocyte fluctuation in bronchoalveolar lavage fluid in normal volunteers.

    Science.gov (United States)

    Laviolette, M

    1985-01-01

    In an attempt to understand the widely varying bronchoalveolar lavage lymphocyte counts reported in normal subjects, we performed bronchoalveolar lavage in 42 healthy nonsmokers. The mean (SD) lymphocyte percentage in this first lavage was 9.6% (7.7%). The values did not fit a normal distribution. Five subjects had more than 20% of lymphocytes, and when they were excluded the distribution of lymphocyte counts was normal. Bronchoalveolar lavage was repeated once or twice in these five subjects 47 days or more after the previous lavage and the lymphocyte count decreased below 14% in four. Eight volunteers with an initial lymphocyte percentage less than 20% also had repeat lavages; two presented a transient increase of lymphocyte count above 20%. These data show that the percentage of lymphocytes in lavage fluid fluctuates significantly in normal subjects and suggest that lymphocyte counts counts higher than 14% should not be considered as normal. PMID:4060105

  5. Nuclear proliferation: linkages and solutions

    International Nuclear Information System (INIS)

    Quester, G.H.

    1979-01-01

    Nuclear proliferation must be periodically re-examined as a moral as well as a practical foreign policy dilemma. The question is asked whether proliferation precludes a safe and peaceful world, or if a halt to proliferation is adequate without other arms control. The moral dilemma in foreign policy arises over the need to make practical choices which often serve one goal while sacrificing another. The ramifications of nuclear proliferation are examined and the conclusions reached that it is not an acceptable option. It is also decided that, because general disarmament steps will be more difficult to achieve, the world may have to accept a small number of nuclear arsenals as the price of state sovereignties. A high priority for making the effort to prevent proliferation is advised. 8 references

  6. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.

    1985-08-01

    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  7. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain

    2011-03-01

    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  8. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Management of intractable spontaneous epistaxis

    Science.gov (United States)

    Rudmik, Luke

    2012-01-01

    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  10. Modeling adenovirus latency in human lymphocyte cell lines.

    Science.gov (United States)

    Zhang, Yange; Huang, Wen; Ornelles, David A; Gooding, Linda R

    2010-09-01

    Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR-binding fiber protein even while CAR protein and mRNA levels remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection.

  11. Spontaneous baryogenesis in warm inflation

    OpenAIRE

    Brandenberger, Robert H.; Yamaguchi, Masahide

    2003-01-01

    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  12. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    OpenAIRE

    Karina Faccio Mello; Adroaldo Lunardelli; Márcio Vinícius Fagundes Donadio; Eduardo Caberlon; Carmen Silvana Araújo de Oliveira; Carolina Maria Alves Bastos; Melissa Guerra Simões Pires; Fernanda Bordignon Nunes; Jarbas Rodrigues de Oliveira

    2011-01-01

    INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulate...

  13. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Klein, George, E-mail: Georg.Klein@ki.se [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden); Klein, Eva; Kashuba, Elena [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden)

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  14. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

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

    Directory of Open Access Journals (Sweden)

    Yao Wang

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

  16. SWAP-70 contributes to spontaneous transformation of mouse embryo fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yu-Tzu; Shu, Chung-Li; Lai, Jing-Yang; Lin, Ching-Yu; Chuu, Chih-Pin [Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC (China); Morishita, Kazuhiro; Ichikawa, Tomonaga [Division of Tumor and Cellular Biochemistry Department of Medical Sciences Faculty of Medicine University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-shi, Miyazaki 889-1692 Japan (Japan); Jessberger, Rolf [Faculty of Medicine Carl Gustav Carus, Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany); Fukui, Yasuhisa, E-mail: 990412@nhri.org.tw [Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC (China)

    2016-07-15

    Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, a putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs. - Highlights: • Mouse embryo fibroblasts (MEFs) lacking SWAP-70 do not cause spontaneous transform. • Adding back of SWAP-70 to SWAP-70-deficient MEFs induces spontaneous transformation. • SWAP-70 is required for spontaneous transformation of MEFs.

  17. Activation of human T lymphocytes by Leishmania lipophosphoglycan

    DEFF Research Database (Denmark)

    Kemp, M; Theander, T G; Handman, E

    1991-01-01

    This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon...... 63 failed to activate PBMC from any of the donors tested. These results show that the individuals cured from visceral leishmaniasis had expanded T-cell clones recognizing LPG, conceivably as a result of Leishmania infection. The LPG preparation was without detectable protein contamination. Thus...

  18. Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats.

    Science.gov (United States)

    Abe, Ikumi; Shirato, Ken; Hashizume, Yoko; Mitsuhashi, Ryosuke; Kobayashi, Ayumu; Shiono, Chikako; Sato, Shogo; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-01-01

    Folate (vitamin B(9)) plays key roles in cell growth and proliferation through regulating the synthesis and stabilization of DNA and RNA, and its deficiency leads to lymphocytopenia and granulocytopenia. However, precisely how folate deficiency affects the distribution of a variety of white blood cell subsets, including the minor population of basophils, and the cell specificity of the effects remain unclear. Therefore, we examined the effects of a folate-deficient diet on the circulating number of lymphocyte subsets [T-lymphocytes, B-lymphocytes, and natural killer (NK) cells] and granulocyte subsets (neutrophils, eosinophils, and basophils) in rats. Rats were divided into two groups, with one receiving the folate-deficient diet (FAD group) and the other a control diet (CON group). All rats were pair-fed for 8 weeks. Plasma folate level was dramatically lower in the FAD group than in the CON group, and the level of homocysteine in the plasma, a predictor of folate deficiency was significantly higher in the FAD group than in the CON group. The number of T-lymphocytes, B-lymphocytes, and NK cells was significantly lower in the FAD group than in the CON group by 0.73-, 0.49-, and 0.70-fold, respectively, indicating that B-lymphocytes are more sensitive to folate deficiency than the other lymphocyte subsets. As expected, the number of neutrophils and eosinophils was significantly lower in the FAD group than in the CON group. However, the number of basophils, the least common type of granulocyte, showed transiently an increasing tendency in the FAD group as compared with the CON group. These results suggest that folate deficiency induces lymphocytopenia and granulocytopenia in a cell-specific manner.

  19. Lymphocyte subpopulations in hypertrophied adenoid in children.

    Science.gov (United States)

    Musiatowicz, M; Wysocka, J; Kasprzycka, E; Hassmann, E

    2001-05-31

    Adenoid hypertophy is a common feature of childhood. It is currently accepted that it is caused by the antigen-stimulated increased activity of lymphocyte B (D. Bani, O. Gallo, O. Fini-Storchi, Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal and hypertrophic adenoids, Laryngoscope 10 (1994) 869-873). The adenoid decreases its size with age but the accompanying function alterations are not fully understood (L. Zawadzka-Glos, M. Chmielik, M. Wasik, Cell mediated response in hypertrophied tonsils in children, Nowa Pediatr. 4 (1997) 12-13). The understanding of the adenoid structure that undergoes some changes during the growth period is essential for evaluation of indications for adnoidectomy and assessment of its potential results. The aim of this study was to evaluate lymphocyte subpopulations in adenoid according to age. The analysed material was adenoids removed on the grounds of hypertrophy, which caused obstructive symptoms and/or otitis media with effusion onset. In the present study, we did not find any statistically significant differences among lymphocytes B, Th, and Ts subpopulations, respectively, in the adenoids of any of the age groups. We have found a statistically significant CD3(+) HLA-DR(+) cell percentage decrease in the group of children from 5 to 10 and above 10 years of age, respectively. We have also found a statistically significant increase in the percentage of NK (CD3(-) CD16(+) 56(+)) lymphocytes in relation to age. On the grounds of the current study, it may be stated that some changes in lymphocyte subpopulations in the adenoid take place with age.

  20. The mitogenic response of cryopreserved human lymphocytes in a microculture system.

    Science.gov (United States)

    Steel, C M; Ennis, M; Levin, A G; Wasunna, A

    1977-01-01

    Fresh blood lymphocytes from nine health donors have been compared with samples from the same donors, recovered after period of 2 to 21 months storage in liquid nitrogen, for the capacity to respond to a range of mitogens in vitro. A microculture assay was used, requireing aliquots of only 25,000 cells. The mean levels of 14C-thymidine uptake for fresh and frozen samples were closely comparable when the cells had been stimulated by PHA, Pokeweed or mitomycin-C-treated allogeneic lymphoblastoid cells. Lymphocytes from six East African donors, frozen by a very simple technique, were recovered after 3 or more years storage in liquid nitrogen. Five of the samples were in good condition as judged by cell viability and the capacity to form spontaneous 'E' rosettes with sheep erythrocytes. These five samples also responded extremely well to PHA, PWM and mitomycin-C-treated allogeneic lymphoblastoid cells using the microculture assay. This study extends the range of applications of cell banks in which small aliquots of blood lymphocytes are stored in liquid nitrogen for periods of several years.

  1. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

    Science.gov (United States)

    Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

    2016-07-01

    Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

  2. Primary lymphocytic lymphoma of lacrimal gland.

    Science.gov (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

    2017-02-01

    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Nuclear non proliferation and disarmament

    International Nuclear Information System (INIS)

    2000-01-01

    In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

  4. Effects of Electromagnetic Radiation from Smartphones on Learning Ability and Hippocampal Progenitor Cell Proliferation in Mice.

    Science.gov (United States)

    Choi, Yu-Jin; Choi, Yun-Sik

    2016-02-01

    Nonionizing radiation is emitted from electronic devices, such as smartphones. In this study, we intended to elucidate the effect of electromagnetic radiation from smartphones on spatial working memory and progenitor cell proliferation in the hippocampus. Both male and female mice were randomly separated into two groups (radiated and control) and the radiated group was exposed to electromagnetic radiation for 9 weeks and 11 weeks for male and female mice, respectively. Spatial working memory was examined with a Y maze, and proliferation of hippocampal progenitor cells were examined by 5-bromo-2'-deoxyuridine administration and immunohistochemical detection. When spatial working memory on a Y maze was examined in the 9(th) week, there was no significant difference in the spontaneous alternation score on the Y maze between the two groups. In addition, there was no significant difference in hippocampal progenitor cell proliferation. However, immunoreactivity to glial fibrillary acidic protein was increased in exposed animals. Next, to test the effect of recovery following chronic radiation exposure, the remaining female mice were further exposed to electromagnetic radiation for 2 more weeks (total 11 weeks), and spontaneous alternation was tested 4 weeks later. In this experiment, although there was no significant difference in the spontaneous alternation scores, the number of arm entry was significantly increased. These data indicate that although chronic electromagnetic radiation does not affect spatial working memory and hippocampal progenitor cell proliferation it can mediate astrocyte activation in the hippocampus and delayed hyperactivity-like behavior.

  5. Identification of two epitopes on the dengue 4 virus capsid protein recognized by a serotype-specific and a panel of serotype-cross-reactive human CD4+ cytotoxic T-lymphocyte clones.

    OpenAIRE

    Gagnon, S J; Zeng, W; Kurane, I; Ennis, F A

    1996-01-01

    We analyzed the CD4+ T-lymphocyte response of a donor who had received an experimental live-attenuated dengue 4 virus (D4V) vaccine. Bulk culture proliferative responses of peripheral blood mononuclear cells (PBMC) to noninfectious dengue virus (DV) antigens showed the highest proliferation to D4V antigen, with lesser, cross-reactive proliferation to D2V antigen. We established CD4+ cytotoxic T-lymphocyte clones (CTL) by stimulation with D4 antigen. Using recombinant baculovirus antigens, we ...

  6. Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma

    Directory of Open Access Journals (Sweden)

    Anza Khader

    2015-01-01

    Full Text Available Merkel cell carcinoma is an aggressive and frequently lethal tumor of the elderly, associated with sun exposure and immunosuppression which is less common in the dark-skinned. We report the case of a 40-year-old woman who presented with multiple slowly progressive, mildly itchy ulcerated plaques of size ranging from 2 × 3 cm to 5 × 7 cm on the left knee of 1 year duration. Skin biopsy showed diffuse dermal infiltration by small round cells with molding of cells and lymphocyte infiltration. The cells stained positive for cytokeratin (CK 20, CK7, neuron-specific enolase, and chromogranin. The skin lesions underwent spontaneous regression within 1 month of skin biopsy and have not recurred during the past 2 years. The immune mechanisms triggered by biopsy possibly explain the spontaneous regression.

  7. Morphological and dynamic MR evaluation of a giant spontaneous vertebrovertebral fistula during endovascular therapy

    International Nuclear Information System (INIS)

    McGlade, C.; Lufkin, R.; Vinuela, F.; Dion, J.; Lylyck, P.; Bentson, J.; Martin, N.

    1989-01-01

    A case of verbro-vertebral fistula in a patient with neurofibromatosis is presented with emphasis on magnetic resonance (MR) evaluation and integration with endovascular therapy. Vascular involvement is a known complication of neurofibromatosis ranging from intimal proliferation causing arterial narrowing, development of small aneurysms, to spontaneous fistulas probably secondary to mesodermal dysplasia. This case report illustrates the latter and portrays a role for MR in diagnosis and follow-up during therapeutic measures. (author). 14 refs.; 3 figs

  8. Spontaneous oscillations in microfluidic networks

    Science.gov (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

    2017-11-01

    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  9. General features of spontaneous baryogenesis

    Science.gov (United States)

    Arbuzova, Elena

    2017-04-01

    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  10. Spontaneous osteonecrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail: skattapuram@partners.org

    2008-07-15

    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  11. Requirement of mouse BCCIP for neural development and progenitor proliferation.

    Directory of Open Access Journals (Sweden)

    Yi-Yuan Huang

    Full Text Available Multiple DNA repair pathways are involved in the orderly development of neural systems at distinct stages. The homologous recombination (HR pathway is required to resolve stalled replication forks and critical for the proliferation of progenitor cells during neural development. BCCIP is a BRCA2 and CDKN1A interacting protein implicated in HR and inhibition of DNA replication stress. In this study, we determined the role of BCCIP in neural development using a conditional BCCIP knock-down mouse model. BCCIP deficiency impaired embryonic and postnatal neural development, causing severe ataxia, cerebral and cerebellar defects, and microcephaly. These development defects are associated with spontaneous DNA damage and subsequent cell death in the proliferative cell populations of the neural system during embryogenesis. With in vitro neural spheroid cultures, BCCIP deficiency impaired neural progenitor's self-renewal capability, and spontaneously activated p53. These data suggest that BCCIP and its anti-replication stress functions are essential for normal neural development by maintaining an orderly proliferation of neural progenitors.

  12. T lymphocytes subsets and cytokine pattern induced by vaccination against bovine brucellosis employing S19 calfhood vaccination and adult RB51 revaccination.

    Science.gov (United States)

    Dorneles, Elaine M S; Teixeira-Carvalho, Andréa; Araújo, Márcio S S; Lima, Graciela Kunrath; Martins-Filho, Olindo A; Sriranganathan, Nammalwar; Lage, Andrey P

    2014-10-21

    The aims of this study were to address the protective immune response induced by S19 vaccination (n=10) and RB51 revaccination, in pregnant (n=9) and non-pregnant (n=10) S19 calfhood-vaccinated cattle as follows: evaluate the in vitro CD4(+) and CD8(+) T-lymphocytes specific proliferation, and in vitro expression of IFN-γ by CD4(+) and CD8(+) T-cells and IL-4 by CD4(+), CD8(+) and CD21(+) lymphocytes subset. Upon in vitro stimulation with γ-irradiated Brucella abortus 2308, blood mononuclear cells from S19 vaccinated and RB51 revaccinated cows exhibited significantly higher proliferation of CD4(+) and CD8(+) T-lymphocytes and CD4(+)IFN-γ(+) T-cells compared to non-vaccinated animals. RB51 revaccination, regardless of the pregnancy status, did not enhance the proliferation of CD4(+) or CD8(+) T-cells nor IFN-γ or IL-4 production. Data from the present study suggest that cattle's cellular immune response induced after brucellosis vaccination and revaccination is due to CD4(+) and CD8(+) T-lymphocytes, being CD4(+) T-cells the main source of IFN-γ. Copyright © 2014. Published by Elsevier Ltd.

  13. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  14. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P

    1991-01-01

    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage was s...

  15. Genotoxic effects of borax on cultured lymphocytes.

    Science.gov (United States)

    Pongsavee, Malinee

    2009-03-01

    The effect of borax on human chromosomes was analyzed in this study. Venous blood from 30 male students at Thammasat University, Thailand (age 18-25 years) was collected for lymphocyte cell cultures. This experiment was divided into two groups: the first group was the control group and the second group was the experimental group. The lymphocyte cells in the control group were cultured without borax. The experimental group was divided into four subgroups. The lymphocyte cells in each experimental subgroup were cultured with different concentrations of borax (0.1 mg/ml, 0.15 mg/ml, 0.2 mg/ml and 0.3 mg/ml). Human chromosomes were studied for abnormalities through Giemsa-staining and G-banding. The results show that the numbers of metaphase plates (the metaphase plate which contained 46 chromosomes; 46, XY) and metaphase chromosomes were reduced when lymphocyte cells were cultured with 0.15 mg/ml (57.2%), 0.2 mg/ml (50.8%) and 0.3 mg/ml (42.3%) concentrations of borax. There was a statistically significant difference between the control and experimental subgroups (p borax concentration experimental subgroup. This shows that borax (at 0.15, 0.2 and 0.3 mg/ml concentrations) affects the cell and human chromosomes (both numerical and structural abnormalities). Borax may cause human chromosome abnormalities and lead to genetic defects.

  16. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds w...

  17. Lymphocyte adenylate cyclase activity in immunosuppressed patients

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.

    1989-01-01

    In order to determine whether alterations of adenylate cyclase are involved in the immunosuppressive effect of glucocorticoid/cyclosporin treatment we measured basal, prostaglandin E1-, and forskolin-stimulated cAMP production in lymphocyte membranes from kidney transplant patients undergoing

  18. Spondylarthritis in the absence of B lymphocytes

    NARCIS (Netherlands)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P.

    2008-01-01

    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

  19. [Enterobacterial antigen in human peripheral blood lymphocytes].

    Science.gov (United States)

    Faure-Fontenla, M A; García-Tamayo, F

    1989-11-01

    The following study has as prior history the research reports which have shown the existence of an antigenic tissue deposit in gram-negative enterobacteria. The antigens of the enterobacteria have also been found in the lymphocytic membranes and cytoplasm. Since intestinal lymphoid tissue cells can recirculate by means of the thoracic duct to the peripheral venous system, it was proposed that the circulating lymphocytes in healthy people could also contain small amounts of a common enterobacterial antigen. The study was carried out in 15 human venous blood samples, of which the lymphocytic population was separated to later be used in the preparation of 15 alcohol soluble extracts. This material was used for inhibiting the immuno-hemolysis assay in three occasions in order to show the presence of antigens shared by different enterobacterias, using as reference a fraction separated from the LPS of Escherichia coli 08. The results showed that the human lymphocytes also had antigenic determinants common to gram-negative bacteria.

  20. Lymphocyte dynamics in health and disease

    NARCIS (Netherlands)

    van Gent, R.

    2009-01-01

    Following immune depletion, it is vital that the immune system recovers rapidly to avoid severe or life-threatening infections. In adults, full recovery of CD4+ and CD8+ T-cell counts, important cell types of the immune system, may take years. Similar to other lymphocytes, T cells start their

  1. Immunohistochemical evaluation of lymphocyte populations in the ...

    African Journals Online (AJOL)

    Here we sought to quantify T and B lymphocyte populations in the lacrimal tissue of the nictitans glands of dogs with iKCS those with neurological KCS (nKCS)and also in dogs with tear production within the recognized normal levels and no ocular surface signs of KCS. Nictitans glands were obtained from 10 healthy dogs ...

  2. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  3. Neutrophil lymphocyte ratio predicts postoperative pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  4. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  5. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Lipopolysaccharide (LPS) is a predominant glycolipid in the outer membranes of gam-negative bacteria that stimulates monocytes, macrophages, and neutrophils to produce cytokines. The aim was to study the expression profile of TLRs and cytokines and determine the role of LPS in the peripheral blood lymphocytes.

  6. Sister Chromatid Exchanges (=SCEs) in Lymphocytes of persons working at Shlobin (USSR), 150km north of Chernobyl

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.

    1988-08-01

    SCEs are considered to be a sensitive indicator for the DNA damaging effects of mutagenic and carcinogenic agents. In 1986, during the Chernobyl accident, employees of an Austrian company worked at Shlobin, 150km north of Chernobyl. At their return to Austria blood as taken and spontaneously occurring and MMC induced SCEs were studied. Spontaneously occurring SCEs in lymphocytes of 'exposed' and 'unexposed' persons were only insignificantly different when results were summarized for all test persons. A significant influence of smoking could be established. When results were correlated with the time interval between the Chernobyl accident and the date of blood sampling, the increased rate of spontaneous SCEs observed soon after the accident decreased to the normal range during the following months. Irrespective of the molecular mechanism that might be the rationale for the observed decreased induction of SCEs in lymphocytes of exposed persons, the estimation of MMC induced SCEs proved to be the most sensitive test to demonstrate population exposure to low doses of ionizing radiation. 7 refs., 1 fig., 5 tabs. (Author)

  7. Clonally expanded T lymphocytes from atomic bomb survivors in vitro show no evidence of cytogenetic instability.

    Science.gov (United States)

    Hamasaki, K; Kusunoki, Y; Nakashima, E; Takahashi, N; Nakachi, K; Nakamura, N; Kodama, Y

    2009-08-01

    Abstract Genomic instability has been suggested as a mechanism by which exposure to ionizing radiation can lead to cancer in exposed humans. However, the data from human cells needed to support or refute this idea are limited. In our previous study on clonal lymphocyte populations carrying stable-type aberrations derived from A-bomb survivors, we found no increase in the frequency of sporadic additional aberrations among the clonal cell populations compared with the spontaneous frequency in vivo. That work has been extended by using multicolor FISH (mFISH) to quantify the various kinds of chromosome aberrations known to be indicative of genomic instability in cloned T lymphocytes after they were expanded in culture for 25 population doublings. The blood T cells used were obtained from each of two high-dose-exposed survivors (>1 Gy) and two control subjects, and a total of 66 clonal populations (36 from exposed and 30 from control individuals) were established. For each clone, 100 metaphases were examined. In the case of exposed lymphocytes, a total of 39 additional de novo stable, exchange-type aberrations [translocation (t) + derivative chromosome (der)] were found among 3600 cells (1.1%); the corresponding value in the control group was 0.6% (17/3000). Although the ratio (39/3600) obtained from the exposed cases was greater than that of the controls (17/3000), the difference was not statistically significant (P = 0.101). A similar lack of statistical difference was found for the total of all structural chromosome alterations including t, der, dicentrics, duplications, deletions and fragments (P = 0.142). Thus there was no clear evidence suggesting the presence of chromosome instabilities among the clonally expanded lymphocytes in vitro from A-bomb survivors.

  8. Ubiquitin specific protease 21 is dispensable for normal development, hematopoiesis and lymphocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Jaspreet Pannu

    Full Text Available USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.

  9. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Op...in Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  10. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.

    1982-01-01

    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  11. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

    Science.gov (United States)

    Fabbri, Giulia; Holmes, Antony B; Viganotti, Mara; Scuoppo, Claudio; Belver, Laura; Herranz, Daniel; Yan, Xiao-Jie; Kieso, Yasmine; Rossi, Davide; Gaidano, Gianluca; Chiorazzi, Nicholas; Ferrando, Adolfo A; Dalla-Favera, Riccardo

    2017-04-04

    Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival, and signal transduction. In particular, we show that NOTCH1 transactivates MYC via binding to B-cell-specific regulatory elements, thus implicating this oncogene in CLL development. These results significantly extend the role of NOTCH1 in CLL pathogenesis, and have direct implications for specific therapeutic targeting.

  12. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri

    2015-07-01

    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  13. Spontaneity of communication in individuals with autism.

    Science.gov (United States)

    Chiang, Hsu-Min; Carter, Mark

    2008-04-01

    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  14. Lessons in IBD Pathogenesis from New Animal Models of Spontaneous Colitis

    Directory of Open Access Journals (Sweden)

    R Balfour Sartor

    1995-01-01

    Full Text Available The recent explosion of transgenic and targeted gene deleted (knockout [KO] rodents has yielded a number of new animal models of spontaneous, chronic intestinal inflammation that have provided novel insights into the pathogenesis of human inflammatory bowel disease (IBD. Spontaneous colitis resulting from deletion of genes encoding key immunoregulatory cytokines (interleukin [IL]-2, IL-10 and transforming growth factor [TGF]-beta and T cell receptors (TCRs demonstrates that an intact mucosal immune response prevents colitis. The TCR KO model incriminates B lymphocytes in spontaneous colonic inflammation – TCR KO with intact B cells causes colitis, but simultaneous deletion of T and B cells does not. This model and induction of colitis in severe combined immunodeficient (SCID mice by constitution with one T cell subset (CD45RHhi, but prevention by addition of the CD45RBlo subset, strongly suggest that T cell subsets down-regulate inflammation in the normal, immunocompetent host. An essential role for normal luminal bacteria in induction and perpetuation of enterocolitis is provided by the absence of chronic intestinal inflammation in germ-free (sterile IL-2 KO mice and human leukocyte antigen (HLA-B27 transgenic rats, and attenuated inflammation in IL-2 and IL-10 KO mice raised under specific pathogen-free conditions. The fundamental role of host genetic susceptibility in chronic intestinal inflammation and systemic manifestations is established by development of spontaneous colitis and perianal inflammation in C3H/HeJ Bir substrain mice and HLA-B27 transgenic rats.

  15. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S

    2002-07-01

    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  16. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu

    2009-03-01

    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  17. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.

    2006-01-01

    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  18. Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Desch, P; Asslaber, D; Kern, D; Schnidar, H; Mangelberger, D; Alinger, B; Stoecher, M; Hofbauer, S W; Neureiter, D; Tinhofer, I; Aberger, F; Hartmann, T N; Greil, R

    2010-09-02

    The Hedgehog (Hh) pathway regulates cell proliferation and survival and contributes to tumorigenesis. We investigated the expression and function of this pathway in B-cell chronic lymphocytic leukemia (CLL) cells and in healthy B lymphocytes. Profiling of cognate Hh pathway members revealed reduced expression of two key Hh signaling effectors, Smoothened (SMOH) and GLI, in CLL cells, whereas transcription levels of other investigated members resembled normal B-lymphocyte levels. Examining the functional role of SMOH and GLI in cell survival, we found that CLL cells were hardly sensitive toward specific SMOH inhibition, but showed an unspecific decline in cell viability in response to high concentrations of the SMOH antagonist cyclopamine. In contrast, treatment with the novel GLI antagonist GANT61 reduced expression of the target gene Patched and preferentially decreased the viability of malignant cells. Specific RNA interference knockdown experiments in a CLL-derived cell line confirmed the autonomous role of GLI in malignant cell survival. GANT61-induced apoptosis in primary leukemic cells was partly attenuated by protective stromal cells, but not soluble sonic hedgehog ligand. In summary, our data show a downregulation of the classical Hh pathway in CLL and suggest an intrinsic SMOH-independent role of GLI in the ex vivo survival of CLL cells.

  19. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo.

    Science.gov (United States)

    Akesson, Ch; Pero, R W; Ivars, F

    2003-01-01

    Water extracts of the bark of Uncaria tomentosa, a vine indigenous to South America, has been used for generations as an "immuno modulator". To understand the basis of this immuno modulatory effect we fed mice in their drinking water with C-Med 100, which is a commercially available water extract from Uncaria tomentosa. We found a dose-dependent increase in spleen cell numbers in the supplemented mice, but the proportions of B cells, T cells, NK cells, granulocytes, and memory lymphocytes were normal. However, there were no detectable changes of the lymphoid architecture of the spleen even after long-term treatment. Further, when C-Med 100 treatment was interrupted the cellularity returned to normal level within four weeks. The increased number of lymphocytes was most likely not due to increased production because C-Med 100 did not have any significant effect on precursor cells nor on the accumulation of recent thymic emigrants in the spleen. We conclude that accumulation is most likely due to prolonged cell survival, because adoptive transfer experiments demonstrated that C-Med 100 treatment significantly prolonged lymphocyte survival in peripheral lymphoid organs, without increasing their proliferation rate. Since the accumulation was reversible and without detectable pathological effects, these results suggest the use of C-Med 100 as a potential agent for clinically accelerating the recovery of patients from leukopenia.

  20. L-carnitine mediates protection against DNA damage in lymphocytes of aged rats.

    Science.gov (United States)

    Thangasamy, Thilakavathy; Jeyakumar, Preethy; Sittadjody, Sivanandane; Joyee, Antony George; Chinnakannu, Panneerselvam

    2009-04-01

    It has been proposed that age-associated disorders are related to a time-dependent shift in the antioxidant/prooxidant balance towards oxidative damage. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which can in turn lead to oxidative injury. Carnitine is a vitamin-like compound that serves as a carrier to transport long-chain fatty acids into the mitochondria for beta-oxidation. In the present study, the effect of L-carnitine, a widely recognized essential nutrient, was evaluated on the status of lipid peroxidation and certain antioxidant enzymes and DNA damage in lymphocytes with relation to age in male wistar rats. The levels of lipid peroxides were remarkably increased whereas, the activities of antioxidant enzymes were significantly decreased in aged control animals when compared to younger controls. In aged animals, administration of L-carnitine for 21 days significantly decreased the levels of lipid peroxides and improved the activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. L-Carnitine enhanced T-cell proliferative responses as evaluated by T-cell proliferation assay using [3H] thymidine incorporation and also significantly reduced DNA damage, apoptosis and TNF-alpha level in lymphocytes of aged animals. Our results suggest that L -carnitine may have a vital role in improving functions in the cells of the immune system particularly the lymphocytes possibly through its antioxidant action.

  1. Inorganic tin compounds do not induce micronuclei in human lymphocytes in the absence of metabolic activation.

    Science.gov (United States)

    Damati, Artemis; Vlastos, Dimitris; Philippopoulos, Athanassios I; Matthopoulos, Demetrios P

    2014-04-01

    The genotoxic evaluation (in vitro analysis) of a series of eight inorganic tin(II) and tin(IV) compounds [tin(II) acetate, tin(II) chloride, tin(II) ethylhexanoate, tin(II) oxalate, tin(II) oxide, tin(IV) acetate, tin(IV) chloride and tin(IV) oxide], for the detection of micronuclei in human blood lymphocytes, was performed in the absence of metabolic activation by the cytokinesis-block micronucleus assay. Human lymphocytes were treated for over one cell cycle (31 hours), with concentrations ranging from 1 to 75 μM (1, 5, 10, 20, 50 and 75 μM), of tin(II) and tin(IV) salts dissolved in dimethyl sulfoxide. The above-listed concentrations cover the values that have been detected in humans with no occupational exposure to tin compounds. The experimental results show the absence of genotoxicity for all inorganic compounds tested in the specific concentrations and experimental conditions. Cytotoxic effects of tin(II) and tin(IV) compounds were evaluated by the determination of cytokinesis block proliferation index and cytotoxicity percentage. Our observations on the cytotoxicity pattern of the tested tin(II) and tin(IV) compounds indicate that they are cytotoxic in several tested concentrations to human lymphocytes treated in vitro. The observed differences in cytotoxicity of each tested compound might reflect differences in their chemical structure.

  2. The immunometabolite S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate

    Science.gov (United States)

    Tyrakis, Petros A.; Palazon, Asis; Macias, David; Lee, Kian. L.; Phan, Anthony. T.; Veliça, Pedro; You, Jia; Chia, Grace S.; Sim, Jingwei; Doedens, Andrew; Abelanet, Alice; Evans, Colin E.; Griffiths, John R.; Poellinger, Lorenz; Goldrath, Ananda. W.; Johnson, Randall S.

    2016-01-01

    R-2-hydroxyglutarate accumulates to millimolar levels in cancers with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both R- and S-2-hydroxyglutarate, the other enantiomer of this metabolite, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that CD8+ T-lymphocytes accumulate 2-hydroxyglutarate in response to T-cell receptor triggering. This increases to millimolar levels in physiological oxygen conditions, via a hypoxia inducible factor 1 alpha-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8+ T-lymphocyte differentiation in response to this metabolite. Modulation of histone and DNA demethylation as well as hypoxia inducible factor 1 alpha stability mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8+ T-lymphocytes. Thus S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, via a metabolic-epigenetic axis, to immune fate and function. PMID:27798602

  3. Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells

    Science.gov (United States)

    Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

    2015-01-01

    B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process. PMID:26265439

  4. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  5. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    International Nuclear Information System (INIS)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of 3 H-thymidine-labeled infiltrating cells ( 3 H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the 3 H-index is moderately elevated in stage I and high in stage III. The 3 H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the 3 H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas. (orig.) [de

  6. Immune Modulation in Normal Human Peripheral Blood Mononuclear Cells (PBMCs) (Lymphocytes) in Response to Benzofuran-2-Carboxylic Acid Derivative KMEG during Spaceflight

    Science.gov (United States)

    Okoro, Elvis; Mann, Vivek; Ellis, Ivory; Mansoor, Elvedina; Olamigoke, Loretta; Marriott, Karla Sue; Denkins, Pamela; Williams, Willie; Sundaresan, Alamelu

    2017-08-01

    Microgravity and radiation exposure during space flight have been widely reported to induce the suppression of normal immune system function, and increase the risk of cancer development in humans. These findings pose a serious risk to manned space missions. Interestingly, recent studies have shown that benzofuran-2-carboxylic acid derivatives can inhibit the progression of some of these devastating effects on earth and in modeled microgravity. However, these studies had not assessed the impacts of benzofuran-2- carboxylic acid and its derivatives on global gene expression under spaceflight conditions. In this study, the ability of a specific benzofuran-2-carboxylic acid derivative (KMEG) to confer protection from radiation and restore normal immune function was investigated following exposure to space flight conditions on the ISS. Normal human peripheral blood mononuclear cells (lymphocytes) treated with 10 µ g/ml of KMEG together with untreated control samples were flown on Nanoracks hardware on Spacex-3 flight. The Samples were returned one month later and gene expression was analyzed. A 1g-ground control experiment was performed in parallel at the Kennedy spaceflight center. The first overall subtractive unrestricted analysis revealed 78 genes, which were differentially expressed in space flight KMEG, untreated lymphocytes as compared to the corresponding ground controls. However, in KMEG-treated space flight lymphocytes, there was an increased expression of a group of genes that mediate increased transcription, translation and innate immune system mediating functions of lymphocytes as compared to KMEG-untreated samples. Analysis of genes related to T cell proliferation in spaceflight KMEG-treated lymphocytes compared to 1g-ground KMEG- treated lymphocytes revealed six T cell proliferation and signaling genes to be significantly upregulated (p role in promoting the proliferation of T-lymphocytes, the regulation of membrane trafficking, promote early response

  7. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

    Science.gov (United States)

    Parrish-Novak, J; Dillon, S R; Nelson, A; Hammond, A; Sprecher, C; Gross, J A; Johnston, J; Madden, K; Xu, W; West, J; Schrader, S; Burkhead, S; Heipel, M; Brandt, C; Kuijper, J L; Kramer, J; Conklin, D; Presnell, S R; Berry, J; Shiota, F; Bort, S; Hambly, K; Mudri, S; Clegg, C; Moore, M; Grant, F J; Lofton-Day, C; Gilbert, T; Rayond, F; Ching, A; Yao, L; Smith, D; Webster, P; Whitmore, T; Maurer, M; Kaushansky, K; Holly, R D; Foster, D

    2000-11-02

    Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

  8. Future non-proliferation challenges

    International Nuclear Information System (INIS)

    Yelchenko, Volodymyr

    2008-01-01

    Having chaired the Second Session of the Preparatory Committee Mr. Volodymyr Yelchenko noted that the NPT States parties reaffirmed the important role of the Treaty as the cornerstone of the global non-proliferation regime. They stressed that non-compliance with the Treaty provisions by States parties undermined non-proliferation and placed emphasis on the mutually reinforcing nature of disarmament and non-proliferation, and due respect for the right of States parties to the peaceful use of nuclear energy in conformity with the treaty. They reaffirmed the importance of promoting the peaceful uses of nuclear energy and international nuclear cooperation for peaceful purposes in ways consistent with the non-proliferation goal of the Treaty. The universality aspect was brought to the front with the lack of progress in this area. States parties called upon India, Israel and Pakistan to accede to the Treaty as non-nuclear-weapons states, promptly and without conditions and to bring into force comprehensive safeguards agreements, together with Additional Protocols, for ensuring non-proliferation. There is concern that non-States actors could gain access to weapons of mass destruction. One of the underlying themes at the Second Prepcom was the total elimination of nuclear weapons as the only absolute guarantee against their proliferation. Negative consequences to nuclear non-proliferation were also mentioned in the context of the abrogation of the Anti-Ballistic Missile Treaty and the development of missile defense systems, with the risk of a new arms race on Earth and in outer space. The importance of the immediate commencement of negotiations in the Conference of Disarmament on a treaty concerning fissile material for nuclear weapons or other nuclear explosive devices and the urgent conclusion of such a treaty as a beneficial step towards non-proliferation was stressed. The NPT states parties reaffirmed the role of the IAEA as the sole competent authority responsible for

  9. Mitogen-induced responses in lymphocytes from platypus, the Tasmanian devil and the eastern barred bandicoot.

    Science.gov (United States)

    Stewart, N J; Bettiol, S S; Kreiss, A; Fox, N; Woods, G M

    2008-10-01

    As the platypus (Ornithorhynchus anatinus), the Tasmanian devil (Sarcophilus harrisi) and the eastern barred bandicoot (Perameles gunni) are currently at risk of serious population decline or extinction from fatal diseases in Tasmania, the goal of the present study was to describe the normal immune response of these species to challenge using the lymphocyte proliferation assay, to give a solid basis for further studies. For this preliminary study, we performed lymphocyte proliferation assays on peripheral blood mononuclear cells (PBMC) from the three species. We used the common mitogens phytohaemagglutinin (PHA), concanavalin A (ConA), lipopolysaccharide (LPS) and pokeweed mitogen (PWM). All three species recorded the highest stimulation index (SI) with the T-cell mitogens PHA and ConA. Tasmanian devils and bandicoots had greater responses than platypuses, although variability between individual animals was high. For the first time, we report the normal cellular response of the platypus, the Tasmanian devil and the eastern barred bandicoot to a range of commonly used mitogens.

  10. Clonal expansion under the microscope: studying lymphocyte activation and differentiation using live-cell imaging.

    Science.gov (United States)

    Polonsky, Michal; Chain, Benjamin; Friedman, Nir

    2016-03-01

    Clonal expansion of lymphocytes is a hallmark of vertebrate adaptive immunity. A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and acquire various effector and memory phenotypes, which promote effective immune responses. Recent studies establish a large degree of heterogeneity in the level of expansion and in cell state between and within expanding clones. Studying these processes in vivo, while providing insightful information on the level of heterogeneity, is challenging due to the complex microenvironment and the inability to continuously track individual cells over extended periods of time. Live cell imaging of ex vivo cultures within micro fabricated arrays provides an attractive methodology for studying clonal expansion. These experiments facilitate continuous acquisition of a large number of parameters on cell number, proliferation, death and differentiation state, with single-cell resolution on thousands of expanding clones that grow within controlled environments. Such data can reveal stochastic and instructive mechanisms that contribute to observed heterogeneity and elucidate the sequential order of differentiation events. Intercellular interactions can also be studied within these arrays by following responses of a controlled number of interacting cells, all trapped within the same microwell. Here we describe implementations of live-cell imaging within microwell arrays for studies of lymphocyte clonal expansion, portray insights already gained from these experiments and outline directions for future research. These tools, together with in vivo experiments tracking single-cell responses, will expand our understanding of adaptive immunity and the ways by which it can be manipulated.

  11. 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.

  12. Time-course Interactions between Cell Proliferation and DNA Sequence Variants in a Mouse Model of Latent Carcinogenicity

    Science.gov (United States)

    A fundamental principle of non-mutagenic chemical carcinogenesis is that increased cell proliferation enhances spontaneous DNA damage. Over time, this damage drives mutations in oncogenic genes that ultimately lead to cancer. This concept is a central part of cancer mode of actio...

  13. Heterogeneous effects of histamine on proliferation of lung- and blood-derived T-cell clones from healthy and asthmatic persons

    NARCIS (Netherlands)

    Hol, B. E.; Krouwels, F. H.; Bruinier, B.; Lutter, R.; Bast, A.; Wierenga, E. A.; Jansen, H. M.; Out, T. A.

    1993-01-01

    We have studied the effects of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment

  14. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  15. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  16. Recurrent spontaneous attacks of dizziness.

    Science.gov (United States)

    Lempert, Thomas

    2012-10-01

    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  17. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Exacerbation of experimental autoimmune encephalomyelitis in P2X7R-/- mice: evidence for loss of apoptotic activity in lymphocytes.

    Science.gov (United States)

    Chen, Lanfen; Brosnan, Celia F

    2006-03-01

    The purinergic receptor P2X7R is a nucleotide-gated ion channel that has been proposed to function as a major regulator of inflammation. In this study we examined the role of this receptor in regulating inflammation in the CNS by determining the effects of the loss of this receptor (P2X7R-/-) on experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We show here that P2X7R-/- mice developed more severe clinical and pathological expression of EAE than wild type (WT) controls and that spleen and lymph node cells from P2X7R-/- mice proliferated more vigorously to Ag in vitro. Bone marrow (BM) radiation chimeras revealed that enhanced susceptibility to EAE was detected in chimeric mice of WT host engrafted with P2X7R-/- BM cells, indicating that the genotype of the BM cells regulated disease susceptibility. Coculture of P2X7R-/- macrophages with WT lymphocytes and vice versa showed that enhanced proliferative activity resided within the P2X7R-/- lymphocyte population and correlated with reduced levels of IFN-gamma and NO and apoptosis of lymphocytes. mRNA and protein for IFN-gamma were also significantly reduced in the CNS of P2X7R-/- mice with EAE. FACS analysis of cells isolated from the CNS showed significantly fewer annexin V/propidium iodide-positive lymphocytes in the CNS of P2X7R-/- mice early in the disease, and TUNEL staining of inflamed CNS tissues supported this result. From these data we conclude that enhanced susceptibility of P2X7R-/- mice to EAE reflects a loss of apoptotic activity in lymphocytes, supporting an important role for this receptor in lymphocyte homeostasis.

  19. Inhibition of DNA repair by whole body irradiation induced nitric oxide leads to higher radiation sensitivity in lymphocytes

    International Nuclear Information System (INIS)

    Sharma, Deepak; Santosh Kumar, S.; Raghu, Rashmi; Maurya, D.K.; Sainis, K.B.

    2007-01-01

    Full text: It is well accepted that the sensitivity of mammalian cells is better following whole body irradiation (WBI) as compared to that following in vitro irradiation. However, the underlying mechanisms are not well understood. Following WBI, the lipid peroxidation and cell death were significantly higher in lymphocytes as compared to that in vitro irradiated lymphocytes. Further, WBI treatment of tumor bearing mice resulted in a significantly higher inhibition of EL-4 cell proliferation as compared to in vitro irradiation of EL-4 cells. The DNA repair was significantly slower in lymphocytes obtained from WBI treated mice as compared to that in the cells exposed to same dose of radiation in vitro. Generation of nitric oxide following irradiation and also its role in inhibition of DNA repair have been reported, hence, its levels were estimated under both WBI and in vitro irradiation conditions. Nitric oxide levels were significantly elevated in the plasma of WBI treated mice but not in the supernatant of in vitro irradiated cells. Addition of sodium nitroprusside (SNP), a nitric oxide donor to in vitro irradiated cells inhibited the repair of DNA damage and sensitized cells to undergo cell death. It also enhanced the radiation-induced functional impairment of lymphocytes as evinced from suppression of mitogen-induced IL-2, IFN-γ and bcl-2 mRNA expression. Administration of N G -nitro-L-arginine-methyl-ester(L-NAME), a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. Our results indicated that nitric oxide plays a role in the higher radiosensitivity of lymphocytes in vivo by inhibiting repair of DNA damage

  20. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Nuclear proliferation and safeguards. Summary

    International Nuclear Information System (INIS)

    1982-03-01

    This comprehensive analysis of the technological, economic, and political factors affecting the potential spread of nuclear weapons proved useful in the congressional debate which culminated in the Nuclear Non-Proliferation Act of 1978. The report was subsequently published commercially and has been a frequently cited reference in the literature on proliferation and nuclear power. Despite developments since 1977, the information in the OTA report is still useful to those wishing to obtain an indepth understanding of the issues. Included is an analysis of why a nation might want nuclear weapons development program and the various sources of nuclear material are discussed. The control of proliferation is considered as well as its relation to the nuclear industry

  2. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    International Nuclear Information System (INIS)

    Ren, Zhenhua; Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin; Chen, Zhiguo; Zhang, Y. Alex

    2011-01-01

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: ► Spontaneous transformation of cynomolgus monkey MSCs in vitro. ► Transformed mesenchymal cells lack multipotency. ► Transformed mesenchymal cells are highly tumorigenic. ► Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  3. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Department of Anatomy, Anhui Medical University, Hefei, 230032 (China); Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Chen, Zhiguo, E-mail: chenzhiguo@gmail.com [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Stanford Institute for Stem Cell Biology and Regenerative Medicine and Department of Neurosurgery, Stanford, CA (United States); Zhang, Y. Alex, E-mail: yaz@bjsap.org [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China)

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  4. Lymphocytic subsets and low-dose exposure

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Eybl, E.

    1993-03-01

    The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

  5. Characteristics of T lymphocyte subpopulations 

    Directory of Open Access Journals (Sweden)

    Paulina Niedźwiedzka-Rystwej

    2013-05-01

    Full Text Available The paper describes the characteristics, receptor profile and functions of T lymphocyte subpopulations (helper, cytotoxic, regulatory, memory and others. Among T helper cells one can enumerate Th0, Th1, Th2, Th9, Th17, Th22, TFH and nTh2, while T cytotoxic cells include Tc, NKT, Tγδ, and T CD8αα (IEL. Among regulatory cells there are nTreg, iTreg, TR1, and iTR35, as well as T lymphocytes with CD8, such as CD8 CD122 , CD8 CD28-, and CD11c CD8 . And among memory T cells there are Tcm and Tem. Moreover, there are some so-called other T cells, such as Tn (T αβ CD4 and T αβ CD8 , T exhausted and T anergic. 

  6. The influences of age on T lymphocyte subsets in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Jing Xie

    2017-01-01

    Full Text Available The aim of this study is to evaluate the age related changes of T lymphocyte subsets in C57BL/6 mice and immune function. Multi-color immunofluorescence techniques that were used to analyse relative numbers of T lymphocyte subsets include CD4+, CD8+, naive and memory CD4+ and CD8+, CD8+CD28+ T cells in peripheral blood of C57BL/6 mice from different age groups (Group I: 2 months old; Group II: 7 months old; Group III: 21 months old; Splenocytes isolated from different group mice were stimulated with Con A to evaluate the proliferative ability. Compared with group I, group II had a significant reduction in the percentage of CD4+, naive CD4+ and CD8+ T cells and an increase in the percentage of CD8+ T cells, while group III had a significant reduction in the percentage of CD4+, naive CD4+ and CD8+ T cells and increase in the percentage of CD8+, memory CD4+ and CD8+ T cells in peripheral blood. Compared with group II, group III had a significant reduction in the percentage of naive CD8+ T cells and increase in the percentage of memory CD4+ and CD8+, CD8+CD28+ T cells in peripheral blood. The T lymphocyte proliferation in vitro showed that groups II and III had a lower proliferative capacity than group I, between groups II and III, there was not a significant difference. We provide relative values for the T lymphocyte subsets in the different age groups of C57BL/6 mice. The immune system began aging at 7 months old in C57BL/6 mice under a specific pathogen free environment.

  7. Ultracentrifuge and non-proliferation

    International Nuclear Information System (INIS)

    Voortman, A.J.

    1977-01-01

    The author states that there is no meaningful difference, from the point of view of proliferation between peaceful, civil, scientific application of nuclear fission, and the use of it in nuclear weapons. The proliferation of the nuclear technology for weapons appeared and appears to be closely connected with the spread of peaceful applications of nuclear technology. In connection with this, he discusses the Ultracentrifuge plant at Almelo (Netherlands) and the supply of nuclear technology by West-Germany especially to Brazil. Further the changed American policy and the possibility of an American/Russian deal to prevent the spread of the nuclear enrichment technology is discussed

  8. Mercury toxicity in beluga whale lymphocytes: Limited effects of selenium protection

    Energy Technology Data Exchange (ETDEWEB)

    Frouin, H. [Fisheries and Oceans Canada, Institute of Ocean Sciences, 9860 West Saanich Rd, P.O. Box 6000, Sidney, BC, V8L 4B2 (Canada); Loseto, L.L.; Stern, G.A. [Fisheries and Oceans Canada, Freshwater Institute, 501 University Crescent, Winnipeg, MB, R3T 2N6 (Canada); Haulena, M. [Vancouver Aquarium, 845 Avison Way, Vancouver, BC, V6G 3E2 (Canada); Ross, P.S., E-mail: peter.s.ross@dfo-mpo.gc.ca [Fisheries and Oceans Canada, Institute of Ocean Sciences, 9860 West Saanich Rd, P.O. Box 6000, Sidney, BC, V8L 4B2 (Canada)

    2012-03-15

    Increasing emissions of anthropogenic mercury represents a growing concern to the health of high trophic level marine mammals. In its organic form, this metal bioaccumulates, and can be toxic to several physiological endpoints, including the immune system. In this study, we (1) evaluated the effects of inorganic mercury (mercuric chloride, HgCl{sub 2}) and organic mercury (methylmercuric chloride, MeHgCl) on the in vitro function of lymphocytes isolated from the peripheral blood of beluga whales (Delphinapterus leucas); (2) characterized the potential protective effects of sodium selenite (Na{sub 2}SeO{sub 3}) on cell proliferation of HgCl{sub 2} or MeHgCl-treated beluga whale lymphocytes; and (3) compared these dose-dependent effects to measurements of blood Hg in samples collected from traditionally harvested beluga whales in the western Canadian Arctic. Lymphocyte proliferative responses were reduced following exposure to 1 {mu}M of HgCl{sub 2} and 0.33 {mu}M of MeHgCl. Decreased intracellular thiol levels were observed at 10 {mu}M of HgCl{sub 2} and 0.33 {mu}M of MeHgCl. Metallothionein induction was noted at 0.33 {mu}M of MeHgCl. Concurrent exposure of Se provided a degree of protection against the highest concentrations of inorganic Hg (3.33 and 10 {mu}M) or organic Hg (10 {mu}M) for T-lymphocytes. This in vitro protection of Se against Hg toxicity to lymphocytes may contribute to the in vivo protection in beluga whales exposed to high Hg concentrations. Current Hg levels in free-ranging beluga whales from the Arctic fall into the range of exposures which elicited effects on lymphocytes in our study, highlighting the potential for effects on host resistance to disease. The implications of a changing Arctic climate on Hg fate in beluga food webs and the consequences for the health of beluga whales remain pressing research needs.

  9. In vitro temperature dependent activation of T-lymphocytes in Common wall lizards (Podarcis muralis in response to PHA stimulation

    Directory of Open Access Journals (Sweden)

    Roberto Sacchi

    2014-12-01

    Full Text Available Ecological immunology attempts to explain the variability of immune response among individuals by invoking costs and trade-offs, which may optimize the immune defence against pathogens. In ectotherms body temperature is correlated to that of the surrounding environment, so that their entire physiology, including immune functions, is influenced by the environmental temperature. We used in vitro phytohaemoagglutinin (PHA stimulation in order to assess the effects of temperature on cell mediated adaptive response in male and female Common wall lizards (Podarcis muralis. Cell cultures were prepared from blood samples, inoculated with PHA and incubated at 22°C, 25°C, 32°C, and 38°C for three days. PHA stimulation caused proliferation of T-lymphocytes, but the effect depended on the incubation temperature. Lymphocyte proliferation was significantly impaired at both 22°C and 38°C compared to 32°C, which represented the highest levels of activation. Furthermore, lymphocyte activation was more variable in males while females were less immune suppressed than males at low temperatures. Differences between sexes suggest a possible influence of steroid hormones.

  10. Value of large scale expansion of tumor infiltrating lymphocytes in a compartmentalised gas-permeable bag: interests for adoptive immunotherapy

    Science.gov (United States)

    2011-01-01

    Background Adoptive cell therapy (ACT) has emerged as an effective treatment for patients with metastatic melanoma. However, there are several logistical and safety concerns associated with large-scale ex vivo expansion of tumour-specific T lymphocytes for widespread availability of ACT for cancer patients. To address these problems we developed a specific compartmentalised bag allowing efficient expansion of tumour-specific T lymphocytes in an easy handling, closed system. Methods Starting from lymph nodes from eight melanoma patients, we performed a side-by-side comparison of Tumour-Infiltrating Lymphocytes (TIL) produced after expansion in the compartmentalised bag versus TIL produced using the standard process in plates. Proliferation yield, viability, phenotype and IFNγ secretion were comparatively studied. Results We found no differences in proliferation yield and cell viability between both TIL production systems. Moreover, each of the cell products complied with our defined release criteria before being administered to the patient. The phenotype analysis indicated that the compartmentalised bag favours the expansion of CD8+ cells. Finally, we found that TIL stimulated in bags were enriched in reactive CD8+ T cells when co-cultured with the autologous melanoma cell line. Conclusions The stimulation of TIL with feeder cells in the specifically designed compartmentalised bag can advantageously replace the conventional protocol using plates. In particular, the higher expansion rate of reactive CD8+ T cells could have a significant impact for ACT. PMID:21575188

  11. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien

    2014-01-01

    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  12. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  13. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  14. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)

    2002-11-01

    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  15. Spontaneity and Equilibrium II: Multireaction Systems

    Science.gov (United States)

    Raff, Lionel M.

    2014-01-01

    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  16. Radiosensitivity of human lymphocytes and thymocytes

    International Nuclear Information System (INIS)

    Kwan, D.K.; Norman, A.

    1977-01-01

    The in vitro survival of human peripheral blood lymphocytes and thymocytes was measured 4 days following graded doses of γ radiation. Results indicate considerable heterogeneity among lymphocyte subpopulations with respect to radiosensitivity. Total T lymphocytes were characterized by rosette formation with neuraminidase-treated sheep red blood cells (nSRBC); early T (T/sub E/) cells, by early rosettes; and B cells, by their inability to form nSRBC rosettes. Late T (T/sub L/) cells were defined as T -- T/sub E/. Survival curves of T, T/sub E/, and B cells are biphasic. The radiosensitive and radioresistant components of T, T/sub E/, and B cells all have a D 0 of about 50 and 550 rad, respectively. B cells appeared to be slightly more radiosensitive than T cells. T/sub L/ cells and thymocytes, however, appeared to be homogeneous with respect to radiosensitivity, both having D 0 values of about 135 rad. The survival of T cells in mixed T and B cell cultures resembled that of separated T cells, suggesting that ionizing radiation has no significant effect on rosette formation. It also indicates that interactions of T and B cells do not significantly affect their radiation responses

  17. Decreased lymphocyte dopamine transporter in romantic lovers.

    Science.gov (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana

    2017-06-01

    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  18. 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.

  19. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth

    2016-01-01

    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  20. Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: a possible manifestation of immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Kuwahara, Hiroya; Tsuchiya, Kuniaki; Kobayashi, Zen; Inaba, Akira; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2014-02-01

    Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome. © 2013 Japanese Society of Neuropathology.

  1. Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation.

    Directory of Open Access Journals (Sweden)

    Jacek M Witkowski

    2008-01-01

    Full Text Available Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+ cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.

  2. Comparing seven mitogens with PHA-M for improved lymphocyte stimulation in dicentric chromosome analysis for bio-dosimetry

    International Nuclear Information System (INIS)

    Beinke, C.; Port, M.; Lamkowski, A.; Abend, M.

    2016-01-01

    Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose estimation. Two limiting factors of DCA are the time-consuming lymphocyte stimulation and proliferation using the lectin PHA-M and the upper dose limit of individual dose assessment of ∼4 Gy. By measuring the mitotic index (MI), the authors investigated systematically whether the stimulation of lymphocytes can be improved after administration of alternative (and combined) mitogens. The authors compared the lymphocyte stimulation effectiveness of the traditionally used PHA-M (from Phaseolus vulgaris) with seven cited mitogens by determination of MIs: five lectins namely CNA (concanavalin A), PW (pokeweed), LMA (Maackia amurensis), LTV (T. vulgaris), PHA-L (P. vulgaris) as well as LPS (lipopolysaccharide, Escherichia coli) and SLO (strepto-lysine O, Streptococcus pyogenes) were applied. The conventional protocol using PHA-M for lymphocyte stimulation proved to be superior over lower/higher PHA-M concentrations as well as seven other mitogens administered either alone or combined with SLO or LPS. (authors)

  3. The (perceived) meaning of spontaneous thoughts.

    Science.gov (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  4. Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation.

    Science.gov (United States)

    Belot, Marie-Pierre; Abdennebi-Najar, Latifa; Gaudin, Françoise; Emilie, Dominique; Machelon, Véronique

    2007-12-01

    Mast cells proliferate in vivo in areas of active fibrosis, during parasite infestations, in response to repeated immediate hypersensitivity reactions and in patients with mastocytosis. We investigated how progesterone reduces the proliferation of HMC-1(560) mast cells that proliferate spontaneously in culture. Cells were incubated with 1 microM to 1 nM progesterone for 24-48 h. Progesterone (1 microM) reduced the spontaneous proliferation of HMC-1(560) mast cells to half that of cells cultured without hormone. [(3)H] thymidine incorporation was only 50% of control; there were fewer cells in G2/M and more cells in G0/G1. The amounts of phospho-Raf-1 (Tyr 340-341) and phospho-p42/p44 MAPK proteins were also reduced. In contrast progesterone had no effect on MAP kinase-phosphatase-1. The Raf/MAPK pathway, which depends on Src kinase activity, is implicated in the control of cell proliferation. HMC-1(560) cells incubated with the tyrosine kinase inhibitor PP1 proliferated more slowly than controls and had less phospho-Raf-1 (Tyr 340-341) and phospho-p42/p44 MAPK. The Csk homologous kinase (CHK), an endogenous inhibitor of Src protein tyrosine kinases, was also enhanced in progesterone-treated cells. In contrast, progesterone had no effect on the growth of cells transfected with siRNA CHK. We conclude that progesterone increases the amount of csk homologous kinase, which in turn reduces HMC-1(560) mast cell proliferation. This effect parallels decreases in the phosphorylated forms of Raf-1 and p42/44 MAPK, as their production depends on Src kinase activity. (c) 2007 Wiley-Liss, Inc.

  5. Nuclear Proliferation Technology Trends Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  6. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai

    2015-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  7. Lack of common TCRA and TCRB clonotypes in CD8+/ TCRαβ+ T-cell large granular lymphocyte leukemia: A review on the role of antigenic selection in the immunopathogenesis of CD8+ T-LGL

    NARCIS (Netherlands)

    Y. Sandberg (Yorick); M.J. Kallemeijn (Martine); W.A. Dik (Willem); D. Tielemans; I.L.M. Wolvers-Tettero (I. L M); E.J. van Gastel-Mol (Ellen); T. Szczepanski (Tomasz); Y. Pol (Y.); N. Darzentas (Nikos); J.J.M. van Dongen (Jacques); A.W. Langerak (Anton)

    2014-01-01

    textabstractClonal CD8 +/T-cell receptor (TCR)αβ+ T-cell large granular lymphocyte (T-LGL) proliferations constitute the most common subtype of T-LGL leukemia. Although the etiology of T-LGL leukemia is largely unknown, it has been hypothesized that chronic antigenic stimulation contributes to the

  8. Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression.

    Science.gov (United States)

    Lutz, C; Mozaffari, M; Tosevski, V; Caj, M; Cippà, P; McRae, B L; Graff, C L; Rogler, G; Fried, M; Hausmann, M

    2015-08-01

    Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) , CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer's patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-) (/) (-) and Il10(-) (/) (-) × Bim(-) (/) (-) impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD. © 2015 British Society for Immunology.

  9. Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

    Science.gov (United States)

    Häyry, P.; Defendi, V.

    1970-01-01

    We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

  10. Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production

    Science.gov (United States)

    Jeelall, Yogesh S.; Wang, James Q.; Law, Hsei-Di; Domaschenz, Heather; Fung, Herman K.H.; Kallies, Axel; Nutt, Stephen L.

    2012-01-01

    Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewiring of the signaling apparatus or if it can arise from a single molecular change. By introducing individual CARD11 mutations found in human lymphomas into antigen-activated mature B lymphocytes in mice, we find here that lymphoma-derived CARD11 mutations switch the effect of self-antigen from inducing B cell death into T cell–independent proliferation, Blimp1-mediated plasmablast differentiation, and autoantibody secretion. Our findings demonstrate that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells and that mutations in this switch represent a powerful initiator for aberrant B cell responses in vivo. PMID:23027925

  11. HOMEOSTATC PROLIFERATION AS A BASIS FOR THE INEVITABLE FORMATION OF TOTAL IMMUNODEFICIENCY

    Directory of Open Access Journals (Sweden)

    V. A. Kozlov

    2014-01-01

    Full Text Available Numerous literature data indicate to gradual, but steady ageependent decrease of immunological reactivity in human organism, manifesting as a reduced ability to develop specific immune response, both of cellular and humoral type. Such negative trends result into increased proposition and frequency of various diseases, including cancer and autoimmune disorders. Finally, an age-associated immunodeficiency is developed even in normal organism, without clear background of specific disorders. The multicomponent mechanisms of such deficiency are not yet fully clarified. One may assume that, among these potentially leading mechanisms, a homeostatic proliferation may be of sufficient importance. This type of cell growth is shown to accompany any negative effects on the numbers of lymphocytes in the body. It manifests as a reduced ability of lymphocytes to recognize foreign antigens associated with a background increase of self-reactive cells.

  12. Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal Sac: A Case Series.

    Science.gov (United States)

    Krishna, Yamini; Irion, Luciane D; Karim, Sozan; Dharmsena, Aruna; McCormick, Austin; Coupland, Sarah E

    2017-09-01

    Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. Case series and literature review. Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

  13. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  14. Spontaneous flocking in human groups.

    Science.gov (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete

    2013-01-01

    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek

    2014-04-01

    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  16. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C

    2006-10-01

    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  17. Nonrandom distribuion of chromosome breaks in cultured lymphocytes of normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Ayme, S.; Mattei, J.F.; Mattei, M.G.; Aurran, Y.; Giraud, F.

    1976-02-29

    Breakpoint distribution was studied from cultured lymphocytes on 7653 metaphases from 524 subjects whose karyotypes were normal. The mean break rate was 5% in both sexes. The frequency increased significantly after 40 years and varied during the year. The location of the breaks was very different from the expected random distribution. The break frequency for each chromosome was different according to the type of break (chromatid, simple chromosomal and chromosomal involving rearrangements). The location of the breaks was also studied according to the type of band and with respect to the centromere. A comparison between spontaneous breaks, x-ray induced breaks, breaks in Fanconi's anemia and in congenital rearrangements, show very significant differences.

  18. GIMAP5 Deficiency Is Associated with Increased AKT Activity in T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    Xi-Lin Chen

    Full Text Available Long-term survival of T lymphocytes in quiescent state is essential to maintain their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5 causes peripheral T lymphopenia due to spontaneous death of T cells. The underlying mechanism responsible for the disruption of quiescence in Gimap5 deficient T cells remains largely unknown. In this study, we show that loss of functional Gimap5 results in increased basal activation of mammalian target of rapamycin (mTOR, independent of protein phosphatase 2A (PP2A or AMP-activated protein kinase (AMPK. Our results suggest that the constitutive activation of the phosphoinositide 3-kinase (PI3K pathway may be one of the consequences of the absence of functional GIMAP5.

  19. Chromosome damage in G0 X-irradiated lymphocytes from patients with hereditary retinoblastoma

    International Nuclear Information System (INIS)

    Morten, J.E.; Harnden, D.G.; Taylor, A.M.

    1981-01-01

    The amount of chromosome damage in peripheral blood lymphocytes following 400 rads G0 X-irradiation in 10 of 11 hereditary retinoblastoma patients was shown to be intermediate between that in normals and damage in trisomy 21 patients. The difference between normals and hereditary retinoblastoma patients was small, it varied between hereditary retinoblastoma patients, and no difference was detected following 200 rads G0 X-irradiation. No difference was found in levels of spontaneous chromosome damage in hereditary retinoblastoma patients, trisomy 21 patients, and normals. These results suggest that, although sensitivity to ionizing radiation may be associated with hereditary retinoblastoma, the observed difference is so small that it is probably not the major effect of the gene predisposing to retinoblastoma

  20. The effect of ultraviolet radiation on early stages of activation of human lymphocytes: inhibition is independent of effects on DNA

    DEFF Research Database (Denmark)

    Castellanos, G; Owens, T; Rudd, C

    1982-01-01

    before mitogen was added to the cultures, but were unaffected if irradiation occurred after 16 h of culture in presence of Con A. Cells irradiated with 84 ergs/mm2 at the onset of culture with mitogen did not show the early increase of cation pump function which is a characteristic of stimulated......Low doses (30-84 ergs/mm2, 1 erg = 10(7) J) of ultraviolet radiation (UV) caused severe inhibition of the proliferation of human lymphocytes in vitro. Greatest inhibition was produced when resting cells were irradiated immediately prior to stimulation with concanavalin A (Con A); this was true...... lymphocytes, when this was measured by means of 86Rb uptake after 2-4 h culture. The mitogen-stimulated activation of cation pump function has previously been shown to be unaffected by concentrations of cycloheximide and actinomycin D which produce virtually complete inhibition of protein and RNA synthesis...

  1. In vitro effect of the antimalarial drug proguanil hydrochloride on viability and DNA damage in human peripheral blood lymphocytes.

    Science.gov (United States)

    Gajski, Goran; Dinter, Domagoj; Garaj-Vrhovac, Vera

    2010-11-01

    This study aimed to evaluate the effect of proguanil, a chemical substance used for treatment and prevention of malaria on viability and DNA integrity in human lymphocytes in vitro. Two different concentrations of proguanil obtained from the plasma concentrations were used: 130ng/ml used for prophylactic treatment and 520ng/ml used in treatment of malaria. Testing was done with and without metabolic activation. Viability of lymphocytes decreased in time and dose dependent manner. Comet assay parameters showed similar effects, indicating that some damage to DNA molecule can occur. Frequency of sister chromatid exchanges did not show significant deviation from the control samples. As for the proliferation kinetics no significant changes were noticed. Since majority of DNA damaging effect is induced after metabolic activation it is to be concluded that activity of proguanil is dependent upon the active metabolite cycloguanil and that monitoring should be conducted especially among frequent travellers. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. The effect of ultraviolet radiation on early stages of activation of human lymphocytes: inhibition is independent of effects on DNA

    DEFF Research Database (Denmark)

    Castellanos, G; Owens, T; Rudd, C

    1982-01-01

    Low doses (30-84 ergs/mm2, 1 erg = 10(7) J) of ultraviolet radiation (UV) caused severe inhibition of the proliferation of human lymphocytes in vitro. Greatest inhibition was produced when resting cells were irradiated immediately prior to stimulation with concanavalin A (Con A); this was true...... whether activation was measured by the incorporation of labelled leucine, uridine, or thymidine. If UV was applied at 44 h after culture in presence of Con A, the incorporation of [3H]thymidine measured 4 h later was seen to be inhibited but transcription and translation were scarcely affected. UV...... lymphocytes, when this was measured by means of 86Rb uptake after 2-4 h culture. The mitogen-stimulated activation of cation pump function has previously been shown to be unaffected by concentrations of cycloheximide and actinomycin D which produce virtually complete inhibition of protein and RNA synthesis...

  3. Signalling detection of DNA damage induced by low doses of ionizing radiation in human lymphocytes

    International Nuclear Information System (INIS)

    Valente, M.

    2011-01-01

    Individuals spontaneously present different sensitivities to ionizing radiation, measured by the severity of their post-radiotherapy side-effects. Cells from some patients with extreme clinical radiosensitivity have shown altered cellular radiosensitivity measured by different endpoints as apoptosis or DNA damage. Linking clinical and cellular sensitivity is of fundamental importance to establish a clinical test capable of predicting a person's radiosensitivity from a sample. Easily sampled, peripheral blood lymphocytes (PBL) are an appealing cellular model to study individual radiosensitivity as they have been shown to be the most radiosensitive hematopoietic cells. DNA damages and repair can be visualized by observing the kinetics of appearance and disappearance of gamma-H2AX foci on DNA double-strand breaks through immunofluorescence microscopy. The experimental strategy chosen here was to follow lymphocyte gamma-H2AX foci kinetics in response to different levels of irradiation as delayed gamma-H2AX foci disappearance has been observed in cells of individuals with high clinical radiosensitivity. For our initial study we irradiated in vitro samples of radiotherapy patients with different clinical radiosensitivities. The groups of distinct clinical sensitivities showed no corresponding differences in their cellular gamma-H2AX response. In addition, several samples were lost, mainly due to the long transportation period before being treated in our lab. To render this method usable for clinical applications, several changes were made: after improving sample viability, speed was increased by automation of image acquisition (Metasystem) and gamma-H2AX focus scoring (freeware CellProfiler). This technique was able to detect doses as low as 0.005 Gy and gave similar results to manual focus scoring. The possibility of discriminating different lymphocyte subsets (CD4, CD8 and CD19) during analysis was added to identify among the lymphocyte subsets the one producing more

  4. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

    Science.gov (United States)

    Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

    2017-08-01

    Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

  5. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  6. Proteome Dynamics in Biobanked Horse Peripheral Blood Derived Lymphocytes (PBL) with Induced Autoimmune Uveitis.

    Science.gov (United States)

    Hauck, Stefanie M; Lepper, Marlen F; Hertl, Michael; Sekundo, Walter; Deeg, Cornelia A

    2017-10-01

    Equine recurrent uveitis is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for 14 years since the initial experiment. Quantitative data could be acquired for 2632 proteins at all three time points. Profound changes (≥2-fold change) in PBL protein abundance were observed when comparing Day 0 with 15, representing acute inflammation (1070 regulated proteins) and Day 0 with 23 (cessation; 1571 regulated). Significant differences applied to proteins with functions in integrin signaling during active uveitis, involving "Erk and pi-3 kinase are necessary for collagen binding in corneal epithelia," "integrins in angiogenesis," and "integrin-linked kinase signaling" pathways. In contrast, at cessation of uveitic attack, significantly changed proteins belonged to pathways of "nongenotropic androgen signaling," "classical complement pathway," and "Amb2 integrin signaling." Several members of respective pathways were earlier shown to be changed in naturally occurring uveitis, underscoring the significance of these findings here and proofing the value of the induced model in mimicking spontaneous autoimmune uveitis. All MS data have been deposited to the ProteomeXchange consortium via the PRIDE partner repository (dataset identifier PXD005580). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Clock frequency estimation under spontaneous emission

    Science.gov (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong

    2018-02-01

    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  8. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta

    2013-11-01

    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  9. Spontaneous regression of an invasive thymoma.

    Science.gov (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko

    2009-05-01

    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  10. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.

    2001-01-01

    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  11. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    Science.gov (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  12. Pathological Investigation of Acquired Lymphangiectasia Accompanied by Lower Limb Lymphedema: Lymphocyte Infiltration in the Dermis and Epidermis.

    Science.gov (United States)

    Hara, Hisako; Mihara, Makoto; Anan, Takashi; Fukumoto, Takaya; Narushima, Mitsunaga; Iida, Takuya; Koshima, Isao

    2016-09-01

    Sometimes acquired lymphangiectasia (lymphangioma circumscriptum), the pathological mechanism of which is unknown, accompanies lymphedema. The purpose of this study was to better understand the pathological changes present in acquired lymphangiectasia. We examined the pathological characteristics of acquired lymphangiectasia with lymphedema among patients treated at the University of Tokyo Hospital from March 2008 to December 2015. In total, 16 biopsies from 10 patients were investigated. The average age of the patients was 57.2 years (range 43-69), and all were female with secondary lymphedema. Surgical specimens were fixed in formalin, and tissue sections were stained with hematoxylin-eosin. Additional immunostaining (podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE] -1, CD4, CD8, CD20, and CD31) was performed in cases 1-3 and 8-10. Dilation of lymphatic vessels in the papillary dermis was present in all 10 cases. Infiltration of inflammatory cells, most of which were lymphocytes, was also observed in the dermis and the epidermis in all cases, even though there were no clinical signs of inflammation. The infiltrating lymphocytes were mainly CD4+ T cells, and less commonly, CD8+ T cells and CD20+ B cells. The number of three types of lymphocytes was significantly larger in the superficial layer of the dermis than in the deep layer, which may indicate that they oozed out from the dilated lymphatic vessels located in the superficial dermis. CD8+ T cells infiltrated the epidermis in seven of eight specimens. In case 4, coagulated lymphatic fluid inside the lymphatic vessel was observed. Proliferation of collagenous fiber in the dermis and acanthosis were observed. Lymphatic dilation and proliferation of collagenous fiber in the dermis were seen in cases of acquired lymphangiectasia (lymphangioma circumscriptum). Constant infiltration of lymphocytes in the dermis and the epidermis may have a relation to frequent cellulitis, which is often seen in

  13. Cell kinetic and radiosensitivity of PHA stimulated goat lymphocytes

    International Nuclear Information System (INIS)

    Debuyst, B.; Rosenthal, M.; Leonard, A.

    1982-01-01

    The harlequin-staining method has been used to study the cell kinetic of goat peripheral blood lymphocytes stimulated by phytohemagglutinin and to assess their radiosensitivity. At 48 h, the standardized culture time employed for human lymphocytes, 71% of the goat lymphocytes are in first mitosis, 23% are in second mitosis and 5% in third. Irradiation with 200 rads X-rays induces an average of 24,5 dicentric chromosomes per hundred cells in first mitosis [fr

  14. Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection

    OpenAIRE

    Baliko, Z.; Szereday, L.; Szekeres-Bartho, J.

    1997-01-01

    BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. METHODS: Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes we...

  15. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator initiated phase 2 study

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Herman, Sarah E M; Maric, Irina

    2016-01-01

    PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress...... the chemoattraction of CLL cells. CONCLUSIONS: In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the anti-tumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL....

  16. [Immunological treatment of spontaneous repeated abortions. The value of transfusing the partner's leukocytes in the third week of gestation].

    Science.gov (United States)

    Sagot, P; Bignon, J D; Cesbron, A; Laurent, F X; Adjou, C; Muller, J Y

    1993-01-01

    Twenty-two nulli- all primipara who had had previous repeated spontaneous abortions and who did not have anti-HLA antibodies for the partner, received immunological treatment consisting of a single transfusion of the partner's lymphocytes in the third week of pregnancy, and giving natural progesterone supplements after the kinetic of Beta-HCG in the plasma had been assessed. The number of pregnancies which went to terme (94% success) was significantly better than those obtained in our first protocol which was to give one to three transfusions of the partner's lymphocytes before the pregnancy started (58% success rare after 24 treatments). Apart from obtaining much better results the second protocol made it possible to avoid giving a significant number of useless transfusions (22% of pre-conceptual transfusions were not followed by a pregnancy at all).

  17. Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

    Directory of Open Access Journals (Sweden)

    Tosti G

    2013-10-01

    Full Text Available Giulio Tosti, Emilia Cocorocchio, Elisabetta PennacchioliDivisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, ItalyAbstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4 antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under

  18. Non proliferation of nuclear weapons?

    International Nuclear Information System (INIS)

    Le Guelte, Georges

    2015-10-01

    After having evoked the behaviour of nuclear countries regarding the development of nuclear weapons and uranium procurement, or nuclear programmes after the Second World War until nowadays, the author presents the non proliferation Treaty (NPT) as a construction at the service of super-powers. He comments and discusses the role of the IAEA control system and its evolutions: a control limited to declared installations, an export control with the spectre of plutonium, a control system thwarted by some technological innovations, information systems coming in, and an additional protocol related to the application of guarantees. He comments the evolution of the context from a bipolar world to a world without pole which raises the issue of how to have commitments respected: description of the role and practice of non proliferation during the Cold War, after the Cold War, and in a world without governance

  19. Proliferation Vulnerability Red Team report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E. [and others

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  20. Soluble Factors Secreted by T Cells Promote β-Cell Proliferation

    Science.gov (United States)

    Dirice, Ercument; Kahraman, Sevim; Jiang, Wenyu; El Ouaamari, Abdelfattah; De Jesus, Dario F.; Teo, Adrian K.K.; Hu, Jiang; Kawamori, Dan; Gaglia, Jason L.; Mathis, Diane; Kulkarni, Rohit N.

    2014-01-01

    Type 1 diabetes is characterized by infiltration of pancreatic islets with immune cells, leading to insulin deficiency. Although infiltrating immune cells are traditionally considered to negatively impact β-cells by promoting their death, their contribution to proliferation is not fully understood. Here we report that islets exhibiting insulitis also manifested proliferation of β-cells that positively correlated with the extent of lymphocyte infiltration. Adoptive transfer of diabetogenic CD4+ and CD8+ T cells, but not B cells, selectively promoted β-cell proliferation in vivo independent from the effects of blood glucose or circulating insulin or by modulating apoptosis. Complementary to our in vivo approach, coculture of diabetogenic CD4+ and CD8+ T cells with NOD.RAG1−/− islets in an in vitro transwell system led to a dose-dependent secretion of candidate cytokines/chemokines (interleukin-2 [IL-2], IL-6, IL-10, MIP-1α, and RANTES) that together enhanced β-cell proliferation. These data suggest that soluble factors secreted from T cells are potential therapeutic candidates to enhance β-cell proliferation in efforts to prevent and/or delay the onset of type 1 diabetes. PMID:24089508