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Sample records for cell-extrinsic defective lymphocyte

  1. Cell-extrinsic defective lymphocyte development in Lmna(-/- mice.

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    J Scott Hale

    Full Text Available BACKGROUND: Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. PRINCIPAL FINDINGS: Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development. CONCLUSIONS: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

  2. Eosinophilic granuloma associated with a 16q22 chromosomal defect of cutaneous T lymphocytes.

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    Bisballe, S; Thestrup-Pedersen, K; Bjerring, P; Jensen, J J; Ottosen, P D; Kaltoft, K

    1984-01-01

    A 61-year-old woman presented with circumscribed eczematous eruptions with maceration, erosions and patchy infiltration in the perineum and inframammary regions. A diagnosis of eosinophilic granuloma (cutaneous histiocytosis X) was established. T lymphocytes from a skin biopsy were grown in vitro for three weeks after which chromosomal studies revealed a break or gap at chromosome 16q22 in 15% of the lymphocytes. The addition of alpha-interferon increased the percentage of affected cells to 28%. T lymphocytes from the patient's blood did not show the defect. The biological significance of the chromosomal defect is uncertain. It has been described before in healthy persons, malignant lymphoma, cold urticaria and IgA deficiency, and mental retardation. It has not been seen in patients with eosinophilic granuloma.

  3. The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles.

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    Christopher M Ziegler

    2016-03-01

    Full Text Available Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV matrix protein nor a functional endosomal sorting complex transport (ESCRT pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.

  4. Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion

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    de la Rosa, Jorge; Freije, José M. P.; Cabanillas, Rubén; Osorio, Fernando G.; Fraga, Mario F.; Fernández-García, M. Soledad; Rad, Roland; Fanjul, Víctor; Ugalde, Alejandro P.; Liang, Qi; Prosser, Haydn M.; Bradley, Allan; Cadiñanos, Juan; López-Otín, Carlos

    2013-01-01

    Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A accumulating) and Zmpste24-proficient (mature lamin A containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target. PMID:23917225

  5. Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion.

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    de la Rosa, Jorge; Freije, José M P; Cabanillas, Rubén; Osorio, Fernando G; Fraga, Mario F; Fernández-García, M Soledad; Rad, Roland; Fanjul, Víctor; Ugalde, Alejandro P; Liang, Qi; Prosser, Haydn M; Bradley, Allan; Cadiñanos, Juan; López-Otín, Carlos

    2013-01-01

    Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A-accumulating) and Zmpste24-proficient (mature lamin A-containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target.

  6. ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells.

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    Kwok, Marwan; Davies, Nicholas; Agathanggelou, Angelo; Smith, Edward; Oldreive, Ceri; Petermann, Eva; Stewart, Grant; Brown, Jeff; Lau, Alan; Pratt, Guy; Parry, Helen; Taylor, Malcolm; Moss, Paul; Hillmen, Peter; Stankovic, Tatjana

    2016-02-04

    TP53 and ataxia telangiectasia mutated (ATM) defects are associated with genomic instability, clonal evolution, and chemoresistance in chronic lymphocytic leukemia (CLL). Currently, therapies capable of providing durable remissions in relapsed/refractory TP53- or ATM-defective CLL are lacking. Ataxia telangiectasia and Rad3-related (ATR) mediates response to replication stress, the absence of which leads to collapse of stalled replication forks into chromatid fragments that require resolution through the ATM/p53 pathway. Here, using AZD6738, a novel ATR kinase inhibitor, we investigated ATR inhibition as a synthetically lethal strategy to target CLL cells with TP53 or ATM defects. Irrespective of TP53 or ATM status, induction of CLL cell proliferation upregulated ATR protein, which then became activated in response to replication stress. In TP53- or ATM-defective CLL cells, inhibition of ATR signaling by AZD6738 led to an accumulation of unrepaired DNA damage, which was carried through into mitosis because of defective cell cycle checkpoints, resulting in cell death by mitotic catastrophe. Consequently, AZD6738 was selectively cytotoxic to both TP53- and ATM-defective CLL cell lines and primary cells. This was confirmed in vivo using primary xenograft models of TP53- or ATM-defective CLL, where treatment with AZD6738 resulted in decreased tumor load and reduction in the proportion of CLL cells with such defects. Moreover, AZD6738 sensitized TP53- or ATM-defective primary CLL cells to chemotherapy and ibrutinib. Our findings suggest that ATR is a promising therapeutic target for TP53- or ATM-defective CLL that warrants clinical investigation.

  7. Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.

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    Luisa Lorenzi

    Full Text Available Hermansky Pudlak type 2 syndrome (HPS2 is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene. The defect results in the impairment of the adaptor protein 3 (AP-3 complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(brightCD16(- Natural Killer (NK cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

  8. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

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    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  9. Smooth muscle cell-extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy.

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    Wheeler, Matthew T; Allikian, Michael J; Heydemann, Ahlke; Hadhazy, Michele; Zarnegar, Sara; McNally, Elizabeth M

    2004-03-01

    Vascular spasm is a poorly understood but critical biomedical process because it can acutely reduce blood supply and tissue oxygenation. Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage. In the heart, sarcoglycan gene mutations produce regional defects in membrane permeability and focal degeneration, and it was hypothesized that vascular spasm was responsible for this focal necrosis. Supporting this notion, vascular spasm was noted in coronary arteries, and disruption of the sarcoglycan complex was observed in vascular smooth muscle providing a molecular mechanism for spasm. Using a transgene rescue strategy in the background of sarcoglycan-null mice, we replaced cardiomyocyte sarcoglycan expression. Cardiomyocyte-specific sarcoglycan expression was sufficient to correct cardiac focal degeneration. Intriguingly, successful restoration of the cardiomyocyte sarcoglycan complex also eliminated coronary artery vascular spasm, while restoration of smooth muscle sarcoglycan in the background of sarcoglycan-null alleles did not. This mechanism, whereby tissue damage leads to vascular spasm, can be partially corrected by NO synthase inhibitors. Therefore, we propose that cytokine release from damaged cardiomyocytes can feed back to produce vascular spasm. Moreover, vascular spasm feeds forward to produce additional cardiac damage.

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

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    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.

  11. Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8⁺ T cell priming.

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    Mahadevan, Navin R; Anufreichik, Veronika; Rodvold, Jeffrey J; Chiu, Kevin T; Sepulveda, Homero; Zanetti, Maurizio

    2012-01-01

    Tumor-infiltrating myeloid cells, such as dendritic cells (BMDC), are key regulators of tumor growth. However, the tumor-derived signals polarizing BMDC to a phenotype that subverts cell-mediated anti-tumor immunity have yet to be fully elucidated. Addressing this unresolved problem we show that the tumor unfolded protein response (UPR) can function in a cell-extrinsic manner via the transmission of ER stress (TERS) to BMDC. TERS-imprinted BMDC upregulate the production of pro-inflammatory, tumorigenic cytokines but also the immunosuppressive enzyme arginase. Importantly, they downregulate cross-presentation of high-affinity antigen and fail to effectively cross-prime CD8(+) T cells, causing T cell activation without proliferation and similarly dominantly suppress cross-priming by bystander BMDC. Lastly, TERS-imprinted BMDC facilitate tumor growth in vivo with fewer tumor-infiltrating CD8(+) T cells. In sum, we demonstrate that tumor-borne ER stress imprints ab initio BMDC to a phenotype that recapitulates several of the inflammatory/suppressive characteristics ascribed to tumor-infiltrating myeloid cells, highlighting the tumor UPR as a critical controller of anti-tumor immunity and a new target for immune modulation in cancer.

  12. Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8⁺ T cell priming.

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    Navin R Mahadevan

    Full Text Available Tumor-infiltrating myeloid cells, such as dendritic cells (BMDC, are key regulators of tumor growth. However, the tumor-derived signals polarizing BMDC to a phenotype that subverts cell-mediated anti-tumor immunity have yet to be fully elucidated. Addressing this unresolved problem we show that the tumor unfolded protein response (UPR can function in a cell-extrinsic manner via the transmission of ER stress (TERS to BMDC. TERS-imprinted BMDC upregulate the production of pro-inflammatory, tumorigenic cytokines but also the immunosuppressive enzyme arginase. Importantly, they downregulate cross-presentation of high-affinity antigen and fail to effectively cross-prime CD8(+ T cells, causing T cell activation without proliferation and similarly dominantly suppress cross-priming by bystander BMDC. Lastly, TERS-imprinted BMDC facilitate tumor growth in vivo with fewer tumor-infiltrating CD8(+ T cells. In sum, we demonstrate that tumor-borne ER stress imprints ab initio BMDC to a phenotype that recapitulates several of the inflammatory/suppressive characteristics ascribed to tumor-infiltrating myeloid cells, highlighting the tumor UPR as a critical controller of anti-tumor immunity and a new target for immune modulation in cancer.

  13. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

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    M Lia Palomba

    Full Text Available PURPOSE: Chronic Lymphocytic Leukemia (CLL is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR. Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK and distal (pPLCγ2, pBLNK, ppERK phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

  14. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

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    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.

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

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    2013-08-20

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

  16. What Is Chronic Lymphocytic Leukemia?

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

  17. Evaluation of lymphocyte subgroups in children with subacute sclerosing panencephalitis.

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    Yilmaz, C; Yuca, S A; Yilmaz, N; Oner, A F; Caksen, H

    2009-01-01

    The aetiology of subacute sclerosing panencephalitis (SSPE) remains to be fully elucidated, although it follows infection with a hypermutant defective M-protein measles virus. This study analysed peripheral blood lymphocyte subgroups to determine their role in the pathophysiology of SSPE. It included 22 children with SSPE aged 2 - 15 years (patient group) and 22 age- and gender-matched healthy children (control group). In children or= 6 years old, there were no significant differences in the lymphocyte subgroups. In conclusion, these findings suggest that a low CD4(+) lymphocyte count might be responsible for SSPE in younger children.

  18. Acute Lymphocytic Leukemia

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

  19. Chemokines, lymphocytes, and HIV

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    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

  20. LYMPHOCYTE APOPTOSIS IN PSORIASIS

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    О. M. Kapuler

    2006-01-01

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

  1. Paravaginal defect

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    Arenholt, Louise T S; Pedersen, Bodil Ginnerup; Glavind, Karin;

    2016-01-01

    , arcus tendineus fascia pelvis (ATFP), pubocervical fascia, and uterosacral/cardinal ligaments. Studies conclude that physical examination is inconsistent in detecting paravaginal defects. Ultrasound (US) and magnetic resonance imaging (MRI) have been used to describe patterns in the appearance...

  2. T-lymphocyte subset dynamics in well-treated HIV-infected men during a bout of exhausting exercise

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    Dirksen, Carsten; Hansen, Birgitte R; Kolte, Lilian

    2015-01-01

    In healthy individuals the substantial lymphocytosis during a bout of exhausting exercise constitutes primarily mature T cells from the peripheral lymphoid organs but naïve T cells are also recruited. This study investigated whether the defective CD4 + T-lymphocyte count in peripheral blood during......-infected patients are also reflected in defective acutely mobilized active immune cells following exhausting exercise. The CD4 + T-lymphocyte count is highly sensitive to physical activity....

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

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

    2008-01-21

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

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

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    2016-10-04

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

  5. Facts about Birth Defects

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    ... Heart Defects Atrial Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great ... Defects Fetal Alcohol Syndrome Disorders Gastroschisis Heart Defects Coarctation of the Aorta Hypoplastic left heart syndrome Tetralogy ...

  6. Lymphocyte Trafficking to Mucosal Tissues

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

    2015-01-01

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

  7. Lymphocyte 'homing' and chronic inflammation.

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    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

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

  8. Lymphocytic Interstitial Pneumonia.

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

    2016-09-01

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

  9. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

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

    2015-01-01

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

  10. Chronic lymphocytic leukaemia

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

    2017-01-01

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

  11. Local administration of autologous platelet-rich plasma in a female patient with skin ulcer defect

    Directory of Open Access Journals (Sweden)

    S M Noskov

    2011-01-01

    Full Text Available The paper describes a clinical observation of the efficiency of local therapy with autologous platelet-rich plasma for .skin ulcer defect in a female with chronic lymphocytic leukemia

  12. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

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

  13. 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 tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full re...... 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....

  14. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2007-10-01

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

  15. T-lymphocyte subset dynamics in well-treated HIV-infected men during a bout of exhausting exercise.

    Science.gov (United States)

    Dirksen, Carsten; Hansen, Birgitte R; Kolte, Lilian; Haugaard, Steen B; Andersen, Ove

    2015-01-01

    In healthy individuals the substantial lymphocytosis during a bout of exhausting exercise constitutes primarily mature T cells from the peripheral lymphoid organs but naïve T cells are also recruited. This study investigated whether the defective CD4 + T-lymphocyte count in peripheral blood during rest in human immunodeficiency virus (HIV)-infected patients would also be observed following a maximal output ergometer bicycle test. At rest, in 45 well-treated HIV-infected patients, mature and naïve CD4 + T-lymphocyte counts were decreased whereas the less immune active CD8 + T lymphocytes were increased compared with 10 healthy control subjects. In response to exercise mature and naïve CD4 + T lymphocytes increased less and mature and naïve CD8 + T lymphocytes increased most in HIV-infected patients. In conclusion, defective resting mature and naïve CD4 + T lymphocytes in well-treated HIV-infected patients are also reflected in defective acutely mobilized active immune cells following exhausting exercise. The CD4 + T-lymphocyte count is highly sensitive to physical activity.

  16. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    Energy Technology Data Exchange (ETDEWEB)

    Harris, G. (Kennedy Inst. of Rheumatology, London (UK). Div. of Experimental Pathology); Cramp, W.A.; Edwards, J.C.; George, A.M.; Sabovljev, S.A.; Hart, L.; Hughes, G.R.V. (Hammersmith Hospital, London (UK)); Denman, A.M. (Northwich Park Hospital, Harrow (UK)); Yatvin, M.B. (Wisconsin Clinical Cancer Center, Madison (USA))

    1985-06-01

    The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  18. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  19. Ventricular septal defect (image)

    Science.gov (United States)

    Ventricular septal defect is a congenital defect of the heart, that occurs as an abnormal opening in ... wall that separates the right and left ventricles. Ventricular septal defect may also be associated with other ...

  20. Studies on rabbit lymphocytes in vitro

    Science.gov (United States)

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

    1969-01-01

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

  1. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  2. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    Science.gov (United States)

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

    2017-01-01

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

  3. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  4. 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.

  5. 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

  6. Glucose-dependent de Novo Lipogenesis in B Lymphocytes

    Science.gov (United States)

    Dufort, Fay J.; Gumina, Maria R.; Ta, Nathan L.; Tao, Yongzhen; Heyse, Shannon A.; Scott, David A.; Richardson, Adam D.; Seyfried, Thomas N.; Chiles, Thomas C.

    2014-01-01

    Bacterially derived lipopolysaccharide (LPS) stimulates naive B lymphocytes to differentiate into immunoglobulin (Ig)-secreting plasma cells. Differentiation of B lymphocytes is characterized by a proliferative phase followed by expansion of the intracellular membrane secretory network to support Ig production. A key question in lymphocyte biology is how naive B cells reprogram metabolism to support de novo lipogenesis necessary for proliferation and expansion of the endomembrane network in response to LPS. We report that extracellularly acquired glucose is metabolized, in part, to support de novo lipogenesis in response to LPS stimulation of splenic B lymphocytes. LPS stimulation leads to increased levels of endogenous ATP-citrate lyase (ACLY), and this is accompanied by increased ACLY enzymatic activity. ACLY produces cytosolic acetyl-CoA from mitochondrially derived citrate. Inhibition of ACLY activity in LPS-stimulated B cells with the selective inhibitor 2-hydroxy-N-arylbenzenesulfonamide (compound-9; C-9) blocks glucose incorporation into de novo lipid biosynthesis, including cholesterol, free fatty acids, and neutral and acidic phospholipids. Moreover, inhibition of ACLY activity in splenic B cells results in inhibition of proliferation and defective endomembrane expansion and reduced expression of CD138 and Blimp-1, markers for plasma-like B cell differentiation. ACLY activity is also required for LPS-induced IgM production in CH12 B lymphoma cells. These data demonstrate that ACLY mediates glucose-dependent de novo lipogenesis in response to LPS signaling and identify a role for ACLY in several phenotypic changes that define plasma cell differentiation. PMID:24469453

  7. Congenital platelet function defects

    Science.gov (United States)

    ... storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... Congenital platelet function defects are bleeding disorders that ... function, even though there are normal platelet numbers. Most ...

  8. Defect production in ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States); Kinoshita, C. [Kyushu Univ. (Japan)

    1997-08-01

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si{sub 3}N{sub 4}), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed.

  9. Lymphocyte subpopulations in Sheehan's syndrome.

    Science.gov (United States)

    Atmaca, Hulusi; Araslı, Mehmet; Yazıcı, Zihni Acar; Armutçu, Ferah; Tekin, Ishak Özel

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

  10. 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.

  11. 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.

  12. Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

    NARCIS (Netherlands)

    Ormai, S.; Hagenbeek, A.; Palkovits, M.; Bekkum, D.W. van

    1973-01-01

    The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administra

  13. Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.

    Directory of Open Access Journals (Sweden)

    Chi Wang Ip

    Full Text Available Mice overexpressing proteolipid protein (PLP develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.

  14. Imaging defects and dopants

    Directory of Open Access Journals (Sweden)

    H.Philipp Ebert

    2003-06-01

    With the invention of the transistor, a revolution in the development of semiconductor-based electronic devices began. However, even in the very early stages, the importance of defects and dopant atoms became obvious. In fact, if one incorporates the right defects and dopant atoms into semiconductor materials, one can tune their electrical properties such that optimal device characteristics are achieved. Unfortunately, counteractive defects are often also formed unintentionally during semiconductor processing, leading to unfavorable electronic properties. Considerable research efforts have, therefore, focused on understanding the nanoscale physics that governs the formation of point defects, the incorporation behavior of impurities, and their respective electronic properties.

  15. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  16. 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.

  17. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  18. Birth Defects (For Parents)

    Science.gov (United States)

    ... this virus during pregnancy, her child may have low birth weight, intellectual disability (mental retardation) or learning disabilities, ... and central nervous system problems. A child with late congenital syphilis may have abnormalities of the ... Diagnosing Birth Defects Many birth defects are diagnosed even before ...

  19. [Evolution and phylogeny of B lymphocytes].

    Science.gov (United States)

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

    B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  20. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  1. Cosmic defects and cosmology

    CERN Document Server

    Magueijo, J; Magueijo, Joao; Brandenberger, Robert

    2000-01-01

    We provide a pedagogical overview of defect models of structure formation. We first introduce the concept of topological defect, and describe how to classify them. We then show how defects might be produced in phase transitions in the Early Universe and approach non-pathological scaling solutions. A very heuristic account of structure formation with defects is then provided, following which we introduce the tool box required for high precision calculations of CMB and LSS power spectra in these theories. The decomposition into scalar vector and tensor modes is reviewed, and then we introduce the concept of unequal-time correlator. We use isotropy and causality to constrain the form of these correlators. We finally show how these correlators may be decomposed into eigenmodes, thereby reducing a defect problem to a series of ``inflation'' problems. We conclude with a short description of results in these theories and how they fare against observations. We finally describe yet another application of topological d...

  2. Impaired humoral immunity in X-linked lymphoproliferative disease is associated with defective IL-10 production by CD4+ T cells

    Science.gov (United States)

    Ma, Cindy S.; Hare, Nathan J.; Nichols, Kim E.; Dupré, Loic; Andolfi, Grazia; Roncarolo, Maria-Grazia; Adelstein, Stephen; Hodgkin, Philip D.; Tangye, Stuart G.

    2005-01-01

    X-linked lymphoproliferative disease (XLP) is an often-fatal immunodeficiency characterized by hypogammaglobulinemia, fulminant infectious mononucleosis, and/or lymphoma. The genetic lesion in XLP, SH2D1A, encodes the adaptor protein SAP (signaling lymphocytic activation molecule–associated [SLAM-associated] protein); however, the mechanism(s) by which mutations in SH2D1A causes hypogammaglobulinemia is unknown. Our analysis of 14 XLP patients revealed normal B cell development but a marked reduction in the number of memory B cells. The few memory cells detected were IgM+, revealing deficient isotype switching in vivo. However, XLP B cells underwent proliferation and differentiation in vitro as efficiently as control B cells, which indicates that the block in differentiation in vivo is B cell extrinsic. This possibility is supported by the finding that XLP CD4+ T cells did not efficiently differentiate into IL-10+ effector cells or provide optimal B cell help in vitro. Importantly, the B cell help provided by SAP-deficient CD4+ T cells was improved by provision of exogenous IL-10 or ectopic expression of SAP, which resulted in increased IL-10 production by T cells. XLP CD4+ T cells also failed to efficiently upregulate expression of inducible costimulator (ICOS), a potent inducer of IL-10 production by CD4+ T cells. Thus, insufficient IL-10 production may contribute to hypogammaglobulinemia in XLP. This finding suggests new strategies for treating this immunodeficiency. PMID:15761493

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

    Science.gov (United States)

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

    2002-01-01

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

  4. GTPase of the Immune-Associated Nucleotide Protein 5 Regulates the Lysosomal Calcium Compartment in T Lymphocytes

    Science.gov (United States)

    Serrano, Daniel; Ghobadi, Farnaz; Boulay, Guylain; Ilangumaran, Subburaj; Lavoie, Christine; Ramanathan, Sheela

    2017-01-01

    T lymphocytes from Gimap5lyp/lyp rats carrying a recessive mutation in the GTPase of immune-associated protein 5 (Gimap5) gene undergo spontaneous apoptosis. Molecular mechanisms underlying this survival defect are not yet clear. We have shown that Gimap5lyp/lyp T lymphocytes display reduced calcium influx following T cell antigen receptor (TCR) stimulation that was associated with impaired buffering of calcium by mitochondria. Here, we investigated the subcellular localization of GIMAP5 and its influence on Ca2+ response in HEK293T cells and T lymphocytes. The more abundantly expressed GIMAP5v2 localizes to the lysosome and certain endosomal vesicles. Gimap5lyp/lyp T lymphocytes showed increased accumulation of calcium in the lysosomes as evidenced by Gly-Phe β-naphthylamide (GPN) triggered Ca2+ release. As a corollary, GPN-induced Ca2+ flux was decreased in HEK293T cells expressing GIMAP5v2. Strikingly, TCR stimulation of rat, mouse, and human T lymphocytes increased lysosomal calcium content. Overall, our findings show that lysosomes modulate cellular Ca2+ response during T cell activation and that GIMAP5 regulates the lysosomal Ca2+ compartment in T lymphocytes. PMID:28223986

  5. 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.

  6. Diabetes mellitus and birth defects

    Science.gov (United States)

    Correa, Adolfo; Gilboa, Suzanne M.; Besser, Lilah M.; Botto, Lorenzo D.; Moore, Cynthia A.; Hobbs, Charlotte A.; Cleves, Mario A.; Riehle-Colarusso, Tiffany J.; Waller, D. Kim; Reece, E. Albert

    2016-01-01

    OBJECTIVE The purpose of this study was to examine associations between diabetes mellitus and 39 birth defects. STUDY DESIGN This was a multicenter case-control study of mothers of infants who were born with (n = 13,030) and without (n = 4895) birth defects in the National Birth Defects Prevention Study (1997–2003). RESULTS Pregestational diabetes mellitus (PGDM) was associated significantly with noncardiac defects (isolated, 7/23 defects; multiples, 13/23 defects) and cardiac defects (isolated, 11/16 defects; multiples, 8/16 defects). Adjusted odds ratios for PGDM and all isolated and multiple defects were 3.17 (95% CI, 2.20–4.99) and 8.62 (95% CI, 5.27–14.10), respectively. Gestational diabetes mellitus (GDM) was associated with fewer noncardiac defects (isolated, 3/23 defects; multiples, 3/23 defects) and cardiac defects (isolated, 3/16 defects; multiples, 2/16 defects). Odds ratios between GDM and all isolated and multiple defects were 1.42 (95% CI, 1.17–1.73) and 1.50 (95% CI, 1.13–2.00), respectively. These associations were limited generally to offspring of women with prepregnancy body mass index ≥25 kg/m2. CONCLUSION PGDM was associated with a wide range of birth defects; GDM was associated with a limited group of birth defects. PMID:18674752

  7. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  8. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. Obinutuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

    Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents.

  10. 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.

  11. Chronic lymphocytic leukemia: present status.

    Science.gov (United States)

    Montserrat, E; Rozman, C

    1995-03-01

    Chronic lymphocytic leukemia (CLL) is the form of leukemia which occurs most frequently in Western countries. Its etiology is unknown, and no relationship with viruses or genes has been demonstrated. Epidemiological data suggest that genetic and ambiental factors might be of some significance. Clinical features of CLL are due to the accumulation of leukemic cells in bone marrow and lymphoid organs as well as the immune disturbances that accompany the disease. The prognosis of patients with CLL varies. Treatment is usually indicated by the risk of the individual patient, which is clearly reflected by the stage of the disease. In the early stage (Binet A, Rai O) it is reasonable to defer therapy until disease progression is observed. By contrast, because their median survival is less than five years, patients with more advanced stages require therapy. For almost 50 years, no major advances in the management of CLL, which has revolved around the use of alkylating agents, have been made. In recent years, the therapeutic approach in patients with CLL has changed as a result of the introduction of combination chemotherapy regimens and, in particular, purine analogues. The latter are already the treatment of choice for patients not responding to standard therapies, and their role as front-line therapy is being investigated. Bone marrow transplants are also being increasingly used. It is to be hoped that in years to come the outcome of patients with CLL will be improved by these advances.

  12. Adults with Congenital Heart Defects

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Web Booklet: Adults With Congenital Heart Defects Updated:Apr 24,2014 From the Committee on ... below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: Adults with Congenital Heart Defects Introduction: ...

  13. What Are Congenital Heart Defects?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Congenital Heart Defects? Congenital (kon-JEN-ih-tal) heart defects are problems ... carry blood to the heart or the body Congenital heart defects change the normal flow of blood through the ...

  14. What Are Neural Tube Defects?

    Science.gov (United States)

    ... NICHD Research Information Clinical Trials Resources and Publications Neural Tube Defects (NTDs): Condition Information Skip sharing on social media links Share this: Page Content What are neural tube defects? Neural (pronounced NOOR-uhl ) tube defects are ...

  15. Expression of tenascin in lymphocytic autoimmune thyroiditis.

    OpenAIRE

    Back, W; Heubner, C; Winter, J.; Bleyl, U

    1997-01-01

    AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all act...

  16. Prenatal ontogeny of lymphocyte subpopulations in pigs.

    Science.gov (United States)

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

    1998-12-01

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

  17. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-24

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  18. Defect Prevention Based on 5 Dimensions of Defect Origin

    Directory of Open Access Journals (Sweden)

    Sakthi Kumaresh

    2012-08-01

    Full Text Available “Discovering the unexpected is more important than confirming the known [7]. In software development,the “unexpected” one relates to defects. These defects when unattended would cause failure to the productand risk to the users. The increasing dependency of society on software and the crucial consequences that afailure can cause requires the need to find out the defects at the origin itself. Based on the lessons learntfrom the earlier set of projects, a defect framework highlighting the 5 Dimensions (Ds of defect origin isproposed in this work. The defect framework is based on analyzing the defects that had emerged fromvarious stages of software development like Requirements, Design, Coding, Testing and Timeline (defectsdue to lack of time during development. This study is not limited to just identifying the origin of defects atvarious phases of software development but also finds out the reasons for such defects, and defectpreventive (DP measures are proposed for each type of defect. This work can help practitioners chooseeffective defect avoidance measures.In addition to arriving at defect framework, this work also proposes a defect injection metric based onseverity of the defect rather than just defect count, which gives the number of adjusted defects produced bya project at various phases. The defect injection metric value, once calculated, serves as a yardstick tomake a comparison in the improvements made in the software process development between similar set ofprojects

  19. Single Ventricle Defects

    Science.gov (United States)

    ... artery and blood reaches the aorta through a patent ductus arteriosus (see diagram). How does the defect affect my ... only source of lung blood flow is the patent ductus arteriosus (PDA), an open passageway between the pulmonary artery ...

  20. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  1. Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE

    Science.gov (United States)

    Ferrando, Tiziana; Poggi, Alessandro; Garuti, Anna; D'Urso, Agustina; Selmo, Martina; Benvenuto, Federica; Cea, Michele; Zoppoli, Gabriele; Moran, Eva; Soncini, Debora; Ballestrero, Alberto; Sordat, Bernard; Patrone, Franco; Mostoslavsky, Raul; Uccelli, Antonio; Nencioni, Alessio

    2009-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-γ and TNF-α production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD+-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD+ depletion. In addition, we relate defective IFN-γ and TNF-α production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders. PMID:19936064

  2. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE.

    Directory of Open Access Journals (Sweden)

    Santina Bruzzone

    Full Text Available Nicotinamide phosphoribosyltransferase (Nampt inhibitors such as FK866 are potent inhibitors of NAD(+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD(+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-gamma and TNF-alpha production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD(+-degrading enzyme poly-(ADP-ribose-polymerase (PARP by activated T cells enhances their susceptibility to NAD(+ depletion. In addition, we relate defective IFN-gamma and TNF-alpha production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders.

  3. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE.

    Science.gov (United States)

    Bruzzone, Santina; Fruscione, Floriana; Morando, Sara; Ferrando, Tiziana; Poggi, Alessandro; Garuti, Anna; D'Urso, Agustina; Selmo, Martina; Benvenuto, Federica; Cea, Michele; Zoppoli, Gabriele; Moran, Eva; Soncini, Debora; Ballestrero, Alberto; Sordat, Bernard; Patrone, Franco; Mostoslavsky, Raul; Uccelli, Antonio; Nencioni, Alessio

    2009-11-19

    Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD(+) synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD(+) depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-gamma and TNF-alpha production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD(+)-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD(+) depletion. In addition, we relate defective IFN-gamma and TNF-alpha production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders.

  4. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...

  5. Rag defects and thymic stroma: lessons from animal models

    Directory of Open Access Journals (Sweden)

    Veronica eMarrella

    2014-06-01

    Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

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

    Science.gov (United States)

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

    2013-06-01

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

  7. CD229 (Ly9) lymphocyte cell surface receptor interacts homophilically through its N-terminal domain and relocalizes to the immunological synapse

    NARCIS (Netherlands)

    Romero, [No Value; Zapater, N; Calvo, M; Kalko, SG; de la Fuente, MA; Tovar, [No Value; Ockeloen, C; Pizcueta, P; Engel, P

    2005-01-01

    CD229 is a member of the CD150 family of the Ig superfamily expressed on T and B cells. Receptors of this family regulate cytokine production and cytotoxicity of lymphocytes and NK cells. The cytoplasmic tail of CD229 binds to SAP, a protein that is defective in X-linked lymphoproliferative syndrome

  8. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  9. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

    Full Text Available Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

  10. 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.

  11. Norwegian Pitched Roof Defects

    Directory of Open Access Journals (Sweden)

    Lars Gullbrekken

    2016-06-01

    Full Text Available The building constructions investigated in this work are pitched wooden roofs with exterior vertical drainpipes and wooden load-bearing system. The aim of this research is to further investigate the building defects of pitched wooden roofs and obtain an overview of typical roof defects. The work involves an analysis of the building defect archive from the research institute SINTEF Building and Infrastructure. The findings from the SINTEF archive show that moisture is a dominant exposure factor, especially in roof constructions. In pitched wooden roofs, more than half of the defects are caused by deficiencies in design, materials, or workmanship, where these deficiencies allow moisture from precipitation or indoor moisture into the structure. Hence, it is important to increase the focus on robust and durable solutions to avoid defects both from exterior and interior moisture sources in pitched wooden roofs. Proper design of interior ventilation and vapour retarders seem to be the main ways to control entry from interior moisture sources into attic and roof spaces.

  12. Discrete torsion defects

    CERN Document Server

    Brunner, Ilka; Plencner, Daniel

    2014-01-01

    Orbifolding two-dimensional quantum field theories by a symmetry group can involve a choice of discrete torsion. We apply the general formalism of `orbifolding defects' to study and elucidate discrete torsion for topological field theories. In the case of Landau-Ginzburg models only the bulk sector had been studied previously, and we re-derive all known results. We also introduce the notion of `projective matrix factorisations', show how they naturally describe boundary and defect sectors, and we further illustrate the efficiency of the defect-based approach by explicitly computing RR charges. Roughly half of our results are not restricted to Landau-Ginzburg models but hold more generally, for any topological field theory. In particular we prove that for a pivotal bicategory, any two objects of its orbifold completion that have the same base are orbifold equivalent. Equivalently, from any orbifold theory (including those based on nonabelian groups) the original unorbifolded theory can be be obtained by orbifo...

  13. Mask Blank Defect Detection

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, M A; Sommargren, G E

    2000-02-04

    Mask blanks are the substrates that hold the master patterns for integrated circuits. Integrated circuits are semiconductor devices, such as microprocessors (mPs), dynamic random access memory (DRAMs), and application specific integrated circuits (ASICs) that are central to the computer, communication, and electronics industries. These devices are fabricated using a set of master patterns that are sequentially imaged onto light-sensitive coated silicon wafers and processed to form thin layers of insulating and conductive materials on top of the wafer. These materials form electrical paths and transistors that control the flow of electricity through the device. For the past forty years the semiconductor industry has made phenomenal improvements in device functionality, compactness, speed, power, and cost. This progress is principally due to the exponential decrease in the minimum feature size of integrated circuits, which has been reduced by a factor of {radical}2 every three years. Since 1992 the Semiconductor Industry Association (SIA) has coordinated the efforts of producing a technology roadmap for semiconductors. In the latest document, ''The International Technology Roadmap for Semiconductors: 1999'', future technology nodes (minimum feature sizes) and targeted dates were specified and are summarized in Table 1. Lithography is the imaging technology for producing a de-magnified image of the mask on the wafer. A typical de-magnification factor is 4. Mask blank defects as small as one-eighth the equivalent minimum feature size are printable and may cause device failure. Defects might be the result of the surface preparation, such as polishing, or contamination due to handling or the environment. Table 2 shows the maximum tolerable defect sizes on the mask blank for each technology node. This downward trend puts a tremendous burden on mask fabrication, particularly in the area of defect detection and reduction. A new infrastructure for mask

  14. Nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.

  15. Supersymmetric k-defects

    CERN Document Server

    Koehn, Michael

    2015-01-01

    In supersymmetric theories, topological defects can have nontrivial behaviors determined purely by whether or not supersymmetry is restored in the defect core. A well-known example of this is that some supersymmetric cosmic strings are automatically superconducting, leading to important cosmological effects and constraints. We investigate the impact of nontrivial kinetic interactions, present in a number of particle physics models of interest in cosmology, on the relationship between supersymmetry and supercurrents on strings. We find that in some cases it is possible for superconductivity to be disrupted by the extra interactions.

  16. Congenital Abdominal Wall Defects

    DEFF Research Database (Denmark)

    Risby, Kirsten; Jakobsen, Marianne Skytte; Qvist, Niels

    2016-01-01

    complications were seen in five (15%) children: four had detachment of the mesh and one patient developed abdominal compartment syndrome. Mesh related clinical infection was observed in five children. In hospital mortality occurred in four cases (2 gastroschisis and 2 omphalocele) and was not procedure......OBJECTIVE: To evaluate the clinical utility of GORE® DUALMESH (GDM) in the staged closure of large congenital abdominal wall defects. MATERIALS AND METHODS: Data of patients with congenital abdominal wall defects managed with GDM was analyzed for outcome regarding complete fascial closure; mesh...

  17. Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Sarah J McCaskey; Elizabeth A Rondini; Jonathan F Clinthorne; Ingeborg M Langohr; Elizabeth M Gardner; Jenifer I Fenton

    2012-01-01

    AIM:To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with HeliCobacter hepaticus (H.hepaticus).METHODS:SMAD3-/-(n =19) and colitis-resistant SMAD3+/-(n =24) mice (8-10 wk of age) were infected with H.hepaticus and changes in immune cell populations [T lymphocytes,natural killer (NK) cells,T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d,3 d,7 d and 28 d post-infection using flow cytometry.Genotypedependent changes in T lymphocytes and granzyme B+ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.RESULTS:As previously observed,SMAD3-/-,but not SMAD3+/-mice,developed colitis,peaking at 4 wk post-infection.No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point.However,CD4+ and CD8+/CD62L10 cells,an effector T lymphocyte population,as well as NK cells (NKp46/DX5+) were significantly higher in the MsLNs of SMAD3-/-mice at 7 d and 28 d post-infection.In the colon,a higher number of CD3+ cells were present in SMAD3-/-compared to SMAD3+/-mice at baseline,which did not significantly change during infection.However,the number of granzyme B+ cells,a marker of cytolytic lymphocytes,significantly increased in SMAD3-/-mice 28 d post-infection compared to both SMAD3+/-mice and to baseline values.This was consistent with more severe colitis development in these animals.CONCLUSION:Data suggest that defects in SMAD3signaling increase susceptibility to H.hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.

  18. National Birth Defects Prevention Study (NBDPS)

    Science.gov (United States)

    ... Heart Defects Atrial Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great ... Defects Fetal Alcohol Syndrome Disorders Gastroschisis Heart Defects Coarctation of the Aorta Hypoplastic left heart syndrome Tetralogy ...

  19. AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

    Directory of Open Access Journals (Sweden)

    Pavankumar Tandra

    2013-11-01

    Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

  20. Lymphocytic adenohypophysitis: skull radiographs and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Saiwai, S.; Miyamoto, T. [Department of Radiology, Kobe Central Municipal Hospital, Hyogo (Japan); Inoue, Y.; Nemoto, Y.; Tashiro, T. [Department of Radiology, Osaka City University Medical School (Japan); Ishihara, T. [Department of Endocrinology, Kobe Central Municipal Hospital, Hyogo (Japan); Matsumoto, S. [Department of Neurosurgery, Kobe Central Municipal Hospital, Hyogo (Japan); Hakuba, A. [Department of Neurosurgery, Osaka City University Medical School, 1-5-7 Asahimachi, Abeno, Osaka, 545 (Japan)

    1998-02-01

    We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass. (orig.) With 3 figs., 1 tab., 40 refs.

  1. Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

    Science.gov (United States)

    Doi, Takuya; Tomonari, Yuki; Kawasako, Kazufumi; Yamada, Naoaki; Tsuchitani, Minoru

    2017-02-04

    Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown.

  2. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors.

  3. Dual character of interaction between lymphocytes and allogeneic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Kochetkova, M.O.; Nikolaeva, I.S.

    1986-10-01

    The mechanisms of stimulation of colony formation by small doses of allogeneic lymphocytes were studied in mice. When interaction of lymphocytes with allogeneic stem cells was studied, bone marrow cells of mice were injected into lethally irradiated recipients in the control, and mixtures of bone marrow cells with varied numbers of lymphocytes were injected in the experiment. Dependence of the inactivation indices on the number of lymphocytes injected, based on the results of counting macro- and microcolonies in the spleen, is shown.

  4. 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.

  5. SnapShot: chronic lymphocytic leukemia.

    Science.gov (United States)

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  6. Regulatory T-lymphocytes in asthma

    NARCIS (Netherlands)

    van Oosterhout, AJM; Bloksma, N

    2005-01-01

    T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. However, little is known about immunoregulatory mechanisms that determine susceptibility to, severity of, or persistence of asthma. The concept of a dist

  7. 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...

  8. 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...

  9. Targeting cytotoxic T lymphocytes for cancer immunotherapy

    OpenAIRE

    Maher, J; Davies, E. T.

    2004-01-01

    In light of their preeminent role in cellular immunity, there is considerable interest in targeting of cytotoxic T-lymphocytes to cancer. This review summarises the active and passive immunotherapeutic approaches under development to achieve this goal, emphasising how recent advances in tumour immunology and gene transfer have impacted upon this field.

  10. 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 develo

  11. Morphometric Characterization of Small Cell Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Chisoi Anca

    2014-11-01

    Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

  12. 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...

  13. 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

    We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58...... 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...... 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...

  14. Rosette formation of pig T lymphocytes with sheep erythrocytes.

    Science.gov (United States)

    Escajadillo, C; Binns, R M

    1975-01-01

    The relationship of sheep RBC rosette formation to density of thymus and blood lymphocytes was investigated. Thymocyte density was unimodal and cells of all densities rosetted equally. Blood lymphocyte density was bimodal with most rosette-forming cells in the denser ficoll layers. Papain treatment of SRBC increases rosette formation with blood lymphocytes while apparently maintaining specificity of T cells.

  15. Blocking Type I Interferon Signaling Rescues Lymphocytes from Oxidative Stress, Exhaustion, and Apoptosis in a Streptozotocin-Induced Mouse Model of Type I Diabetes

    Directory of Open Access Journals (Sweden)

    Hany M. Ibrahim

    2013-01-01

    Full Text Available Elevated levels of type I interferon (IFN during type 1 diabetes mellitus (T1D are associated with a defective immune response. In the present study, we investigated whether blocking type I IFN signaling during streptozotocin- (STZ- induced T1D in mice improves lymphocyte proliferation and escape from continuous apoptosis. Three groups of mice were examined: diabetic mice, type I IFN signaling-incompetent diabetic mice, and control nondiabetic mice. We first found that diabetes induction was accompanied by an elevation in the plasma levels of reactive oxygen species (ROS, hydroperoxide, malondialdehyde (MDN, and the proinflammatory cytokines IL-1α, IL-1β, IL-6, and CXCL10. Blocking type 1 IFN signaling in diabetic mice significantly decreased the levels of oxidative stress and proinflammatory cytokines. In addition, lymphocytes from diabetic mice exhibited a marked reduction in their proliferative capacity, increased apoptosis, upregulation of the exhaustion marker PD-1, and aberrant phosphorylation of STAT1, STAT2, AKT and IκB-α. Interestingly, following the blocking of type I IFN signaling in diabetic mice, the lymphocytes exhibited restored proliferative capacity, decreased apoptosis, normal expression of PD-1, and normal phosphorylation of STAT1, STAT2, AKT and IκB-α. Our data suggest that elevated levels of type I IFN during T1D trigger lymphocyte exhaustion and a defective lymphocyte-medicated immune response.

  16. NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

    OpenAIRE

    Cukic, Vesna

    2016-01-01

    Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surg...

  17. Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

    2008-11-15

    We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

  18. Lymphocyte transformation studies in drug hypersensitivity.

    Science.gov (United States)

    Warrington, R J; Tse, K S

    1979-05-05

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.

  19. Lymphocytic colitis: A clue to bacterial etiology

    Institute of Scientific and Technical Information of China (English)

    Thanaa EA Helal; Naglaa S Ahmed; Osama Abo El Fotoh

    2005-01-01

    AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis.METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain.RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli(14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coliwas associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coliin their biopsy cultures.Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coliin their specimen's culture. None of the controls showed these bacteria in histopathological sections.CONCLUSION: This preliminary study reports an association between E coliand lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coliin the pathogenesis of lymphocytic colitis.

  20. Ventricular Septal Defect (For Parents)

    Science.gov (United States)

    ... Electrocardiogram) Anesthesia - What to Expect Tetralogy of Fallot Coarctation of the Aorta Patent Ductus Arteriosus (PDA) Getting ... Murmurs Atrial Septal Defect Cardiac Catheterization EKG (Video) Coarctation of the Aorta Atrial Septal Defect Ventricular Septal ...

  1. Reconstructions of eyelid defects

    Directory of Open Access Journals (Sweden)

    Nirmala Subramanian

    2011-01-01

    Full Text Available Eyelids are the protective mechanism of the eyes. The upper and lower eyelids have been formed for their specific functions by Nature. The eyelid defects are encountered in congenital anomalies, trauma, and postexcision for neoplasm. The reconstructions should be based on both functional and cosmetic aspects. The knowledge of the basic anatomy of the lids is a must. There are different techniques for reconstructing the upper eyelid, lower eyelid, and medial and lateral canthal areas. Many a times, the defects involve more than one area. For the reconstruction of the lid, the lining should be similar to the conjunctiva, a cover by skin and the middle layer to give firmness and support. It is important to understand the availability of various tissues for reconstruction. One layer should have the vascularity to support the other layer which can be a graft. A proper plan and execution of it is very important.

  2. Wetting on smooth micropatterned defects

    OpenAIRE

    Debuisson, Damien; Dufour, Renaud; Senez, Vincent; Arscott, Steve

    2011-01-01

    We develop a model which predicts the contact angle hysteresis introduced by smooth micropatterned defects. The defects are modeled by a smooth function and the contact angle hysteresis is explained using a tangent line solution. When the liquid micro-meniscus touches both sides of the defect simultaneously, depinning of the contact line occurs. The defects are fabricated using a photoresist and experimental results confirm the model. An important point is that the model is scale-independent,...

  3. 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.

  4. Congenital Heart Defects (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Congenital Heart Defects KidsHealth > For Parents > Congenital Heart Defects A A A What's in this article? How ... a Problem en español Anomalías cardíacas congénitas A congenital heart defect is a problem in the heart's structure that ...

  5. Immunologic studies in two patients with persistent lymphocytic thyroiditis, thyrotoxicosis, and low radioactive iodine uptake

    Energy Technology Data Exchange (ETDEWEB)

    Elliot, I.; Gupta, M.; Hostetter, A.; Sheeler, L.; Skillern, P.; Tubbs, R.

    1984-08-01

    Two patients with persistent lymphocytic thyroiditis and thyrotoxicosis were studied. Both patients presented with severe hyperthyroidism of nine months' duration and had nontender, small thyroid glands. Uptake of radioactive iodine (131I) was consistently low. Serum thyroxine and triiodothyronine levels remained elevated without remission until thyroidectomy. The serum thyroglobulin level was normal, but testing for microsomal antibody gave weakly positive results in one case. Thyroglobulin and thyroid stimulatory antibodies were not found. The ratio of helper to suppressor T cells was elevated in one case. Neither patient showed response to propranolol, prednisone, or iodine. Light microscopic and immunohistologic studies showed severe lymphocytic thyroiditis with formation of secondary lymphoid follicles. Lymphocytes were predominately T cells (OKT11-positive), primarily helper/inducer T cells (OKT4-positive). Hyperplastic nodules contained high immunoreactive thyroglobulin and thyroxine levels. Aberrant thymus was seen within the thyroid. These studies suggest the possibility of intrathyroidal stimulation and hydrolysis of thyroglobulin within thyroid cells and also support the hypothesis that T and B cell immunoregulatory defects are important in the pathogenesis of this disease.

  6. Is lymphocytic (hashimoto) thyroiditis associated with suicide?

    Science.gov (United States)

    Cina, Stephen J; Perper, Joshua A

    2009-09-01

    The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in

  7. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor

    DEFF Research Database (Denmark)

    Geisler, C; Pallesen, G; Platz, P

    1989-01-01

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor....... Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected...... deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue....

  8. Wetting on smooth micropatterned defects

    CERN Document Server

    Debuisson, Damien; Senez, Vincent; Arscott, Steve

    2011-01-01

    We develop a model which predicts the contact angle hysteresis introduced by smooth micropatterned defects. The defects are modeled by a smooth function and the contact angle hysteresis is explained using a tangent line solution. When the liquid micro-meniscus touches both sides of the defect simultaneously, depinning of the contact line occurs. The defects are fabricated using a photoresist and experimental results confirm the model. An important point is that the model is scale-independent, i.e. the contact angle hysteresis is dependent on the aspect ratio of the function, not on its absolute size; this could have implications for natural surface defects.

  9. Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect.

    Science.gov (United States)

    Sala, Pierguido; Colatutto, Antonio; Fabbro, Dora; Mariuzzi, Laura; Marzinotto, Stefania; Toffoletto, Barbara; Perosa, Anna R; Damante, Giuseppe

    2016-04-01

    Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.

  10. Defect Recognition in Thermosonic Imaging

    Institute of Scientific and Technical Information of China (English)

    CHEN Dapeng; WU Naiming; ZHANG Zheng

    2012-01-01

    This work is aimed at developing an effective method for defect recognition in thermosonic imaging.The heat mechanism of thermosonic imaging is introduced,and the problem for defect recognition is discussed.For this purpose,defect existing in the inner wall of a metal pipeline specimen and defects embedded in a carbon fiber reinforced plastic (CFRP) laminate are tested.The experimental data are processed by pulse phase thermography (PPT) method to show the phase images at different frequencies,and the characteristic of phase angle vs frequency curve of thermal anomalies and sound area is analyzed.A binary image,which is based on the characteristic value of defects,is obtained by a new recognition algorithm to show the defects.Results demonstrate good defect recognition performance for thermosonic imaging,and the reliability of this technique can be improved by the method.

  11. Lymphocyte transformation in presumed ocular histoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Ganley, J.P.; Nemo, G.J.; Comstock, G.W.; Brody, J.A.

    1981-08-01

    Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

  12. Bioluminescent assay for human lymphocyte blast transformation.

    Science.gov (United States)

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

    1995-05-01

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

  13. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

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

    2016-01-01

    , and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. DESCRIPTIVE DATA: To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National......, 3,082 patients have been registered. CONCLUSION: The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark......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...

  14. Obinutuzumab for previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Abraham, Jame; Stegner, Mark

    2014-04-01

    Obinutuzumab was approved by the Food and Drug Administration in late 2013 for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). The approval was based on results of an open-label phase 3 trial that showed improved progression-free survival (PFS) with the combination of obinutuzumab plus chlorambucil compared with chlorambucil alone. Obinutuzumab is a monoclonal antibody that targets CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes. After binding to CD20, obinutuzumab mediates B-cell lysis by engaging immune effector cells, directly activating intracellular death signaling pathways, and activating the complement cascade. Immune effector cell activities include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

  15. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  16. Mean dose to lymphocytes during radiotherapy treatments

    Energy Technology Data Exchange (ETDEWEB)

    Brandan, M.E.; Perez-Pastenes, M.A. [Instituto de Fisica (Mexico); Ostrosky-Wegman, P.; Gonsebatt, M.E. [Instituto de Investigaciones Biomedicas (Mexico); Diaz-Perches, R. [Hospital General de Mexico (Mexico)

    1994-10-01

    Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, the authors have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a {sup 60}Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model. 10 refs., 3 figs., 2 tabs.

  17. Metabolism pathways in chronic lymphocytic leukemia.

    Science.gov (United States)

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

    2016-01-01

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

  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. B cell acute lymphocytic leukemia in pregnancy.

    Science.gov (United States)

    Bottsford-Miller, Justin; Haeri, Sina; Baker, Arthur M; Boles, Jeremiah; Brown, Mark

    2011-08-01

    Acute lymphocytic leukemia (ALL) is a rare occurrence in pregnancy and can be rapidly fatal if left untreated. The need for immediate treatment of ALL, coupled with the maternal-fetal risks from the chemotherapy regimen render a therapeutic dilemma in pregnant women with ALL. We report a case of ALL diagnosed in the 24th week of pregnancy to outline our management strategy, to demonstrate the feasibility of treatment with multi-agent chemotherapy, and to provide a review of the literature.

  20. Sudden unexpected death associated with lymphocytic thyroiditis.

    Science.gov (United States)

    Vestergaard, Vibeke; Drostrup, Dorthe Høj; Thomsen, Jørgen L

    2007-04-01

    A forensic autopsy study comprising 125 cases was carried out retrospectively in order to evaluate pathological changes in the thyroid gland in different groups of death. The five groups selected consecutively were: (i) opiate addicts who died from an overdose, (ii) alcoholics who died as a result of their alcohol abuse, (iii) cases of fatal poisoning other than opiate addicts, (iv) unknown cause of death and (v) controls without prior disease. Tissue samples from the thyroid gland were cut and stained with haematoxylin and eosin and van Gieson. Histology examinations were subsequently performed blind with semiquantitative assessment of the following six parameters: (a) height of the follicular epithelium, (b) the amount of lymphocytes, (c) the presence of plasma cells, (d) hyperplastic follicular changes, (e) oxyphilic changes, and (f) fibrosis. The most striking result was the finding of extensive lymphocytic infiltration of the thyroid parenchyma in five of the 124 cases, of which four belonged in the group of 'unknown cause of death'. This discovery leads to reflections regarding lymphocytic thyroiditis as a cause of death, either by itself or in combination with other disorders. Silent (painless) thyroiditis, especially, is easily overlooked at autopsy as there are no macroscopic changes and often no prior symptoms or history of thyroid disease pointing towards this condition. Analyses of thyroid hormones are unreliable in predicting endocrine status in life. Routine microscopy of the thyroid gland is therefore advocated in cases of sudden unexpected death in order to diagnose thyroid disease, in particular silent (painless) thyroiditis.

  1. 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.

  2. [Circadian rhythm of human lymphocyte subpopulations].

    Science.gov (United States)

    Pasqualetti, P; Colantonio, D; Casale, R; Colangeli, S; Natali, G

    1988-01-01

    Circadian rhythm of lymphocyte subsets was investigated in four healthy subjects, males, aged 35-58 years old. After a period of ambiental synchronization, venous blood samples were taken during a span of a day at 0.00 a.m., 4.00 a.m., 8.00 a.m., noon, 4.00 p.m. and 8.00 p.m. Lymphocyte subsets (OKT3, OKT4, OKT8, OKB7, OKJa1) were determined by monoclonal antibodies method, and serum level of cortisol by radioimmunoassay method. The OKT4/OKT8 ratio was also calculated. Data were analyzed by chronograms (mean +/- 1SD) and by cosinor method. Results show a significant circadian rhythm for each lymphocyte subset and for serum cortisol levels. The lowest levels of all circulating subsets were seen between noon and 4.00 p.m. and the highest levels around midnight, inversely related with the circadian rhythm of serum cortisol. The OKT4/OKT8 ratio, on the contrary, was relatively constant during the day, without a significant circadian rhythm. These observations have laboratoristic, clinical, and therapeutic implications and should be considered in the course of immunological studies.

  3. Lymphocytic hypophysitis masquerading as pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Rajneesh Mittal

    2012-01-01

    Full Text Available Introduction: Pituitary hypophysitis (PH is characterized by pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be autoimmune or secondary to systemic diseases or infections. Based on the histopathological findings PH is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous, necrotizing and Immunoglobulin- G4 (IgG4 plasmacytic types. Objective: To report a case of lymphocytic hypophysitis (LH. Case Report: A 15-year-old girl presented with history of headache, amenorrhea, and history of polyuria for past 4 months. Initial evaluation had suppressed follicular stimulating hormone (<0.01 mIU/ml, high prolactin levels (110.85 ng/ml and diabetes insipidus (DI. Magnetic resonance imaging of sella was suggestive of pituitary macroadenoma with partial compression over optic chiasma. Patient underwent surgical decompression. Yellowish firm tissue was evacuated and xanthochromic fluid was aspirated. Histopathology was suggestive of LH. She resumed her cycles postoperatively after 4 months, prolactin levels normalized, however, she continues to have DI and is on desmopressin spray. This case has been presented here for its rare presentation in an adolescent girl because it is mostly seen in young females and postpartum period and its unique presentation as an expanding pituitary mass with optic chiasma compression. Conclusion: Definitive diagnosis of LH is based on histopathological evaluation. Therapeutic approach should be based on the grade of suspicion and clinical manifestations of LH.

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

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

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

  5. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  6. Suppression of viral infectivity through lethal defection

    Science.gov (United States)

    Grande-Pérez, Ana; Lázaro, Ester; Lowenstein, Pedro; Domingo, Esteban; Manrubia, Susanna C.

    2005-01-01

    RNA viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. Viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. An alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mutagens. Here, we report about persistent infections of lymphocytic choriomeningitis virus treated with fluorouracil, where a progressive debilitation of infectivity leading to eventual extinction occurs. The transition to extinction is accompanied by the production of large amounts of RNA, indicating that the replicative ability of the quasispecies is not strongly impaired by the mutagen. By means of experimental and theoretical approaches, we propose that a fraction of the RNA molecules synthesized can behave as a defective subpopulation able to drive the viable class extinct. Our results lead to the identification of two extinction pathways, one at high amounts of mutagen, where the quasispecies completely loses its ability to infect and replicate, and a second one, at lower amounts of mutagen, where replication continues while the infective class gets extinct because of the action of defectors. The results bear on a potential application of increased mutagenesis as an antiviral strategy in that low doses of a mutagenic agent may suffice to drive persistent virus to extinction. PMID:15767582

  7. Dipole defects in beryl

    Energy Technology Data Exchange (ETDEWEB)

    Holanda, B A; Cordeiro, R C; Blak, A R, E-mail: bruna.holanda@usp.br, E-mail: renan.cordeiro@usp.br, E-mail: anablak@if.usp.br

    2010-11-15

    Dipole defects in gamma irradiated and thermally treated beryl (Be{sub 3}Al{sub 2}Si{sub 6}O{sub 18}) samples have been studied using the Thermally Stimulated Depolarization Currents (TSDC) technique. TSDC experiments were performed in pink (morganite), green (emerald), blue (aquamarine) and colourless (goshenite) natural beryl. TSDC spectra present dipole peaks at 190K, 220K, 280K and 310K that change after gamma irradiation and thermal treatments. In morganite samples, for thermal treatments between 700K and 1100K, the 280K peak increase in intensity and the band at 220K disappears. An increase of the 280K peak and a decrease of the 190K peak were observed in the TSDC spectra of morganite after a gamma irradiation of 25kGy performed after the thermal treatments. In the case of emerald samples, thermal treatments enhanced the 280K peak and gamma irradiation partially destroyed this band. The goshenite TSDC spectra present only one band at 280K that is not affected either by thermal treatments or by gamma irradiation. All the observed peaks are of dipolar origin because the intensity of the bands is linearly dependent on the polarization field, behaviour of dipole defects. The systematic study, by means of TSDC measurements, of ionizing irradiation effects and thermal treatments in these crystals makes possible a better understanding of the role played by the impurities in beryl crystals.

  8. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma.

  9. Suppressive effects of antigens on the activity of specific activated lymphocytes: A test to define the specificity of activated lymphocytes

    Institute of Scientific and Technical Information of China (English)

    HU Jun; PAN Sheng-jun; CAI Zhen-jie; GUAN De-lin; LIU Xiao-cheng

    2006-01-01

    Objective:With the regular mixed lymphocytes culture (MLC) to detect the allograft rejection, the reactivity of the activated lymphocytes (primed lymphocytes) of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor's HLA antigens in the recipient's peripheral blood. Methods: Anti-IL-2 neutralizing monoclonal antibody (anti-IL-2 N-mAb) and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results: When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection.Conclusion :It suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.

  10. Defects in new protective aprons

    Energy Technology Data Exchange (ETDEWEB)

    Glaze, S.; LeBlanc, A.D.; Bushong, S.C.

    1984-07-01

    Upon careful examination, several defects have been detected in new protective aprons. The nature of the defects is identified and described. Although the occurrence of such defects has not exceeded 5%, they are significant enough to warrant return of the lead apron to the supplier. It is recommended that the integrity of all new protective aprons be verified upon receipt as well as at yearly intervals.

  11. The association between chronic lymphocytic thyroiditis and thyroid tumors.

    Science.gov (United States)

    Tamimi, Dalal M

    2002-04-01

    An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.

  12. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    Science.gov (United States)

    2017-01-24

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  13. Studies of defects and defect agglomerates by positron annihilation spectroscopy

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Singh, B.N.

    1997-01-01

    and with other experimental methods (in particular transmission electron microscopy) forms the basis for the use of PAS to quantitatively characterize defects and defect complexes, both visible and invisible is transmission electron microscopes: this is illustrated by some examples. Finally, the advantages...

  14. Chronic lymphocytic leukemia: case-based session.

    Science.gov (United States)

    Rai, K R; Döhner, H; Keating, M J; Montserrat, E

    2001-01-01

    Drs. Hartmut Döhner, Michael J. Keating, Kanti R. Rai and Emili Montserrat form the panel to review chronic lymphocytic leukemia (CLL) while focusing on the clinical features of a particular patient. The pace of progress in CLL has accelerated in the past decade. The pathophysiological nature of this disease, as had been known in the past, was based largely on the intuitive and empiric notions of two leaders in hematology, William Dameshek and David Galton. Now the works of a new generation of leaders are providing us with the scientific explanations of why CLL is a heterogeneous disease, perhaps consisting of at least two separate entities. In one form of CLL, the leukemic lymphocytes have a surface immunoglobulin (Ig) variable region gene that has undergone somatic mutations, with tell-tale markers suggesting that these cells had previously traversed the germinal centers. Such patients have a distinctly superior prognosis than their counterparts whose leukemic lymphocytes IgV genes have no mutations (these are indeed immunologically naive cells), who have a worse prognosis. The introduction of fluorescence in situ hybridization (FISH) technique has provided us with new insights into the diverse chromosomal abnormalities that can occur in CLL, and which have significant impact on the clinical behavior and prognosis of patients with this disease. Major advances in therapeutics of CLL also have occurred during the past decade. Two monoclonal antibodies, Campath-1H (anti-CD52) and rituximab (anti-CD20), and one nucleoside analogue, fludarabine, have emerged as three agents of most promise in the front-line treatment of this disease. Studies currently in progress reflect our attempts to find the most effective manner of combining these agents to improve the overall survival statistics for CLL patients. As in many other hematological malignancies, high dose chemotherapy followed by autologous or HLA-compatible allogeneic stem cells rescue strategies are under study as

  15. Phenotypic and Functional Analysis of Porcine T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    李华; 陈应华

    2001-01-01

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

  16. Background Defect Density Reduction Using Automated Defect Inspection And Analysis

    Science.gov (United States)

    Weirauch, Steven C.

    1988-01-01

    Yield maintenance and improvement is a major area of concern in any integrated circuit manufacturing operation. A major aspect of this concern is controlling and reducing defect density. Obviously, large defect excursions must be immediately addressed in order to maintain yield levels. However, to enhance yields, the subtle defect mechanisms must be reduced or eliminated as well. In-line process control inspections are effective for detecting large variations in the defect density on a real time basis. Examples of in-line inspection strategies include after develop or after etch inspections. They are usually effective for detecting when a particular process segment has gone out of control. However, when a process is running normally, there exists a background defect density that is generally not resolved by in-line process control inspections. The inspection strategies that are frequently used to monitor the background defect density are offline inspections. Offline inspections are used to identify the magnitude and characteristics of the background defect density. These inspections sample larger areas of product wafers than the in-line inspections to allow identification of the defect generating mechanisms that normally occur in the process. They are used to construct a database over a period of time so that trends may be studied. This information enables engineering efforts to be focused on the mechanisms that have the greatest impact on device yield. Once trouble spots in the process are identified, the data base supplies the information needed to isolate and solve them. The key aspect to the entire program is to utilize a reliable data gathering mechanism coupled with a flexible information processing system. This paper describes one method of reducing the background defect density using automated wafer inspection and analysis. The tools used in this evaluation were the KLA 2020 Wafer Inspector, KLA Utility Terminal (KLAUT), and a new software package developed

  17. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  18. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K

    1986-01-01

    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR...

  19. Blocking Type I Interferon Signaling Rescues Lymphocytes from Oxidative Stress, Exhaustion, and Apoptosis in a Streptozotocin-Induced Mouse Model of Type I Diabetes

    OpenAIRE

    Ibrahim, Hany M.; El-Elaimy, Ibrahim A.; Saad Eldien, Heba M.; Badr Mohamed Badr; Rabah, Danny M.; Gamal Badr

    2013-01-01

    Elevated levels of type I interferon (IFN) during type 1 diabetes mellitus (T1D) are associated with a defective immune response. In the present study, we investigated whether blocking type I IFN signaling during streptozotocin- (STZ-) induced T1D in mice improves lymphocyte proliferation and escape from continuous apoptosis. Three groups of mice were examined: diabetic mice, type I IFN signaling-incompetent diabetic mice, and control nondiabetic mice. We first found that diabetes induction w...

  20. Irradiation Defects in Silicon Crystal

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The application of irradiation in silicon crystal is introduced.The defects caused by irradiation are reviewed and some major ways of studying defects in irradiated silicon are summarized.Furthermore the problems in the investigation of irradiated silicon are discussed as well as its properties.

  1. Facts about Atrial Septal Defect

    Science.gov (United States)

    ... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For... Media Policy Makers Facts about Atrial Septal Defect Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  2. Facts about Ventricular Septal Defect

    Science.gov (United States)

    ... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For... Media Policy Makers Facts about Ventricular Septal Defect Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  3. Birth Defects Research and Tracking

    Science.gov (United States)

    ... used data from the National Birth Defects Prevention Study (NBDPS) to examine maternal asthma medication use during pregnancy and the risk of certain birth defects. (Published October 22, 2014) World Down Syndrome Day Read one mother’s reflection on the birth ...

  4. Holographic Chern-Simons Defects

    CERN Document Server

    Fujita, Mitsutoshi; Meyer, Rene; Sugimoto, Shigeki

    2016-01-01

    We study SU(N) Yang-Mills-Chern-Simons theory in the presence of defects that shift the Chern-Simons level from a holographic point of view by embedding the system in string theory. The model is a D3-D7 system in Type IIB string theory, whose gravity dual is given by the AdS soliton background with probe D7-branes attaching to the AdS boundary along the defects. We holographically renormalize the free energy of the defect system with sources, from which we obtain the correlation functions for certain operators naturally associated to these defects. We find interesting phase transitions when the separation of the defects as well as the temperature are varied. We also discuss some implications for the Fractional Quantum Hall Effect and for two-dimensional QCD.

  5. Spondylarthritis in the absence of B lymphocytes.

    Science.gov (United States)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P

    2008-03-01

    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.

  6. Benzene metabolites induce apoptosis in lymphocytes.

    Science.gov (United States)

    Martínez-Velázquez, M; Maldonado, V; Ortega, A; Meléndez-Zajgla, J; Albores, A

    2006-08-01

    Benzene is an important environmental pollutant with important health implications. Exposure to this aromatic hydrocarbon is associated with hematotoxicity, and bone marrow carcinogenic effects. It has been shown that benzene induces oxidative stress, cell cycle alterations, and programmed cell death in cultured cells. Hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. Nevertheless, there are no reports on the cellular effects of reactive intermediates derived from hepatic metabolism of benzene. Thus, the goal of this project was to determine the cellular alterations of benzene metabolites produced by the cultured hepatic cell line HepG2. Supernatants collected from these cells were applied to a culture of freshly isolated lymphocytes. A higher decrease in cell viability was found in cells exposed to these supernatants than to unmetabolized benzene. This viability decrease was due to apoptosis, as determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay and internucleosomal fragmentation of DNA. When supernatants were analyzed by HPLC, we found that not all the hydrocarbon was biotransformed, since a 28 microM concentration (37%) remained. The only metabolite found in the culture medium was muconic acid. The present results show that muconic acid derived from benzene metabolism is able to cooperate with the pollutant for the induction of apoptosis in rat lymphocytes.

  7. Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rogers, Kerry A; Woyach, Jennifer A

    2016-04-01

    Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias.

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

    DEFF Research Database (Denmark)

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

    1987-01-01

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

  9. Lymphocytes and liver fibrosis in HIV & HCV coinfection

    NARCIS (Netherlands)

    Feuth, M.

    2014-01-01

    Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat

  10. Polycyclic’ Aromatic Hydrocarbon Induced Intracellular Signaling and Lymphocyte Apoptosis

    DEFF Research Database (Denmark)

    Schneider, Alexander M.

    lymphocytes. Our experiments on preB lymphocytes supported by stromal cells suggest that apoptosis is one of the mechanisms for PAH immunosuppression. It could be either due to direct effect of the PAH on the B cells, via stromal cell signaling. Ubiquitous PAH-like toxin, fluoranthene, was tested for it...

  11. Effect of praziquantel on human lymphocyte proliferation in vitro

    DEFF Research Database (Denmark)

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

    1984-01-01

    The antischistosomal drugs tartar emetic and niridazole exert immunosuppression both in vitro and in vivo. In the present study the influence of praziquantel (Biltricide), a potent schistosomicidal drug, on human lymphocyte proliferation in vitro was investigated. Praziquantel 80 micrograms...... no suppressive effect on human lymphocyte proliferation in vitro....

  12. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P;

    1989-01-01

    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control do...

  13. Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

    NARCIS (Netherlands)

    Ramanauskaite, R B; SegersNolten, IGMJ; DeGrauw, K J; Sijtsema, N M; VanderMaas, L; Greve, J; Otto, C; Figdor, C G

    1997-01-01

    Carotenoid levels in lymphocytes obtained from peripheral blood of healthy people have been investigated by Raman microspectroscopy. We observed that carotenoids are concentrated in so-called ''Gall bodies''. The level of carotenoids in living human lymphocytes was found to be age-dependent and to d

  14. 9 CFR 113.42 - Detection of lymphocytic choriomeningitis contamination.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Detection of lymphocytic choriomeningitis contamination. 113.42 Section 113.42 Animals and Animal Products ANIMAL AND PLANT HEALTH... contamination. The test for detection of lymphocytic choriomeningitis (LCM) virus provided in this section...

  15. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...

  16. Endothelial PI 3-kinase activity regulates lymphocyte diapedesis.

    Science.gov (United States)

    Nakhaei-Nejad, Maryam; Hussain, Amer M; Zhang, Qiu-Xia; Murray, Allan G

    2007-12-01

    Lymphocyte recruitment to sites of inflammation involves a bidirectional series of cues between the endothelial cell (EC) and the leukocyte that culminate in lymphocyte migration into the tissue. Remodeling of the EC F-actin cytoskeleton has been observed after leukocyte adhesion, but the signals to the EC remain poorly defined. We studied the dependence of peripheral blood lymphocyte transendothelial migration (TEM) through an EC monolayer in vitro on EC phosphatidylinositol 3-kinase (PI 3-kinase) activity. Lymphocytes were perfused over cytokine-activated EC using a parallel-plate laminar flow chamber. Inhibition of EC PI 3-kinase activity using LY-294002 or wortmannin decreased lymphocyte TEM (48 +/- 6 or 34 +/- 7%, respectively, vs. control; mean +/- SE; P structure" after intercellular adhesion molecule-1 ligation, whereas this was inhibited by jasplakinolide treatment. A similar fraction of lymphocytes migrated on control or LY-294002-treated EC and localized to interendothelial junctions. However, lymphocytes failed to extend processes below the level of vascular endothelial (VE)-cadherin on LY-294002-treated EC. Together these observations indicate that EC PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier.

  17. Software Defect Detection with Rocus

    Institute of Scientific and Technical Information of China (English)

    Yuan Jiang; Ming Li; Zhi-Hua Zhou

    2011-01-01

    Software defect detection aims to automatically identify defective software modules for efficient software test in order to improve the quality of a software system. Although many machine learning methods have been successfully applied to the task, most of them fail to consider two practical yet important issues in software defect detection. First, it is rather difficult to collect a large amount of labeled training data for learning a well-performing model; second, in a software system there are usually much fewer defective modules than defect-free modules, so learning would have to be conducted over an imbalanced data set. In this paper, we address these two practical issues simultaneously by proposing a novel semi-supervised learning approach named Rocus. This method exploits the abundant unlabeled examples to improve the detection accuracy, as well as employs under-sampling to tackle the class-imbalance problem in the learning process. Experimental results of real-world software defect detection tasks show that Rocgs is effective for software defect detection. Its performance is better than a semi-supervised learning method that ignores the class-imbalance nature of the task and a class-imbalance learning method that does not make effective use of unlabeled data.

  18. 2010 Defects in Semiconductors GRC

    Energy Technology Data Exchange (ETDEWEB)

    Shengbai Zhang

    2011-01-06

    Continuing its tradition of excellence, this Gordon Conference will focus on research at the forefront of the field of defects in semiconductors. The conference will have a strong emphasis on the control of defects during growth and processing, as well as an emphasis on the development of novel defect detection methods and first-principles defect theories. Electronic, magnetic, and optical properties of bulk, thin film, and nanoscale semiconductors will be discussed in detail. In contrast to many conferences, which tend to focus on specific semiconductors, this conference will deal with point and extended defects in a broad range of electronic materials. This approach has proved to be extremely fruitful for advancing fundamental understanding in emerging materials such as wide-band-gap semiconductors, oxides, sp{sup 2} carbon based-materials, and photovoltaic/solar cell materials, and in understanding important defect phenomena such as doping bottleneck in nanostructures and the diffusion of defects and impurities. The program consists of about twenty invited talks and a number of contributed poster sessions. The emphasis should be on work which has yet to be published. The large amount of discussion time provides an ideal forum for dealing with topics that are new and/or controversial.

  19. Lymphocytes in patients with psoriasis promote proliferation of keratinocytes

    Institute of Scientific and Technical Information of China (English)

    DENG An-mei; ZHONG Ren-qian; CHEN Sun-xiao; ZHOU Ye; KONG Xian-tao

    2002-01-01

    Objective: To analyze the effect of lymphocytes on proliferation of keratinocytes in patients with psoriasis. Methods: Lymphocytes in lesion and peripheral blood were isolated and amplified, then cultured together with normal keratinocytes. By MTT method, the living cells were quantified in the mixed culture.Results: Compared with normal controls, lymphocytes from lesion and peripheral blood of psoriasis both promote the proliferation of keratinocytes (P<0. 01 and P<0. 05 respectively). The concentrations of IL-2 and IFN-γ in the mixture of lesion lymphocytes and keratinocytes were significantly higher than that of controls.Tripterygium glycosides inhibited this promotion. Conclusion: Lymphocytes in patients with psoriasis (mainly Thl cell) play an important role in proliferation of keratinocytes. This psoriasis cell model is useful for studies on signal transduction in psoriasis.

  20. DEFECTS SIMULATION OF ROLLING STRIP

    Directory of Open Access Journals (Sweden)

    Rudolf Mišičko

    2009-06-01

    Full Text Available The defects in the continuous casting slabs can be developed or kept down in principle by rolling technology, especially depend to sort, size and distribution of primary defects, as well as used of rolling parameters. Scope of the article is on observation behavior artificial surface and undersurface defects (scores without filler (surface defects and filling by oxides and casting powder (subsurface defects. First phase of hot rolling process have been done by software simulation DEFORM 3D setting to the limited condition for samples with surface defects. Samples of material with low-carbon steel of sizes h x b x l have been chosen and the surface defects shape „U” and „V” of scores have been injected artificially by software. The process of rolling have been simulated on the deformation temperatures 1200°C and 900°C, whereas on the both of this deformation temperatures have been applied amount of deformation 10 and 50 %. With respect to the process of computer simulation, it is not possible to truthful real oxidation condition (physical – chemical process during heat of metal, in the second phase of our investigation have been observed influence of oxides and casting powders inside the scores for a defect behavior in plastic deformation process (hot and cold rolling process in laboratory condition. The basic material was STN steel class 11 375, cladding material was steel on the bases C-Mn-Nb-V. Scores have been filled by scales to get from the heating temperatures (1100°C a 1250°C, varied types of casting powders, if you like mixture of scale and casting powders in the rate 1:4. The joint of the basic and cladding material have been done by peripheral welded joint. Experiment results from both phases are pointed on the evolution of original typology defects in rolling process.

  1. Lymphocyte respiration in children with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Aburawi Elhadi H

    2012-12-01

    Full Text Available Abstract Background This study measured lymphocyte mitochondrial O2 consumption (cellular respiration in children with trisomy 21. Methods Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O2] was determined as a function of time from the phosphorescence decay rates (1/τ of Pd (II-meso-tetra-(4-sulfonatophenyl-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O2] declined linearly with time, confirming the zero-order kinetics of O2 conversion to H2O by cytochrome oxidase. The rate of respiration (k, in μM O2 min-1, thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. Results For control children (age = 8.8 ± 5.6 years, n = 26, the mean (± SD value of kc (in μM O2 per min per 107 cells was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61. For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26, the values of kc were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80, pp6.1 mU/L. Fourteen of 26 (54% children with trisomy 21 had kc values of 0.20 to 0.60 (i.e., kc positively correlated with body-mass index (BMI, R >0.302, serum creatinine (R >0.507, blood urea nitrogen (BUN, R >0.535 and albumin (R >0.446. Conclusions Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.

  2. Early interferon-γ production in human lymphocyte subsets in response to nontyphoidal Salmonella demonstrates inherent capacity in innate cells.

    Directory of Open Access Journals (Sweden)

    Tonney S Nyirenda

    Full Text Available BACKGROUND: Nontyphoidal Salmonellae frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with Salmonella that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in Salmonella infection. METHODOLOGY: Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to Salmonella (as evidence of immunity to Salmonella, in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of Salmonella Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined. PRINCIPAL FINDINGS: Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test, P<0.001 and ≤0.02 for each innate subset compared, respectively, with CD4(+- and CD8(+-T cells. The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria (P<0.0001. CONCLUSION/SIGNIFICANCE: Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to Salmonella infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody

  3. Expression of protooncogenes during lymphocyte activation by growth factors.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  5. Five Facts about Congenital Heart Defects

    Science.gov (United States)

    ... Button Past Emails CDC Features Five Facts about Congenital Heart Defects Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Congenital heart defects are the most common types of birth defects. ...

  6. Mediastinal irradiation for chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Sawitskii, A.; Rai, K.R.; Aral, I.; Silver, R.T.; Glicksman, A.S.; Carey, R.W.; Scialla, S.; Cornell, C.J. Jr.; Seligman, B.; Shapiro, L.

    1976-12-01

    Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 percent, but the duration of response was short. The response rate was 77 percent for the patients receiving a total radiation dose greater than 3,000 rads and 45 percent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated with the severity of reaction or death.

  7. Role of angiogenesis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Letilovic, Tomislav; Vrhovac, Radovan; Verstovsek, Srdan; Jaksic, Branimir; Ferrajoli, Alessandra

    2006-09-01

    Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently. An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications.

  8. Chronic lymphocytic leukemia in African Americans.

    Science.gov (United States)

    Coombs, Catherine C; Falchi, Lorenzo; Weinberg, J Brice; Ferrajoli, Alessandra; Lanasa, Mark C

    2012-11-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States with almost 4390 attributable deaths per year. Epidemiologic data compiled by the Surveillance, Epidemiology and End Results (SEER) program identifies important differences in incidence and survival for African Americans with CLL. Although the incidence of CLL is lower among African Americans than among Caucasians (4.6 and 6.2 per 100 000 men, respectively), age-adjusted survival is inferior. African American patients with CLL are almost twice as likely to die from a CLL-related complication in the first 5 years after diagnosis as are Caucasian patients with CLL. The biologic basis for these observations is almost entirely unexplored, and a comprehensive clinical analysis of African American patients with CLL is lacking. This is the subject of the present review.

  9. Thyroid carcinoma: immunology, irradiation, and lymphocytic infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Shull, J.H.; Sharon, N.; Victor, T.A.; Scanlon, E.F.

    1979-06-01

    Patients undergoing thyroidectomies at Evanston (I11) Hospital, during a six-month period had immunological studies performed preoperatively. No differential could be found between those with carcinoma or benign pathologic findings. T- and B-cell distribution and lymphocytic response to mitogens varied widely. Quantitative immunoglobulins showed slightly increased levels of IgG in patients wih carcinoma and thyroiditis in comparison with those patients with adenomas. Antithyroglobulin antibodies were negative in all patients. Pathology slides from 107 patients with thyroid carcinoma between 1972 and 1978 at Evanston Hospital were reviewed for the presence of thyroiditis, either focal or diffuse. It was found that 50% of all carcinomas had either diffuse or focal thyroiditis. Diffuse thyroiditis was more common in patients with no history of irradiation and papillary carcinoma, and in younger age groups.

  10. Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Zusen Fan; Qixiang Zhang

    2005-01-01

    Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell.The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

  11. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  12. Epigenetic repolarization of T lymphocytes from chronic lymphocytic leukemia patients using 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Dubovsky, Jason A; Powers, John J; Gao, Yang; Mariusso, Luis F; Sotomayor, Eduardo M; Pinilla-Ibarz, Javier A

    2011-09-01

    T cell immune dysfunction has an important role in the profound immune suppression that characterizes chronic lymphocytic leukemia (CLL). Improper polarization of T cells has been proposed as one of the mechanism involved. Mounting data implicates chromatin regulation, namely promoter methylation, in the plasticity of naïve human T cells. Recent in vitro evidence indicates that this plasticity may be phenotypically altered by using methylation inhibitors which are approved for clinical use in certain types of cancer. These results beg the question: can the ineffective polarization of T lymphocytes in the context of CLL be effectively modulated using methylation inhibitors in a sustainable therapeutic fashion? To answer this question our laboratory has studied the effects of 5-aza-2'-deoxycytidine (5A2) in helper and cytotoxic T lymphocytes from healthy donors and CLL patients in well characterized molecular and epigenetic signaling pathways involved in effective polarization. Moreover, we sought to investigate the consequences of methylation inhibitor treatment on lymphocyte survival, activation intensity, and naïve cell polarization. Our data indicates that 5A2 treatment can depolarize Th2 cells to effectively secrete interferon gamma, signal via T-bet, and achieve demethylation of critical Th1 specific promoters. Moreover, we demonstrate that 5A2 can force Th1 polarization of naïve T cells despite a strong IL-4 stimuli and a lack of IL-12. In conclusion our data seeks to define a modality in which improper or ineffective T cell polarization can be altered by 5AZA and could be incorporated in future therapeutic interventions.

  13. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection.

    Science.gov (United States)

    Yamada, Noriyuki; Oizumi, Satoshi; Kikuchi, Eiki; Shinagawa, Naofumi; Konishi-Sakakibara, Jun; Ishimine, Atsushi; Aoe, Keisuke; Gemba, Kenichi; Kishimoto, Takumi; Torigoe, Toshihiko; Nishimura, Masaharu

    2010-10-01

    Defects in human leukocyte antigen (HLA) class I expression may allow tumor cells to escape immune recognition. T cell infiltration is associated with a good prognosis in many cancers. However, the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM) has not been fully analyzed. In the present study, we investigated the immune profiles and conducted outcome analyses of MPM patients. HLA class I expression and TILs (CD4(+), CD8(+), and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. The expression of HLA class I was positive in all patients. There was no case that showed negative HLA class I expression. The density of CD4(+) and CD8(+) TILs were strongly correlated (R = 0.76, p < 0.001). A high density of CD8(+) TILs was a significantly better prognostic factor for the survival of patients with extrapleural pneumonectomy (p < 0.05). Multivariate analysis revealed that a high density of CD8(+) TILs is an independent prognostic factor for patients who underwent extrapleural pneumonectomy. The presence of intratumoral CD8(+) T cells was correlated with an improved clinical outcome, raising the possibility that CD8(+) T cells might play a pivotal role in the antitumor immune response against MPMs. Thus, the stimulation of CD8(+) lymphocytes might be an efficacious immunotherapy for MPM patients.

  14. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  15. Lymphocytes subsets in children with febrile convulsions.

    Science.gov (United States)

    Tuncer, Oğuz; Karaman, Sait; Caksen, Hüseyin; Oner, Ahmet Faik; Odabas, Dursun; Yilmaz, Cahide; Atas, Bülent

    2007-07-01

    In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p .05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.

  16. Ventricular Septal Defect (For Teens)

    Science.gov (United States)

    ... upper filling chambers are the atria . In normal circulation, blood that returns from the body to the ... Causes a VSD? Ventricular septal defects occur during fetal heart development and are present at birth. During ...

  17. Painless causality in defect calculations

    CERN Document Server

    Cheung, C; Cheung, Charlotte; Magueijo, Joao

    1997-01-01

    Topological defects must respect causality, a statement leading to restrictive constraints on the power spectrum of the total cosmological perturbations they induce. Causality constraints have for long been known to require the presence of an under-density in the surrounding matter compensating the defect network on large scales. This so-called compensation can never be neglected and significantly complicates calculations in defect scenarios, eg. computing cosmic microwave background fluctuations. A quick and dirty way to implement the compensation are the so-called compensation fudge factors. Here we derive the complete photon-baryon-CDM backreaction effects in defect scenarios. The fudge factor comes out as an algebraic identity and so we drop the negative qualifier ``fudge''. The compensation scale is computed and physically interpreted. Secondary backreaction effects exist, and neglecting them constitutes the well-defined approximation scheme within which one should consider compensation factor calculatio...

  18. Atrial Septal Defect (For Teens)

    Science.gov (United States)

    ... septal defect (pronounced: AY-tree-ul SEP-tul DEE-fekt), or ASD for short, is sometimes referred ... can be treated with cardiac catheterization (pronounced: CAR-dee-ack cath-uh-turr-ih-ZAY-shun), in ...

  19. Congenital heart defect - corrective surgery

    Science.gov (United States)

    ... Hypoplastic left heart repair; Tetralogy of Fallot repair; Coarctation of the aorta repair; Atrial septal defect repair; ... done in the neonatal intensive care unit (NICU). Coarctation of the aorta repair: Coarctation of the aorta ...

  20. Defective Autophagy Initiates Malignant Transformation.

    Science.gov (United States)

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kroemer, Guido

    2016-05-19

    In this issue of Molecular Cell, Park et al. (2016) elegantly demonstrate that a partial defect in autophagy supports malignant transformation as it favors the production of genotoxic reactive oxygen species by mitochondria.

  1. Down-regulation of the interferon signaling pathway in T lymphocytes from patients with metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Rebecca J Critchley-Thorne

    2007-05-01

    Full Text Available BACKGROUND: Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. METHODS AND FINDINGS: To gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were compared to 12 healthy controls. Of 25 significantly altered genes in T cells and B cells from melanoma patients, 17 are interferon (IFN-stimulated genes. These microarray findings were further confirmed by quantitative PCR and functional responses to IFNs. The median percentage of lymphocytes that phosphorylate STAT1 in response to interferon-alpha was significantly reduced (Delta = 16.8%; 95% confidence interval, 0.98% to 33.35% in melanoma patients (n = 9 compared to healthy controls (n = 9 in Phosflow analysis. The Phosflow results also identified two subgroups of patients with melanoma: IFN-responsive (33% and low-IFN-response (66%. The defect in IFN signaling in the melanoma patient group as a whole was partially overcome at the level of expression of IFN-stimulated genes by prolonged stimulation with the high concentration of IFN-alpha that is achievable only in IFN therapy used in melanoma. The lowest responders to IFN-alpha in the Phosflow assay also showed the lowest gene expression in response to IFN-alpha. Finally, T cells from low-IFN-response patients exhibited functional abnormalities, including decreased expression of activation markers CD69, CD25, and CD71; TH1 cytokines interleukin-2, IFN-gamma, and tumor necrosis factor alpha, and reduced survival following stimulation with anti-CD3/CD28 antibodies compared to controls. CONCLUSIONS: Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to

  2. Stable line defects in silicene

    Science.gov (United States)

    Ghosh, Dibyajyoti; Parida, Prakash; Pati, Swapan K.

    2015-11-01

    Line defects in two-dimensional (2D) materials greatly modulate various properties of their pristine form. Using ab initio molecular dynamics (AIMD) simulations, we investigate the structural reconstructions of different kinds of grain boundaries in the silicene sheets. It is evident that depending upon the presence of silicon adatoms and edge shape of grain boundaries (i.e., armchair or zigzag), stable extended line defects (ELDs) can be introduced in a controlled way. Further studies show the stability of these line-defects in silicene, grown on Ag(111) surface at room-temperature. Importantly, unlike most of the 2D sheet materials such as graphene and hexagonal boron nitride, 5-5-8 line defects modify the nonmagnetic semimetallic pristine silicene sheet to spin-polarized metal. As ferromagnetically ordered magnetic moments remain strongly localized at the line defect, a one-dimensional spin channel gets created in silicene. Interestingly, these spin channels are quite stable because, unlike the edge of nanoribbons, structural reconstruction or contamination cannot destroy the ordering of magnetic moments here. Zigzag silicene nanoribbons with a 5-5-8 line defect also exhibit various interesting electronic and magnetic properties depending upon their width as well as the nature of the magnetic coupling between edge and defect spin states. Upon incorporation of other ELDs, such as 4-4-4 and 4-8 defects, 2D sheets and nanoribbons of silicene show a nonmagnetic metallic or semiconducting ground state. Highlighting the controlled formation of ELDs and consequent emergence of technologically important properties in silicene, we propose new routes to realize silicene-based nanoelectronic and spintronic devices.

  3. Electrical fingerprint of pipeline defects

    Energy Technology Data Exchange (ETDEWEB)

    Mica, Isabella [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)]. E-mail: isabella.mica@st.com; Polignano, Maria Luisa [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy); Marco, Cinzia De [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)

    2004-12-15

    Pipeline defects are dislocations that connect the source region of the transistor with the drain region. They were widely reported to occur in CMOS, BiCMOS devices and recently in SOI technologies. They can reduce device yield either by affecting the devices functionality or by increasing the current consumption under stand-by conditions. In this work the electrical fingerprint of these dislocations is studied, its purpose is to enable us to identify these defects as the ones responsible for device failure. It is shown that the pipeline defects are responsible for a leakage current from source to drain in the transistors. This leakage has a resistive characteristic and it is lightly modulated by the body bias. It is not sensitive to temperature; vice versa the off-current of a good transistor exhibits the well-known exponential dependence on 1/T. The emission spectrum of these defects was studied and compared with the spectrum of a good transistor. The paper aims to show that the spectrum of a defective transistor is quite peculiar; it shows well defined peaks, whereas the spectrum of a good transistor under saturation conditions is characterized by a broad spectral light emission distribution. Finally the deep-level transient spectroscopy (DLTS) is tried on defective diodes.

  4. Intrauterine Infections and Birth Defects

    Institute of Scientific and Technical Information of China (English)

    XIAO-YING ZHENG; XIN-MING SONG; LI-HUA PANG; YING JI; HONG-MEI SUN; LEI ZHANG; JU-FEN LIU; YAN-LING GUO; YAN ZHANG; TING ZHANG; YI-FEI WANG; CHEN XU; GONG CHEN; RUOLEI XIN; JIA-PENG CHEN; XU-MEI HU; QING YANG

    2004-01-01

    Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.

  5. Topological defects from the multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jun [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Blanco-Pillado, Jose J. [Department of Theoretical Physics, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, 48013, Bilbao (Spain); Garriga, Jaume [Departament de Fisica Fonamental i Institut de Ciencies del Cosmos, Universitat de Barcelona, Marti i Franques, 1, 08028, Barcelona (Spain); Vilenkin, Alexander [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States)

    2015-05-28

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble.

  6. Topological defects from the multiverse

    Science.gov (United States)

    Zhang, Jun; Blanco-Pillado, Jose J.; Garriga, Jaume; Vilenkin, Alexander

    2015-05-01

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble.

  7. Topological Defects from the Multiverse

    CERN Document Server

    Zhang, Jun; Garriga, Jaume; Vilenkin, Alexander

    2015-01-01

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly e...

  8. Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

    Science.gov (United States)

    Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Gilchrist, James J; Graham, Stephen M; Pensulo, Paul; Mwimaniwa, Grace; Banda, Meraby; Taylor, Terrie E; Molyneux, Elizabeth E; Drayson, Mark T; Ward, Steven A; Molyneux, Malcolm E; MacLennan, Calman A

    2015-11-18

    Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69(+) NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4(+) lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.

  9. T- and B-lymphocyte chimerism in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Niblack, G.D.; Kateley, J.R.; Gengozian, N.

    1977-01-01

    Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vascular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields >95% T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yields >95% B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.

  10. Defects formation and wave emitting from defects in excitable media

    Science.gov (United States)

    Ma, Jun; Xu, Ying; Tang, Jun; Wang, Chunni

    2016-05-01

    Abnormal electrical activities in neuronal system could be associated with some neuronal diseases. Indeed, external forcing can cause breakdown even collapse in nervous system under appropriate condition. The excitable media sometimes could be described by neuronal network with different topologies. The collective behaviors of neurons can show complex spatiotemporal dynamical properties and spatial distribution for electrical activities due to self-organization even from the regulating from central nervous system. Defects in the nervous system can emit continuous waves or pulses, and pacemaker-like source is generated to perturb the normal signal propagation in nervous system. How these defects are developed? In this paper, a network of neurons is designed in two-dimensional square array with nearest-neighbor connection type; the formation mechanism of defects is investigated by detecting the wave propagation induced by external forcing. It is found that defects could be induced under external periodical forcing under the boundary, and then the wave emitted from the defects can keep balance with the waves excited from external forcing.

  11. Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

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

    1986-01-01

    in concentrations 10 times higher than serum values obtained in clinical practice inhibited lymphocyte proliferation irreversibly. PYR in concentrations corresponding to clinical practice quickly and irreversibly suppressed the proliferation of PWM-stimulated cells, and more slowly the proliferation of PPD....... 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...

  12. Distribution of Topological Defects on Axisymmetric Surface

    Institute of Scientific and Technical Information of China (English)

    SI Tie-Yan; DUAN Yi-Shi

    2006-01-01

    We propose a general method of determining the distribution of topological defects on axisymmetric surface,and study the distribution of topological defects on biconcave-discoid surface, which is the geometric configuration of red blood cell. There are three most possible cases of the distribution of the topological defects on the biconcave surface:four defects charged with 1/2, two defects charged with +1, or one defect charged with 2. For the four defect charged with 1/2, they sit at the vertices of a square imbedded in the equator of biconcave surface.

  13. Expansion of NK cells and reduction of NKG2D expression in chronic lymphocytic leukemia. Correlation with progressive disease.

    Directory of Open Access Journals (Sweden)

    Leticia Huergo-Zapico

    Full Text Available The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CD8 T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL.

  14. Prognostic significance of serum immunoglobulin pareprotein in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨舒

    2012-01-01

    Objective To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia(CLL) ,and to explore its clinical associated laboratory features and prognostic implication. Methods Serum protein electrophoresis and immunofixation

  15. Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Guzman, Roberto E; Radi, Zaher A

    2007-02-01

    Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T-cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution.

  16. The nature of the refractive granules in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, N.P. Jr.; Hempelmann, L.H. [Los Alamos Scientific Lab., NM (United States)

    1949-04-19

    The number of refractive bodies in human lymphocytes increases in persons chronically exposed to low level doses of ionizing radiation. The observations of the optical properties, the histochemistry, and the method of formation of these bodies are described.

  17. CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Engel, Ulla; Holck, Susanne

    2016-01-01

    Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively...

  18. SUBTYPES OF B LYMPHOCYTES IN PATIENTS WITH AUTOIMMUNE HEMOCYTOPENIA

    Institute of Scientific and Technical Information of China (English)

    Li-min Xing; Hai-rong Jia; Juan Sun; Chong-li Yang; Zong-hong Shao; Rong Fu; Hong Liu; Jun Shi; Lie Bai; Mei-feng Tu; Hua-quan Wang; Zhen-zhu Cui

    2007-01-01

    Objective To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters.Methods Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed.Results The quantity of CD5+B lymphocytes of AIHA/Evans syndrome (34. 64% ± 19. 81% ) or IRP patients (35.81% ±16.83% ) was significantly higher than that of normal controls (12.00% ±1.97% , P<0. 05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P > 0. 05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r = - 0. 416, P< 0. 05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r = 1. 00, P<0. 05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r = 0. 761, P< 0. 05) and platelet-associated immunoglobulin M (r = 0. 925, P< 0. 05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b = - 0. 289, P< 0. 05), but had no correlation with colony forming unit-erythroid ( r = - 0. 205, P > 0. 05 ) or colony forming unit-granulocyte-macrophage colonies ( r = -0.214, P>0.05).Conclusions The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease

  19. Isochromosome 17q in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Eyad Alhourani

    2015-01-01

    Full Text Available In chronic lymphocytic leukemia (CLL, presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH. Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q; surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12% here studied CLL cases. Six of those cases (~33% had the TP53 deletion accompanied by an i(17q. Interestingly, the cases with i(17q showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q; it may be suggested that the i(17q presents an even more adverse prognostic marker than TP53 deletion alone.

  20. Richter Syndrome in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Vitale, Candida; Ferrajoli, Alessandra

    2016-02-01

    The term Richter syndrome (RS) indicates the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma. RS is a rare complication with an aggressive clinical course, bearing an unfavorable prognosis. In the majority of cases, CLL transforms into RS as diffuse large B cell lymphoma (DLBCL), and a clonal relation between the two processes can be found. However, clonally unrelated RS can occur and transformations to other histologies beside DLBCL have been described. Recent data have shed some light on genetic characteristics that can influence and drive the transformation from CLL to RS. This molecular information has not been translated yet into significant treatment advances, and currently the therapy regimens for RS continue to rely on intensive chemotherapy combinations followed by stem cell transplant in suitable candidates. Based on the rapid pace of discoveries in the field of hematological malignancies and on the recent revolution in the therapeutic landscape for CLL and B cell lymphomas, new therapeutic options for RS might be available in the upcoming years.

  1. Sampling site matters when counting lymphocyte subpopulations.

    Directory of Open Access Journals (Sweden)

    Benson Ogunjimi

    Full Text Available Clinical and scientific work routinely relies on antecubital venipunctures for hematological, immunological or other analyses on blood. This study tested the hypothesis that antecubital veins can be considered to be a good proxy for other sampling sites. Using a hematocytometer and a flow cytometer, we analyzed the cell counts from samples coming from the radial artery, the dorsal hand veins and the antecubital veins from 18 volunteers. Most surprisingly, we identified the greatest difference not to exist between arterial and venous circulation, but between the distal (radial artery & dorsal hand veins and proximal (antecubital veins sampling sites. Naïve T cells had a higher cell count distally compared to proximally and the reverse was true for effector memory T cells. Despite these differences there were high correlations between the different sampling sites, which partially supports our initial hypothesis. Our findings are crucial for the future design and interpretation of immunological research, and for clinical practice. Furthermore, our results suggest a role for interval lymph nodes in the trafficking of lymphocytes.

  2. Leptomeningeal disease in chronic lymphocytic leukemia.

    Science.gov (United States)

    Lange, C P E; Brouwer, R E; Brooimans, R; Vecht, Ch J

    2007-12-01

    Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western hemisphere, with an annual incidence of 3:100000. Commonly patients are asymptomatic but not rarely disease progression occurs in the setting of lymphadenopathy and extensive leukemic burden. Leptomeningeal involvement in patients with CLL is infrequent, with presenting symptoms of headache (23%), acute or chronic changes in mental status (28%), cranial nerve abnormalities (54%) including optic neuropathy (28%), weakness of lower extremities (23%) and cerebellar signs (18%). In this report, we discuss a CLL patient with leptomeningeal involvement, who presented with neurological symptoms as the first clinical sign, and a diagnosis of leptomeningeal was made based on CSF cytology and flow cytometry. Treatment consisted of radiation therapy and intrathecal chemotherapy with arabinoside-cytosine and systemic chemotherapy. On the basis of this patient-report together with 37 other previously reported cases, the clinical characteristics together with treatment options and outcome of leptomeningeal involvement in CLL are reviewed. Our case together with data from the literature indicate that a timely diagnosis and intensive treatment of leptomeningeal disease of CLL may lead to longstanding and complete resolution of neurological symptoms.

  3. Targeting CD20 in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Nahas MR

    2015-03-01

    Full Text Available Myrna R Nahas, Jon E ArnasonBeth Israel Deaconess Medical Center, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL, the most common leukemia in adults, is standardly managed with chemotherapy in combination with the anti-CD20 antibody rituximab. In this review, we discuss the history, use, and evolution of rituximab in the treatment of CLL and explore the next generation CD20 antibodies ofatumumab and obinutuzumab with a focus on recent clinical trials. Increased understanding of the importance of B cell receptor (BCR signaling in CLL has resulted in the development of several drugs with significant clinical activity that are ideally suited for combination with CD20 therapy as is being currently explored. Moving forward, these developments have the potential to result in treatment regimens that do not include traditional chemotherapeutic agents, which is of particular importance in CLL given the late onset of diagnosis and potential frailty of the patients.Keywords: CLL, monoclonal antibody, rituximab, ofatumumab, obinutuzumab

  4. Tumor infiltrating lymphocytes in ovarian cancer.

    Science.gov (United States)

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  5. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  6. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-01-01

    Full Text Available

    Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.

    Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  7. Congenital heart defects and medical imaging.

    Science.gov (United States)

    Gehin, Connie; Ragsdale, Lisa

    2013-01-01

    Radiologic technologists perform imaging studies that are useful in the diagnosis of congenital heart defects in infants and adults. These studies also help to monitor congenital heart defect repairs in adults. This article describes the development and functional anatomy of the heart, along with the epidemiology and anatomy of congenital heart defects. It also discusses the increasing population of adults who have congenital heart defects and the most effective modalities for diagnosing, evaluating, and monitoring congenital heart defects.

  8. Concanavalin A-induced activation of lymphocytic choriomeningitis virus memory lymphocytes into specifically cytotoxic T cells

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup; Andersen, G T

    1977-01-01

    When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A......-stimulated cells is higher than that of non-incubated spleen cells harvested nine days following the primary infection, and the effect is totally inhibited by anti-theta serum plus complement treatment of the effector cells immediately before the cytotoxic test....

  9. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure

    Directory of Open Access Journals (Sweden)

    Erdal Durmus

    2015-01-01

    Full Text Available AbstractBackground:Neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up.Methods:This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization.Results:The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01. There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001. The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average.Conclusion:NLR and PLR were higher in HF patients than in age-sex matched controls. However, NLR and PLR were not sufficient to establish a diagnosis of HF. NLR can be used to predict mortality during the follow-up of HF patients.

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

    Science.gov (United States)

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

    2016-05-01

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

  11. Genotoxicity of the herbicide butachlor in cultured human lymphocytes.

    Science.gov (United States)

    Sinha, S; Panneerselvam, N; Shanmugam, G

    1995-08-01

    Butachlor, a pre-emergence herbicide was investigated for its ability to induce sister chromatid exchanges (SCE) and chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Mitogen-stimulated lymphocytes were treated with three different concentrations (5, 10 and 20 micrograms/ml) of butachlor for 24, 48 and 72 h. Our results indicate a dose-dependent increase in the frequency of chromosomal aberrations at 24, 48 and 72 h of treatment with butachlor. No SCE was promoted by butachlor.

  12. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    OpenAIRE

    Cartwright, R. A.; Bernard, S.M.; Bird, C. C.; Darwin, C. M.; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-01-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, im...

  13. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

    OpenAIRE

    Thomas Walcher; Peter Bernhardt; Dusica Vasic; Helga Bach; Renate Durst; Wolfgang Rottbauer; Daniel Walcher

    2010-01-01

    Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD...

  14. Atomistic stimulation of defective oxides

    CERN Document Server

    Minervini, L

    2000-01-01

    defect processes. The predominant intrinsic disorder reaction and the mechanism by which excess oxygen is accommodated are established. Furthermore, the most favourable migration mechanism and pathway for oxygen ions is predicted. Chapters 7 and 8 investigate pyrochlore oxides. These materials are candidates for solid oxide fuel cell components and as actinide host phases. Such applications require a detailed understanding of the defect processes. The defect energies, displayed as contour maps, are able to account for structure stability and, given an appropriate partial charge potential model, to accurately determine the oxygen positional parameter. In particular, the dependence of the positional parameter on intrinsic disorder is predicted. It is demonstrated, by radiation damage experiments, that these results are able to predict the radiation performance of pyrochlore oxides. Atomistic simulation calculations based on energy minimization techniques and classical pair potentials are used to study several i...

  15. Defect CFTs and holographic multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Fiol, Bartomeu, E-mail: bfiol@ub.edu [Departament de Física Fonamental i Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès 1, 08193 Barcelona (Spain)

    2010-07-01

    We investigate some aspects of a recent proposal for a holographic description of the multiverse. Specifically, we focus on the implications on the suggested duality of the fluctuations of a bubble separating two universes with different cosmological constants. We do so by considering a similar problem in a 2+1 CFT with a codimension one defect, obtained by an M5-brane probe embedding in AdS{sub 4} × S{sup 7}, and studying its spectrum of fluctuations. Our results suggest that the kind of behavior required by the spectrum of bubble fluctuations is not likely to take place in defect CFTs with an AdS dual, although it might be possible if the defect supports a non-unitary theory.

  16. Pathogenesis, prophylaxis and treatment of infections in patients with chronic lymphocytic leukemia 

    Directory of Open Access Journals (Sweden)

    Piotr Stelmach

    2013-06-01

    Full Text Available Chronic lymphocytic leukemia (CLL patients are at high risk for infections. The pathogenesis of infection in patients with this leukemia is complex and multifactorial. Patients with CLL have a number of immune system defects, including disordered B-cell function with decreased production of normal B-cells and abnormal production of immunoglobulins, suppressed Tcell function and neutropenia. Other immune abnormalities present in CLL patients include neutrophil dysfunction, and complement deficiencies. In addition, further perturbations in immune function are related to the antileukemic therapies. Immune disturbance might be common prior to CLL diagnosis and infectious agents could trigger CLL development. Current chemotherapy-based regimens are not curative and often worsen this immune suppression. The introduction of new effective therapeutic agents such as the purine analogues and monoclonal antibodies has influenced the spectrum of infections diagnosed in CLL patients. Some conditions increase the risk for the development of infections including advanced age, decreased levels of immunoglobulins, advanced Binet stage, neutropenia and treatment with more than one line of chemotherapy. Until now it is debatable whether and when antibacterial prophylaxis could be useful in CLL patients. The prevention of infection includes antimicrobial prophylaxis, as well as immunoglobulin replacement and vaccination. Antibacterial prophylaxis should be given to CLL patients with previous severe and/or relapsing bacterial infections. This article reviews the immune defects in CLL and discusses strategies aimed at prophylaxis and treatment of infections in patients with CLL. 

  17. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

    Directory of Open Access Journals (Sweden)

    ALEX J.L. TORRES

    2015-06-01

    Full Text Available The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+ and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34 and females (35 were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186 cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62 and 24% (9-28, respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03 in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

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

    Directory of Open Access Journals (Sweden)

    Zhao Sun

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

  19. The lymphocyte transformation test in allergic contact dermatitis: New opportunities.

    Science.gov (United States)

    Popple, Amy; Williams, Jason; Maxwell, Gavin; Gellatly, Nichola; Dearman, Rebecca J; Kimber, Ian

    2016-01-01

    Allergic contact dermatitis (ACD) is driven by the activation and proliferation of allergen-specific memory T-lymphocytes and is currently diagnosed by patch testing with a selected panel of chemical allergens. The lymphocyte transformation test (LTT) can be used to monitor ex vivo T-lymphocyte responses to antigens, including contact allergens. The LTT is not viewed as being an alternative to patch testing, but it does seek to reflect experimentally skin sensitization to specific chemicals. The LTT is based on stimulation in vitro of antigen-driven T-lymphocyte proliferation. That is, exposure in culture of primed memory T-lymphocytes to the relevant antigen delivered in an appropriate configuration will provoke a secondary response that reflects the acquisition of skin sensitization. The technical aspects of this test and the utility of the approach for investigation of immune responses to contact allergens in humans are reviewed here, with particular emphasis on further development and refinement of the protocol. An important potential application is that it may provide a basis for characterizing those aspects of T-lymphocyte responses to contact allergens that have the greatest influence on skin sensitizing potency and this will be considered in some detail.

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

    Science.gov (United States)

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

    2003-01-01

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

  1. Alarming Rise In Birth Defects

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A rapid rise in birth defects has prompted China to look for causes and solutionsEvery 60 seconds two children are born in China with a handicap.It’s an alarming fact,but one that young adults across the country who hope to have children face every day. At a conference on the prevention of birth defects in Chengdu of Sichuan Province in September,Vice Minister of the National Population and Family Planning Commission Jiang Fan revealed this inconvenient truth, supported by shocking statistics.

  2. Atrial – Ventricular Septal Defect

    Directory of Open Access Journals (Sweden)

    T Panagiotopoulos

    2009-05-01

    Full Text Available Atrial and ventricular septal defect constitute the most common congenital heart disease.Aim: Τhe aim of the present retrospective study was to record data and factors that affect atrial and ventricular septal defect.Method and material: The sample study included patients of both sexes who were hospitalized with diagnosis atrial and ventricular septal defect in a Cardiac Surgery hospital of Athens. A specially constructed printed form was used for data collection, where were recorded the demographic and personal variables, the pathological, surgical, cardiology and obstetric history, the habits of adults, as well as the personal characteristics of mothers. Analysis of data was performed by descriptive statistical analysis.Results: The sample study consisted of 101 individuals with diagnosis atrial or ventricular Septal Defect, of which 40% were boys and 60% girls. The 70% of the sample study suffered from atrial Septal Defect and the 30% suffered from ventricular Septal Defect. Regarding age, 12% of the sample study was 0-1 years old, 35% was >1 years old, 8% was >12-18 years old and 45% over than 18 years old. Regarding educational status of the adult participants, 9% was of 0-6 years education, 22%>6 -12 years, 13%>12 years. 14% of the adult paticipants smoked, 4% consumed alcohol and 5% smoked in conjunction with alcohol. In terms of the obstetric history of the sample studied, 32% of the cases had normal birth, 4% had a twin birth and 1% had a triplet one. According to the variables related to mothers, the mean age of the mother was 30 years and 3 months, 10% were smokers at pregnancy and 3% used chemical substance and mainly hair color. Also, the results of the present study showed that individuals of 12-18 and >18 years old did not suffer from ventricular Septal Defect, whereas the infants 0-1 years old did not suffer from Atrial Septal Defect. The mean value of age at the admission in intensive care unit was 7 months (12% for the infants

  3. Facts about Upper and Lower Limb Reduction Defects

    Science.gov (United States)

    ... Heart Defects Atrial Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great ... Defects Fetal Alcohol Syndrome Disorders Gastroschisis Heart Defects Coarctation of the Aorta Hypoplastic left heart syndrome Tetralogy ...

  4. MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Marker, O

    1989-01-01

    The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion, indicat......The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion...

  5. Chronic Brucellosis Patients Retain Low Frequency of CD4+ T-Lymphocytes Expressing CD25 and CD28 after Escherichia coli LPS Stimulation of PHA-Cultured PBMCs

    Directory of Open Access Journals (Sweden)

    Panagiotis Skendros

    2008-01-01

    Full Text Available Chronic brucellosis patients display a defective Th1 response to PHA. We have previously shown that heat-killed B. abortus (HKBA can downregulate the PHA-induced increase of CD4+/CD25+ and CD14+/CD80+ cells of brucellosis patients. In the present study, we investigate the effect of E. coli LPS, as a potent stimulant of monocytes and autologous T-lymphocytes, on the PHA-cultured PBMCs of the same groups of patients. Thirteen acute brucellosis (AB patients, 22 chronic brucellosis (CB patients, 11 “cured” subjects, and 15 healthy volunteers were studied. The percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes as well as CD14+/CD80+ monocytes were analyzed by flow cytometry after PBMCs culture with PHA plus E. coli LPS. A significant decrease in the percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes was observed in CB compared to AB. In HKBA cultures, compared to E. coli LPS-cultures, there was a significant reduction of CD4+/CD25+ T-lymphocytes in all groups and CD14+/CD80+ in patients groups. We suggest that Brucella can modulate host immune response, leading to T-cell anergy and chronic infection.

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Nasr, Samih H; Shanafelt, Tait D; Hanson, Curtis A; Fidler, Mary E; Cornell, Lynn D; Sethi, Sanjeev; Chaffee, Kari G; Morris, Joseph; Leung, Nelson

    2015-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon pathologic lesion encountered in 0.5% to 5.9% of renal biopsies. Drugs, sarcoidosis, and infections are responsible for most cases of GIN. Malignancy is not an established cause of GIN. Here, we report a series of 5 patients with GIN secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients were mostly elderly white males with an established history of CLL/SLL who presented with severe renal impairment (median peak serum creatinine, 7.3 mg/dL), leukocyturia, and mild proteinuria. One had nephromegaly. In 2 patients, the development and relapse of renal insufficiency closely paralleled the level of lymphocytosis. Kidney biopsy in all patients showed GIN concomitant with CLL/SLL leukemic interstitial infiltration. Granulomas were nonnecrotizing and epithelioid and were associated with giant cells. One biopsy showed granulomatous arteritis. One patient had a granulomatous reaction in lymph nodes and skin. Steroids with/without CLL/SLL-directed chemotherapy led to partial improvement of kidney function in all patients except 1 who had advanced cortical scarring on biopsy. In conclusion, we report an association between CLL/SLL and GIN. Patients typically present with severe renal failure due to both GIN and leukemic interstitial infiltration, which tends to respond to steroids with/without CLL/SLL-directed chemotherapy. The pathogenesis of GIN in this clinical setting is unknown but may represent a local hypersensitivity reaction to the CLL/SLL tumor cells.

  8. Types of Congenital Heart Defects

    Science.gov (United States)

    ... Doctors use open-heart surgery to repair VSDs. Patent Ductus Arteriosus Patent ductus arteriosus (PDA) is a fairly common heart defect that ... ductus arteriosus closes. In some babies, however, the ductus arteriosus remains open (patent). The opening allows oxygen-rich blood from the ...

  9. Genetic defects of iron transport.

    Science.gov (United States)

    Bannerman, R M

    1976-09-01

    Five genetic traits in man and laboratory animals have major effects on iron transport. The heterogeneous condition, hemochromatosis, in some families appears to segregate as a Mendelian trait, and is associated with defective control of intestinal iron absorption. In the very rare human autosomal recessive trait, atransferrinemia, there is an almost total lack of transferrin and gross maldistribution of iron through the body. In mice, sex-linked anemia (an X-linked recessive trait) causes iron deficiency through defective iron absorption, at the "exit" step; a similar defect probably exists in placental iron transfer. In microcytic anemia of mice, an autosomal recessive trait, iron absorption is also impaired because of a defect of iron entry into cells, which is probably generalized. Belgrade rat anemia, less understood at present, also may involve a major disorder of iron metabolism. Study of these mutations has provided new knowledge of iron metabolism and its genetic control Their phenotypic interaction with nutritional factors, especially the form and quantity of iron in the diet, may provide new insights for the study of nutrition.

  10. Ocular defects in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Katoch Sabita

    2007-01-01

    Full Text Available There is a high prevalence of ocular defects in children with developmental disabilities. This study evaluated visual disability in a group of 200 cerebral palsy (CP patients and found that 68% of the children had significant visual morbidity. These findings emphasize the need for an early ocular examination in patients with CP.

  11. Nuclear Pasta: Topology and Defects

    Science.gov (United States)

    da Silva Schneider, Andre; Horowitz, Charles; Berry, Don; Caplan, Matt; Briggs, Christian

    2015-04-01

    A layer of complex non-uniform phases of matter known as nuclear pasta is expected to exist at the base of the crust of neutron stars. Using large scale molecular dynamics we study the topology of some pasta shapes, the formation of defects and how these may affect properties of neutron star crusts.

  12. Brane Inflation and Defect Formation

    CERN Document Server

    Davis, A C; Van de Bruck, C

    2008-01-01

    Brane inflation and the production of topological defects at the end of the inflationary phase are discussed. After a description of the inflationary setup we discuss the properties of the cosmic strings produced at the end of inflation. Specific examples of brane inflation are described: $D-\\bar D$ inflation, $D3/D7$ inflation and modular inflation

  13. Hamiltonian monodromy as lattice defect

    OpenAIRE

    Zhilinskii, B.

    2003-01-01

    The analogy between monodromy in dynamical (Hamiltonian) systems and defects in crystal lattices is used in order to formulate some general conjectures about possible types of qualitative features of quantum systems which can be interpreted as a manifestation of classical monodromy in quantum finite particle (molecular) problems.

  14. Prognostic impact of lymphocytes in soft tissue sarcomas.

    Directory of Open Access Journals (Sweden)

    Sveinung W Sorbye

    Full Text Available PURPOSE: The purpose of this study was to clarify the prognostic significance of lymphocyte infiltration in soft tissue sarcomas (STS. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of tumor infiltrating lymphocytes is controversial as the immune system has conflicting roles during cancer development. EXPERIMENTAL DESIGN: Tissue microarrays from 249 patients with STS were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+, CD20+ and CD45+ lymphocytes in tumors. RESULTS: In univariate analyses, increased numbers of CD4+ (P = 0.008 and CD20+ (P = 0.006 lymphocytes in tumor correlated significantly with an improved disease-specific survival (DSS in patients with wide resection margins (n = 108. In patients with non-wide resection margins (n = 141 increased numbers of CD3+ (P = 0.028 lymphocytes in tumor correlated significantly with shorter DSS. In multivariate analyses, a high number of CD20+ lymphocytes (HR = 5.5, CI 95%  = 1.6-18.6, P = 0.006 in the tumor was an independent positive prognostic factor for DSS in patients with wide resections margins. CONCLUSIONS: High density of CD20+ lymphocytes in STS with wide resection margins is an independent positive prognostic indicator for these patients. Further research is needed to define if CD20+ cells can modify tumors in a way that reduces disease progression and metastatic potential.

  15. Casting defects analysis by the Pareto method

    Directory of Open Access Journals (Sweden)

    B. Borowiecki

    2011-07-01

    Full Text Available On the basis of receive results formed of diagram Pareto Lorenz. On the basis of receive graph it affirmed, that for 70% general number casting defects answered 3 defects (9 contribution – 100% defects. For 70% general number defects of influence it has three type of causes: sand holes, porosity and slaginclusions. Thedefects show that it is necessary to take up construction gatingsystem. The remaining 8 causes have been concerned only 25%, with general number of casting defects. Analysis of receive results permit to determine of direction of correct actions in order to eliminate or to limit the most defects.

  16. Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

    Science.gov (United States)

    Dardick, I; Caldwell, D R; Moher, D; Jabi, M

    1988-08-01

    Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even

  17. Apoptosis of matured T lymphocytes induced by mouse sertoli cells in cocultures in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Yang; LIN Zi-hao; ZHU Xiao-hai; LIU Shan-rong

    2001-01-01

    Objective: To study whether mouse sertoli cells can induce the apoptosis of matured T lymphocytes in cocultures in vitro. Methods: With TUNEL, DNA electrophoresis, eleetro-mierography and flow cytometry, we examined the apoptosis and its rates of mouse matured T lymphocytes in control group (T lymphocytes only), group A (T lymphocytes + culture medium of sertoli cells), group B (T lymphocytes + sertoli cells). Results: Under electro-micrography, chromatin condensation, karyopyknosis, karyorhexis and apoptotic body were observed in some T lymphocytes in 3 groups; some nucleuses were stained dark blue with TUNEL; a typical DNA ladder was found with DNA electrophoresis. The apoptotic rates of T lymphocytes in group A and B were significantly higher than that in control group (P<0.01). The apoptotic rate of T lymphocytes in group B was significantly higher than that in group A (P<0.01). Conclusion: In coculture condition in vitro,mouse sertoli cells can induce the apoptosis of matured T lymphocytes.

  18. Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Prusek, W. (Szpital Wojewodzki, Wroclaw (Poland)); Astaldi, G. (The Blood Research Foundation Centre, Tortona (Italy))

    1979-01-01

    The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than the viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so-called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity.

  19. Point defects in crystals (including grouped defects). Report No. 4548

    Energy Technology Data Exchange (ETDEWEB)

    Seidman, D.N.

    1981-08-01

    The fundamental properties of point defects, vacancies and self-interstitial atoms, in pure fcc and bcc metals is reviewed. Point defects created by both thermally-activated and irradiation processes are considered. The roles played by vacancies and self-interstitial atoms in thermal equilibrium are discussed and the best values of the enthalpy of formation of these point defects, in a number of metals, are given. Methods for obtaining fundamental properties of vacancies, such as activation volumes, mobilities, and binding enthalpies are discussed. Selected best values of mobilities and binding enthalpies of vacancies, as deduced from recovery experiments on a number of different quenched metals are listed. The problem of the production of single self-interstitial atoms and their configuration(s) is discussed. The clustering of single self-interstitials into small clusters is also considered. The physical origin of the extremely high low-temperature mobility of self-interstitials in the so-called Stage I recovery regime is also discussed.

  20. Cytotoxic T lymphocytes specific for the simian immunodeficiency virus.

    Science.gov (United States)

    Letvin, N L; Schmitz, J E; Jordan, H L; Seth, A; Hirsch, V M; Reimann, K A; Kuroda, M J

    1999-08-01

    A non-human primate model for acquired immunodeficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, was used to explore the role of the AIDS virus-specific cytotoxic T-lymphocyte (CTL) response in disease pathogenesis. This CTL response was measured using the major histocompatibility complex (MHC) class I/peptide tetramer technology. Large numbers of tetramer-binding CD8+ T lymphocytes were demonstrable not only in the peripheral blood, but in lymph nodes and even in semen of chronically SIV-infected monkeys. The central role of these effector T lymphocytes in containing SIV spread during primary infection was demonstrated by showing that early SIV clearance during primary infection correlated with the emergence of the tetramer binding CD8+ T lymphocytes and that in vivo depletion of CD8+ lymphocytes eliminated the ability of the infected monkeys to contain SIV replication. These observations suggest that an effective AIDS vaccine should elicit a potent virus-specific CTL response. In fact, a live, recombinant SIV vaccine constructed using the attenuated pox virus vector modified vaccinia Ankara (MVA) elicited a high-frequency CTL response, comparable in magnitude to that elicited by SIV infection itself. This suggests that vaccine modalities such as MVA may prove useful in creating an effective human immunodeficiency virus (HIV) vaccine. These studies also indicate the power of both the SIV/macaque model and MHC class I/peptide tetramers for assessing AIDS vaccine strategies.

  1. Antibody production in early life supported by maternal lymphocyte factors.

    Science.gov (United States)

    Shimamura, Michio; Huang, Yi-Ying; Goji, Hiroshi

    2003-01-20

    To examine the influence of maternal lymphocyte factors on the immune responses in offspring in early life, antibody production in neonates born to either normal or lymphocyte-deficient mothers was analyzed. Recombination activating gene (Rag)-2(+/-) mouse neonates born to Rag-2(+/+), Rag-2(+/-)or Rag-2(-/-)mothers were injected with goat anti-mouse IgD antiserum, and IgE and IgG(1) production was evaluated. The levels of IgE and IgG(1) were higher in the pups born to Rag-2(+/+)and Rag-2(+/-) dams than to lymphocyte-deficient Rag-2(-/-) dams. The enhanced antibody production in the former compared with the latter neonates was also found following immunization with ovalbumin or TNP-Ficoll. Thus, the presence of maternal lymphocyte factors was suggested in neonates that augmented antigen-specific antibody production in both T cell-dependent and -independent pathways. A reduction in antibody production was observed in normal neonates when they were foster-nursed by Rag-2(-/-) mothers. Thus, the maternal lymphocyte factors enhancing the immune responses in newborns were shown to be present in breast-milk.

  2. 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

  3. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

    Directory of Open Access Journals (Sweden)

    Thomas Walcher

    2010-01-01

    Full Text Available Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7. Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7. The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC. Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.

  4. Cellular Defect May Be Linked to Parkinson's

    Science.gov (United States)

    ... 160862.html Cellular Defect May Be Linked to Parkinson's: Study Abnormality might apply to all forms of ... that may be common to all forms of Parkinson's disease. The defect plays a major role in ...

  5. Opioid Use and Neural Tube Defects

    Science.gov (United States)

    ... CDC.gov . Articles Key Findings: Opioid Use and Neural Tube Defects Recommend on Facebook Tweet Share Compartir The ... relationship to having a pregnancy affected by a neural tube defect (NTD). Researchers from Boston University and CDC ...

  6. Expert Network for Die Casing Defect Analysis

    Institute of Scientific and Technical Information of China (English)

    Jiadi WANG; Yongfeng JIANG; Chen LU; Wenjiang DING

    2003-01-01

    Due to the competition and high cost associated with die casting defects, it is urgent to adopt a rapid and effective method for defect analysis. In this research, a novel expert network approach was proposed to avoid some disadvantages of rulebased expert system. The main objective of the system is to assist die casting engineer in identifying defect, determining the probable causes of defect and proposing remedies to eliminate the defect. 14 common die casting defects could be identified quickly by expert system on the basis of their characteristics. BP neural network in combination with expert system was applied to map the complex relationship between causes and defects, and further explained the cause determination process.Cause determination gives due consideration to practical process conditions. Finally, corrective measures were recommended to eliminate the defect and implemented in the sequence of difficulty.

  7. NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

    Science.gov (United States)

    Cukic, Vesna

    2016-01-01

    Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surgery). 57 of patients with NSCLC treated in the first three months of 2016. year were chosen at random regardless of sex and age. We examined full blood count cells (FBC), calculated NLR and PLR in every patient and compared obtained values in patients with and patients without metastases. Results: In 57 patients with NSCLC there were 15 males with metastases, 28 without metastases, and 8 females with metastases, 6 without metastases. Since there was no regularity in the distribution of obtained values of NLR and PLR we made the Mann-Whitney U test. Mean values are presented with a median and interquartile percentiles. There was no significant difference in NLR between patients without and with metastases (p = 0.614; p = NS) as well as in PLR (p=0,068; p=NS). Conclusion: There must be a link between the immune status of the organism and lung cancer development. Immune cells have become of interest in recent years and much work has been done to study their role in the genesis of cancer but it did not give satisfactory results. Further clinical studies on large number of patients and further laboratory examination of the role of immune cells in cancer development and suppression are required. PMID:27999489

  8. Automatic classification of blank substrate defects

    Science.gov (United States)

    Boettiger, Tom; Buck, Peter; Paninjath, Sankaranarayanan; Pereira, Mark; Ronald, Rob; Rost, Dan; Samir, Bhamidipati

    2014-10-01

    Mask preparation stages are crucial in mask manufacturing, since this mask is to later act as a template for considerable number of dies on wafer. Defects on the initial blank substrate, and subsequent cleaned and coated substrates, can have a profound impact on the usability of the finished mask. This emphasizes the need for early and accurate identification of blank substrate defects and the risk they pose to the patterned reticle. While Automatic Defect Classification (ADC) is a well-developed technology for inspection and analysis of defects on patterned wafers and masks in the semiconductors industry, ADC for mask blanks is still in the early stages of adoption and development. Calibre ADC is a powerful analysis tool for fast, accurate, consistent and automatic classification of defects on mask blanks. Accurate, automated classification of mask blanks leads to better usability of blanks by enabling defect avoidance technologies during mask writing. Detailed information on blank defects can help to select appropriate job-decks to be written on the mask by defect avoidance tools [1][4][5]. Smart algorithms separate critical defects from the potentially large number of non-critical defects or false defects detected at various stages during mask blank preparation. Mechanisms used by Calibre ADC to identify and characterize defects include defect location and size, signal polarity (dark, bright) in both transmitted and reflected review images, distinguishing defect signals from background noise in defect images. The Calibre ADC engine then uses a decision tree to translate this information into a defect classification code. Using this automated process improves classification accuracy, repeatability and speed, while avoiding the subjectivity of human judgment compared to the alternative of manual defect classification by trained personnel [2]. This paper focuses on the results from the evaluation of Automatic Defect Classification (ADC) product at MP Mask

  9. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  10. Cooperation and Defection in Ghetto

    Science.gov (United States)

    Kułakowski, Krzysztof

    We consider ghetto as a community of people ruled against their will by an external power. Members of the community feel that their laws are broken. However, attempts to leave ghetto makes their situation worse. We discuss the relation of the ghetto inhabitants to the ruling power in context of their needs, organized according to the Maslow hierarchy. Decisions how to satisfy successive needs are undertaken in cooperation with or defection the ruling power. This issue allows to construct the tree of decisions and to adopt the pruning technique from the game theory. Dynamics of decisions can be described within the formalism of fundamental equations. The result is that the strategy of defection is stabilized by the estimated payoff.

  11. Correlation functions on conical defects

    CERN Document Server

    Smolkin, Michael

    2015-01-01

    We explore the new technique developed recently in \\cite{Rosenhaus:2014woa} and suggest a correspondence between the $N$-point correlation functions on spacetime with conical defects and the $(N+1)$-point correlation functions in regular Minkowski spacetime. This correspondence suggests a new systematic way to evaluate the correlation functions on spacetimes with conical defects. We check the correspondence for the expectation value of a scalar operator and of the energy momentum tensor in a conformal field theory and obtain the exact agreement with the earlier derivations for cosmic string spacetime. We then use this correspondence and do the computations for a generic scalar operator and a conserved vector current. For generic unitary field theory we compute the expectation value of the energy momentum tensor using the known spectral representation of the $2$-point correlators of stress-energy tensor in Minkowski spacetime.

  12. Cooperation and defection in ghetto

    CERN Document Server

    Kulakowski, K

    2006-01-01

    We consider ghetto as a community of people ruled against their will by an external power. Members of the community feel that their laws are broken. However, attempts to leave ghetto makes their situation worse. We discuss the relation of the ghetto inhabitants to the ruling power in context of their needs, organized according to the Maslow hierarchy. Decisions how to satisfy successive needs are undertaken in cooperation with or defection the ruling power. This issue allows to construct the tree of decisions and to adopt the pruning technique from the game theory. Dynamics of decisions can be described within the formalism of fundamental equations. The result is that the strategy of defection is stabilized by the estimated payoff.

  13. Serglycin determines secretory granule repertoire and regulates natural killer cell and cytotoxic T lymphocyte cytotoxicity.

    Science.gov (United States)

    Sutton, Vivien R; Brennan, Amelia J; Ellis, Sarah; Danne, Jill; Thia, Kevin; Jenkins, Misty R; Voskoboinik, Ilia; Pejler, Gunnar; Johnstone, Ricky W; Andrews, Daniel M; Trapani, Joseph A

    2016-03-01

    The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated. Reduced intracellular granzyme B levels were noted, particularly in CD27(+) CD11b(+) mature NK cells, whereas serglycin(-/-) TCR-transgenic (OTI) CD8 T cells also had reduced perforin stores. Culture supernatants from serglycin(-/-) OTI T cells and interleukin-2-activated NK contained increased granzyme B, linking reduced storage with heightened export. By contrast, granzyme A was not significantly reduced in cells lacking serglycin, indicating differentially regulated trafficking and/or storage for the two granzymes. A quantitative analysis of different granule classes by transmission electronmicroscopy showed a selective loss of dense-core granules in serglycin(-/-) CD8(+) CTLs, although other granule types were maintained quantitatively. The findings of the present study show that serglycin plays a critical role in the maturation of dense-core cytotoxic granules in cytotoxic lymphocytes and the trafficking and storage of perforin and granzyme B, whereas granzyme A is unaffected. The skewed retention of cytotoxic effector molecules markedly reduces CTL/NK cell cytotoxicity, although this is partly compensated for as a result of activating the cells by physiological means.

  14. Confining crack propagation in defective graphene.

    Science.gov (United States)

    López-Polín, Guillermo; Gómez-Herrero, Julio; Gómez-Navarro, Cristina

    2015-03-11

    Crack propagation in graphene is essential to understand mechanical failure in 2D materials. We report a systematic study of crack propagation in graphene as a function of defect content. Nanoindentations and subsequent images of graphene membranes with controlled induced defects show that while tears in pristine graphene span microns length, crack propagation is strongly reduced in the presence of defects. Accordingly, graphene oxide exhibits minor crack propagation. Our work suggests controlled defect creation as an approach to avoid catastrophic failure in graphene.

  15. Electricity Surcharges: Defects and Suggestions

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Since 1980s, the government has decided to levy certain surcharges attached to electricity tariff collected by power grid corporations as government revenue for specific social public welfare purposes. These surcharges presently include the Three Gorges construction fund, urban construction surcharge, rural power grid debt service fund, as well as the newly-added post supporting fund for water reservoirs immigrants and renewable energy surcharge, etc. Yet the legal defects on surcharge policy have brought about operational risks on power grid enterprises.

  16. Packing defects into ordered structures

    DEFF Research Database (Denmark)

    Bechstein, R.; Kristoffersen, Henrik Høgh; Vilhelmsen, L.B.

    2012-01-01

    We have studied vicinal TiO2(110) surfaces by high-resolution scanning tunneling microscopy and density functional theory calculations. On TiO2 surfaces characterized by a high density of ⟨11̅ 1⟩ steps, scanning tunneling microscopy reveals a high density of oxygen-deficient strandlike adstructur...... because building material is available at step sites. The strands on TiO2(110) represent point defects that are densely packed into ordered adstructures....

  17. Diabetic angiopathy and angiogenic defects

    Directory of Open Access Journals (Sweden)

    Xu Ling

    2012-08-01

    Full Text Available Abstract Diabetes is one of the most serious health problems in the world. A major complication of diabetes is blood vessel disease, termed angiopathy, which is characterized by abnormal angiogenesis. In this review, we focus on angiogenesis abnormalities in diabetic complications and discuss its benefits and drawbacks as a therapeutic target for diabetic vascular complications. Additionally, we discuss glucose metabolism defects that are associated with abnormal angiogenesis in atypical diabetic complications such as cancer.

  18. Algorithms for defects in nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Chan, T.-L.; Tiago, Murilo L. [Center for Computational Materials, Institute for Computational Engineering and Sciences, University of Texas, Austin, Texas 78712 (United States); Chelikowsky, James R. [Center for Computational Materials, Institute for Computational Engineering and Sciences, University of Texas, Austin, Texas 78712 (United States); Departments of Physics and Chemical Engineering, University of Texas, Austin, Texas 78712 (United States)], E-mail: jrc@ices.utexas.edu

    2007-12-15

    We illustrate recent progress in developing algorithms for solving the Kohn-Sham problem. Key ingredients of our algorithm include pseudopotentials implemented on a real space grid and the use of damped-Chebyshev polynomial filtered subspace iteration. This procedure allows one to predict electronic properties for many materials across the nano-regime, i.e., from atoms to nanocrystals of sufficient size to replicate bulk properties. We will illustrate this method for large silicon quantum dots doped with phosphorus defect.

  19. Photonic crystals with topological defects

    Science.gov (United States)

    Liew, Seng Fatt; Knitter, Sebastian; Xiong, Wen; Cao, Hui

    2015-02-01

    We introduce topological defects to a square lattice of elliptical cylinders. Despite the broken translational symmetry, the long-range positional order of the cylinders leads to a residual photonic band gap in the local density of optical states. However, the band-edge modes are strongly modified by the spatial variation of the ellipse orientation. The Γ -X band-edge mode splits into four regions of high intensity and the output flux becomes asymmetric due to the formation of crystalline domains with different orientation. The Γ -M band-edge mode has the energy flux circulating around the topological defect center, creating an optical vortex. By removing the elliptical cylinders at the center, we create localized defect states, which are dominated by either clockwise or counterclockwise circulating waves. The flow direction can be switched by changing the ellipse orientation. The deterministic aperiodic variation of the unit cell orientation adds another dimension to the control of light in photonic crystals, enabling the creation of a diversified field pattern and energy flow landscape.

  20. Signs and Symptoms of Congenital Heart Defects

    Science.gov (United States)

    ... Twitter. What Are the Signs and Symptoms of Congenital Heart Defects? Many congenital heart defects cause few or no signs and symptoms. A ... lips, and fingernails) Fatigue (tiredness) Poor blood circulation Congenital heart defects don't cause chest pain or other painful ...

  1. Care and Treatment for Congenital Heart Defects

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Care and Treatment for Congenital Heart Defects Updated:Oct 26,2015 Not all people with ... supports you in your pursuit of heart health. Congenital Heart Defects • Home • About Congenital Heart Defects • The Impact of ...

  2. Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

    Science.gov (United States)

    Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.

    2006-10-01

    Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

  3. Cytotoxicity and genotoxicity of gliotoxin on human lymphocytes in vitro

    Directory of Open Access Journals (Sweden)

    Mohammed Adel Nouri

    2015-07-01

    Full Text Available The cytotoxic effects on human lymphocytes of two gliotoxin samples (one pure sample produced in the laboratory for this study, and one sample purchased from a standard source were assessed at four different concentrations (25, 50, 100 and 200 ng/ml using the methylthiazol tetrazolium (MTT bioassay. The results showed that growth was inhibited by 21, 39.10, 61.99 and 87.45% for each of the four concentrations of the pure sample, respectively, and by 17.89, 34.92, 58.34 and 85.22% respectively, in the case of the standard purchased sample. Deoxyribonucleic acid (DNA was extracted from the lymphocytes and analysed by electrophoresis on a 1% agarose gel. Gliotoxin appeared to have the ability to degrade or damage the DNA. The present study showed that both the growth inhibition and DNA damage experienced by the human lymphocytes increased linearly with increasing concentrations of toxin.

  4. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  5. Key role of mitochondria in apoptosis of lymphocytes.

    Science.gov (United States)

    Boichuk, S V; Minnebaev, M M; Mustafin, I G

    2001-12-01

    Changes in the mitochondrial potential, expression of phosphatidylserine, parameters of direct and lateral light scattering, and DNA fragmentation during spontaneous and induced apoptosis in peripheral blood lymphocytes were studied by flow cytofluorometry. Dexamethasone and Ca2+ ionophore A23187 served as inductors of apoptosis. A decrease in the mitochondrial potential is an early sign of spontaneous and induced apoptosis. Phosphatidylserine expression on the outer plasma membrane occurred later and inversely depended on the mitochondrial potential. Our results indicate that the involvement of mitochondria in spontaneous and induced apoptosis accompanied by a decrease in the mitochondrial potential is an early and key event of programmed lymphocyte death. The decrease in the mitochondrial potential of lymphocytes induced degradation of their nuclei (DNA fragmentation) and promoted elimination of apoptotic cells (phosphatidylserine expression).

  6. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Science.gov (United States)

    Vuento, R

    1983-04-01

    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

  7. Human lymphocyte sub-populations and K cells.

    Science.gov (United States)

    Sandilands, G; Gray, K; Cooney, A; Froebel, K; Anderson, J R

    1976-01-01

    Peripheral blood lymphocytes from 19 normal subjects were examined for surface Ig (SIg) and capacity to form rosettes with normal and neuraminidase-treated sheep erythrocytes and with chicken erythrocytes sensitised with IgG antibody. Information on the relationship between the presence of SIg and capacity to form rosettes was obtained by combined tests and depletion experiments. By these means, a population of lymphocytes with Fc receptors, but lacking SIg (mean 14.6%) was defined and shown to correlate closely with cytotoxic activity for antibody-sensitised target cells. Indirect evidence was also obtained that these lymphocytes, which are regarded as the major population of antibody-dependent cytotoxic cells, are capable of forming rosettes with normal and neuraminidase-treated sheep erythrocytes. The nature of these cells is briefly discussed.

  8. 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.

  9. Kinetics of circulating B lymphocytes in human myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boccadoro, M.; Gavarotti, P.; Fossati, G.; Massaia, M.; Pileri, A.; Durie, B.G.

    1983-04-01

    The tritiated thymidine labeling index (LI%) of peripheral B lymphocytes was studied in eight myeloma patients using simultaneous immunofluorescence and autoradiography. The LI% values were low (0.3%-5.1%), but significantly increased as compared to normal controls. In addition, there was excellent correlation between the LI% values and myeloma disease activity: lowest LI% values were observed in remission patients and the highest at the time of relapse. Simultaneous LI% evaluation of bone marrow myeloma cells in five patients gave concordant results, indicating the same kinetic behavior in both these compartments, particularly in the relapse phase. These data indicate both that circulating B lymphocytes include the neoplastic clone and that these B lymphocytes and bone marrow myeloma cells have similar kinetics.

  10. Herpesvirus sylvilagus infects both B and T lymphocytes in vivo.

    Science.gov (United States)

    Kramp, W J; Medveczky, P; Mulder, C; Hinze, H C; Sullivan, J L

    1985-01-01

    Herpesvirus sylvilagus infection of cottontail rabbits (Sylvilagus floridanus) was studied as a model of herpesvirus-induced lymphoproliferative disorders. Leukocytosis, splenomegaly, proliferation of T cells and virus production by lymphocytes characterized this infectious mononucleosis-like disease. Approximately two copies of circular herpesvirus sylvilagus genomes per cell were detected in spleen cells at 2 weeks postinfection, and circular genomes could still be observed after 4 months. Circular viral genomes were found in both B and T lymphocytes. Small amounts of linear viral DNA (0.1 to 0.3 copies per cell) were also detected in both B and T cells. These results indicated that the virus did not replicate in the majority of lymphocytes in vivo. Herpesvirus sylvilagus infection in cottontail rabbits could be useful as a model for studying the complex virus-host relationships of lymphotropic herpesviruses and perhaps as an animal model for Epstein-Barr virus infection in humans. Images PMID:2993667

  11. The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency.

    Science.gov (United States)

    Partiseti, M; Le Deist, F; Hivroz, C; Fischer, A; Korn, H; Choquet, D

    1994-12-23

    Stimulation of antigen receptors of lymphocytes triggers a transitory release of Ca2+ from internal stores and the opening of a transmembrane Ca2+ conductive pathway. The latter underlies the sustained increase of intracellular free calcium concentration, and it seems to be a key event in the Ca(2+)-dependent biochemical cascade leading to T cell proliferation. Alternatively, pharmacological depletion of internal stores by itself activates Ca2+ influx. This has led to the hypothesis that antigen-triggered Ca2+ influx is secondary to Ca2+ release from internal stores. However, the precise relationship between antigen and Ca2+ release-activated Ca2+ currents remains unclear, particularly since neither of them has been electrophysiologically recorded in normal lymphocytes. Using the whole-cell and the perforated configurations of the patch clamp technique on peripheral blood lymphocytes, we found that a low amplitude Ca(2+)-selective current was triggered when intracellular stores were depleted by stimuli such as the intracellular perfusion of inositol triphosphate or thapsigargin and the extracellular perfusion of ionomycin. A similar current was elicited by the cross-linking of the T cell receptor-CD3 complex. This current displayed an inward rectification below 0 mV and was completely blocked by the divalent cation Cd2+. It was very selective for Ca2+ over Na+ and insensitive to changes in chloride concentration. The physiological relevance of this conductance was investigated with the analysis of abnormal Ca2+ signaling in lymphocytes from a patient suffering from a primary immunodeficiency associated with a defective T cell proliferation. Using fura-2 video imaging, an absence of Ca2+ influx was established in the patient's lymphocytes, whereas the Ca2+ release from internal stores was normal. This was the case whether cells were stimulated physiologically through their antigen receptors or with store depleting pharmacological agents. Most importantly, no Ca(2

  12. The distribution of T lymphocyte subtypes in cases with different chronic liver disease

    Directory of Open Access Journals (Sweden)

    Fulya İlhan

    2013-01-01

    Full Text Available Objective: Hepatitis B is an important infectious disease,which can cause severe chronic cirrhosis and hepatocellularcarcinoma in 1-5 % of adult patients. Whereas, HepatitisD is a defective virus infection that develops in people withHBsAg (+. It has been known that Hepatitis D virus has acytopathic effect but the immune mechanisms which play arole in the development of this disease are still under investigation.Therefore, in this study it was aimed to investigatewhether lymphocytes numbers change in a variety of patientswith chronic hepatitis.Methods: In this study, 22 patients (12 females and 10males with chronic liver diseases were examined. Thesepatients were compared to the control group which consistsof 20 healthy individuals (12 females, 8 males. A flowcytometry assay was conducted to examine T lymphocytesubgroups using CD3, CD4, CD8, CD25, CD56, CD161 andVα24 monoclonal antibodies in peripheral blood samples ofboth patient and control groups.Results: The mean age of patient group and control groupwere 45.87±11.18 and 41.45±7.23 year respectively. TheHbsAg was found to be positive in all patients with the exceptionof one patient. 15 patients also exhibited Anti DeltaAntigen positive as well as HbsAg. Six of these patientshave been diagnosed with chronic liver disease, 7 of themhave been diagnosed liver chrosis and two of them havebeen diagnosed with hepathoma. No difference was foundbetween the patients and healthy controls in terms of totalT lymphocyte, CD4+Th cells CD3+CD56+ NKT cells andVα24+CD161+ iNKT cells. However, the levels of CD8+ Tccells, CD16+56+ NK cells and CD4+CD25+ T lymphocyteswere found to be lower in patients bloods as compared tothe healthy controls.Conclusions: These results suggest that HbsAg positivitymay cause the decreases of the cells which are responsiblefor cytotoxic response. Nevertheless, further studiesare required to explain the immunological response to thechronic hepatitis.Key words: Chronic hepatitis

  13. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  14. Increased Fas and Bcl-2 expression on peripheral blood T and B lymphocytes from juvenile-onset systemic lupus erythematosus, but not from juvenile rheumatoid arthritis and juvenile dermatomyositis.

    Science.gov (United States)

    Liphaus, Bernadete L; Kiss, Maria H B; Carrasco, Solange; Goldenstein-Schainberg, Claudia

    2006-01-01

    Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal-Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  15. Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bernadete L. Liphaus

    2006-01-01

    Full Text Available Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE, juvenile rheumatoid arthritis (JRA and juvenile dermatomyositis (JDM. Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  16. Changes of lymphocyte beta-adrenergic receptors after surgical stress.

    Science.gov (United States)

    Eandi, M; Buraglio, M; Arduino, C; Viano, I; Sansalvadore, G; Arbinolo, M A

    1984-01-01

    In this study the authors' purpose was to observe the effects of surgical stress on the number of lymphocyte beta-adrenergic receptors in hypertensive and normotensive subjects. It was noticed that after surgery a significant reduction occurred in the number of binding sites of lymphocytes of both hypertensive and normotensive subjects. The time course of recovery to the pre-operative values of binding sites varied between the two groups, being slower in normotensive than in hypertensive patients. This might suggest a different pattern of regulation of the beta-adrenergic receptor between hypertensive and normotensive subjects.

  17. Lymphocyte fluorescent profiles (LFP): a possible screening technique in neoplasia.

    Science.gov (United States)

    Love, L A; Metcalf, N F; Metcalf, W K; Sharp, J G

    1979-05-01

    A technique involving fluorescent protein staining and microfluorometry has been developed for measuring the lymphocyte fluorescent profile (LFP) of peripheral blood lymphocytes. In contrast to normal humans who display a regular bell-shaped curve, the profile from patients with cancer is irregular, showing a bimodal distribution of fluorescence, with a significant population of cells fluorescing at a higher relative intensity. It is suggested that this elevation in protein concentration is due to an immune response to the presence of a neoplasm, and thus this technique may prove to be a useful indicator of malignancy.

  18. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

    DEFF Research Database (Denmark)

    Tenzer, Stefan; Wee, Edmund; Burgevin, Anne

    2009-01-01

    Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated ......Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group...

  19. Effect of oral proguanil on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    In vitro studies have indicated that the antifolates pyrimethamine [4, 6] and cycloguanil (the active metabolite of proguanil) suppress the proliferation of stimulated human lymphocytes; proguanil has no effect [2]. During the early growth phase of the cells, 14C-thymidine (14C-TdR) incorporation...... on human lymphocytes, the present study was undertaken. Little information is available about the serum levels of proguanil and cycloguanil following ingestion of prophylactic doses [8]. Therefore, the serum concentrations of proguanil and cycloguanil were estimated, to allow comparison with previous...

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

    Directory of Open Access Journals (Sweden)

    Agrawal Sudhanshu

    2005-08-01

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

  1. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Bernard, S M; Bird, C C; Darwin, C M; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-07-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

  2. Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    Neelam Siddiqui; Saeed Al-Amoudi; Aamer Aleem; Maha Arafah; Layla Al-Gwaiz

    2008-01-01

    Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.

  3. Chronic lymphocytic-leukemia with pleomorphic lymphocytes (cll-pleo) - a comparative-study with typical cll.

    Science.gov (United States)

    Batata, A; Shen, B; Batata, S

    1994-05-01

    Cell suspensions from the peripheral brood of 21 cases of chronic lymphocytic leukemia with pleomorphic lymphocytes (CLL-pleo) and 155 cases of typical CLL were analyzed to define the phenotype of the former and compare it with the phenotype of the latter. CLL-pleo was characterized by weak fluorescence intensity of surface immunoglobulin (mean channel number on flow cytometry <200), positive mouse rosettes and CD5, and negative CD22 and tartrate resistant acid phosphatase. Comparison of the positive rates of the markers and of the mean percentages of marker-expressing cells showed no statistical difference between CLL-pleo and typical CLL. CLL-pleo constitutes a morphological variant of typical CLL bearing the same membrane phenotype as typical CLL, although the mean absolute lymphocyte count in CLL-pleo was significantly higher than that of typical CLL.

  4. Selecting the best defect reduction methodology

    Energy Technology Data Exchange (ETDEWEB)

    Hinckley, C.M. [Sandia National Labs., Albuquerque, NM (United States); Barkan, P. [Stanford Univ., CA (United States)

    1994-04-01

    Defect rates less than 10 parts per million, unimaginable a few years ago, have become the standard of world-class quality. To reduce defects, companies are aggressively implementing various quality methodologies, such as Statistical Quality Control Motorola`s Six Sigma, or Shingo`s poka-yok. Although each quality methodology reduces defects, selection has been based on an intuitive sense without understanding their relative effectiveness in each application. A missing link in developing superior defect reduction strategies has been a lack of a general defect model that clarifies the unique focus of each method. Toward the goal of efficient defect reduction, we have developed an event tree which addresses a broad spectrum of quality factors and two defect sources, namely, error and variation. The Quality Control Tree (QCT) predictions are more consistent with production experience than obtained by the other methodologies considered independently. The QCT demonstrates that world-class defect rates cannot be achieved through focusing on a single defect source or quality control factor, a common weakness of many methodologies. We have shown that the most efficient defect reduction strategy depend on the relative strengths and weaknesses of each organization. The QCT can help each organization identify the most promising defect reduction opportunities for achieving its goals.

  5. Population Pharmacokinetics of Ofatumumab in Patients With Chronic Lymphocytic Leukemia, Follicular Lymphoma, and Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Struemper, Herbert; Sale, Mark; Patel, Bela R;

    2014-01-01

    Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma...

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

    Science.gov (United States)

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

    2001-12-01

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

  7. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  8. The imbalance of helper T lymphocytes and cytotoxic T lymphocytes in acute renal transplantation rejection

    Institute of Scientific and Technical Information of China (English)

    YAN JIANG; ZHI QIN TANG; LIN PENG; YU LIANG WANG; ZHI PING WANG

    2007-01-01

    To investigate the imbalance state of helper T lymphocytes (Th) and cytotoxic T lymphocytes (Tc) and the roles of Th1/Th2/Th3 and Tc1/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis,while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Th1, Th2 and Th3 cells were (10.45±8.15)%, (5.05±4.15)% and (3.90±3.21)%,and those of Tc1 and Tc2 cells were (9.83±7.03)% and (4.51±2.17)%, respectively. However,the percentages of Th1 and Tc1 cells in peripheral blood of the stable recipients after transplantation were (7.29±5.62)% and (7.04±5.15)%, showing definite reduction, while those of Th2, Th3and Tc2 cells showed significant increase, (6.34±5.67)%, (4.94±4.14) % and ( 6.86 ±4.42) %, respectively. In case of recipients with acute rejection, the percentages of Th1 and Tc1 cells appeared to be (18.55±13.21)% and (15.84±11.72)%, also showing significant increase, but those of Th2,Th3 and Tc2 cells appeared to be reduced, (4.19±3.62)%, (3.02±2.83)% and (3.88±1.63) %, respectively. Significant differences could be detected among these three groups (P <0.05). The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients (2.24±0.59 vs 1.95±0.45), but that of the stable recipients and healthy controls (1.98±0.31 )showed no any significant difference. From the above observation, it is evident that imbalance between Th1, Th2 and Th3 with Te1 and Tc2 cells may exist after renal transplantation and probably, the immune imbalance may be induced through the secretion of cytokines INF-γ by Th1 or Te1 cells , I1-4 by Th2 and Tc2 cells and TGF-β by Th3.

  9. The peripheral blood compartment in patients with Graves' disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes

    Science.gov (United States)

    Van der Weerd, K; Van Hagen, P M; Schrijver, B; Kwekkeboom, D J; De Herder, W W; Ten Broek, M R J; Postema, P T E; Van Dongen, J J M; Staal, F J T; Dik, W A

    2013-01-01

    Graves' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)+ and CD25+] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38highCD27−, P < 0·03) and pre-naive mature (CD38lowCD27−IgD+CD5+, P < 0·04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5+, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5+ B lymphocytes within the peripheral blood. The increase in CD5+ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5+ B lymphocytes. PMID:23901889

  10. Subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carcinoma: a case report

    OpenAIRE

    Choi Young Sik; Han You Jin; Yeo Go Eun; Kwon Su Kyoung; Kim Bu Kyung; Park Yo-Han; Kim Sung Won; Chun Bong Kwon; Kong Eun Hee; Kim Jeong Hoon

    2013-01-01

    Abstract Introduction Subacute lymphocytic thyroiditis is anautoimmune thyroid disease presenting with transient thyrotoxicosis as well as transient hypothyroidism. Several factors have been thought to be the initiating event in subacute lymphocytic thyroiditis. However, subacute lymphocytic thyroiditis that develops after thyroid lobectomy has not yet been reported in the literature. We report a case of subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carc...

  11. Electronic Defect States in Polyaniline.

    Science.gov (United States)

    Ginder, John Matthew

    The electronic defect states of the conducting polymer polyaniline are studied by a variety of magnetic and optical techniques. The insulating emeraldine base form (EB) of polyaniline can be converted to the conducting emeraldine salt form (ES) by treatment with aqueous acids such as HCl. This "protonic acid doping" process occurs via the bonding of protons to the polymer chain, without altering the number of chain electrons. Magnetic susceptibility studies reveal that a roughly linear growth of the Pauli paramagnetic susceptibility, and an increase in the density of Curie-like spins, accompanies this conversion. Consequently, the protonation-induced defects are mainly spin-1/2 polarons; further, the linear growth of the Pauli susceptibility suggests that fully protonated regions--metallic islands --grow with increasing doping level. The electronic structure of the metallic phase is proposed to be that of a polaron lattice with electronic bandwidth ~0.4 eV and polaron decay length ~2 A. The defects which accomodate excess charge in EB were also studied by near-steady-state photoinduced absorption experiments. Upon photoexcitation into the 2 eV absorption band in EB, several photoinduced features evolved. Induced bleachings of the existing transitions at 2.0 and 3.7 eV were observed; induced absorptions were found at 0.9, 1.4, and 3.0 eV. The 2.0 eV bleaching is consistent with the production of molecular charge-transfer excitons, which may relax to a different ring conformation causing long-lived bleaching, or to two separate charges on a single chain. Indeed, the induced absorptions at 1.4 and 3.0 eV are, by analogy with similar protonation -induced absorptions and by their bimolecular recombination kinetics, assigned to photoexcited polarons. Light-induced electron spin resonance experiments confirm the presence of photogenerated spins upon pumping into the excitonic absorption. Near-steady-state photoconductivity measurements on EB reveal a very small induced

  12. Atomic Approaches to Defect Thermochemistry

    Science.gov (United States)

    1992-04-30

    ATOMIC APPROACHES TO DEFECT THERMOCHEMISTRY (AFOSR-89-0309) for period 1 April 1989 to 31 March 1992 Submitted by Professor James A. Van Vechten and...could be very much less. Thus, the GaAs lattice is indeed found to be stiff. Positron annihilation experiments (17) also teach us that GaAs samples...to be less for Si than for Ge. Experience with chemical trends of bond strengths, as well as the empirical literature, teach us that the H bond

  13. Developmental defects of the lungs

    Energy Technology Data Exchange (ETDEWEB)

    DaCosta, H.; Pathak, A.; Noronha, O.; Dalal, S.; Shah, K.; Merchant, S.

    1981-06-01

    Poor lung development was first noted on scintigraphy using sup(99m)Tc-phytate in 32 children. They had all been referred for a hepatosplenic scan but the initial circulatory phase of the radiopharmaceutical was also recorded as a routine procedure. In 3 patients it revealed aplasia of an entire lung; bilateral pulmonary hypolplasia was observed in 14 of 16 patients with diaphragmatic herniae. Six patients with congenital heart enlargement showed a poorly developed ipsilateral lung; 5 of 6 patients with dextrocardia without an intracardiac defect had a larger left lung compared with the right lung; both pulmonary beds appeared equal in a patient with mesocardia.

  14. Individual radiosensitivity does not correlate with radiation-induced apoptosis in lymphoblastoid cell lines or CD{sup 3+} lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wistop, A.; Keller, U.; Grabenbauer, G.G.; Sauer, R.; Distel, L.V.R. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg, Erlangen (Germany); Sprung, C.N. [Div. of Research, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)

    2005-05-01

    Background and purpose: spontaneous and radiation-induced apoptosis of lymphoblastoid cell lines (LCLs) derived from healthy donors, cancer patients and donors with radiosensitivity syndromes as well as CD{sup 3+} lymphocytes from patients with {>=} grade 3 late toxicity were investigated as a possible marker for the detection of individual radiosensitivity. These investigations are based on the hypothesis that hypersensitive patients have reduced levels of apoptosis after in vitro irradiation as a result of a defect in the signaling pathway. Material and methods: Epstein-Barr virus-(EBV-)transformed LCLs derived from five healthy donors, seven patients with heterozygous or homozygous genotype for ataxia-telangiectasia or Nijmegen breakage syndrome and five patients with {>=} grade 3 late toxicity (RTOG) were investigated. In addition, CD{sup 3+} lymphocytes from 21 healthy individuals and 18 cancer patients including five patients with a proven cellular hypersensitivity to radiation were analyzed. Cells were irradiated in vitro with a dose of 2 and 5 Gy and were incubated for 48 h. Apoptotic rates were measured by the TUNEL assay followed by customized image analysis. Results: four out of seven radiosensitivity syndrome patients were identified to have an increased cellular radiosensitivity as determined by reduced apoptotic rates after irradiation of their respective LCLs. Comparatively, only two of the five hypersensitive cancer patients were clearly identified by reduced apoptotic rates. Spontaneous apoptotic rates were very homogeneous among all 39 samples from controls and patients, while lymphocytes of all cancer patients showed significantly lower radiation-induced rates. Conclusion: only a subgroup of hypersensitive patients may be identified by reduction of radiation-induced apoptotic rate. It is concluded that the hypothesis according to which hypersensitive cells have reduced levels of apoptosis is only conditionally true. The authors suggest that this

  15. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Science.gov (United States)

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y; Gryaznov, Sergei M; Johnston, James B; Lees-Miller, Susan P; Assouline, Sarit E; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  16. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Directory of Open Access Journals (Sweden)

    May Shawi

    Full Text Available We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR, can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1 if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2 the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  17. Signaling lymphocyte activating molecule (SLAM) expression in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Piskin, A Kevser; Akpinar, Pinar; Muftuoglu, Sevda; Anlar, Banu

    2007-08-01

    Signaling lymphocyte activating molecule (SLAM) is a receptor for measles virus which also has immunomodulatory activity. We analyzed SLAM expression in mononuclear cells (MNC) of patients with SSPE (n=7) and control subjects (n=7) from the same population. Native 10% PAGE analysis in cell and brain tissue extracts followed by Western blotting using monoclonal anti-human SLAM showed four types of bands. Differences in the type and amount of SLAM expression were observed between SSPE and control cases. Lymphocytes of SSPE patients showed two types of SLAM bands in comparison to only one in control lymphocytes. Stimulation of cells with lipopolysaccharide (80 u/ml) and concanavalin A (1 microg/ml) in vitro led to the appearance of a second isoform in both groups. Brain homogenates of SSPE patients (n=2) displayed all four types of SLAM isoforms at significantly higher levels than those of control brains (n=2). Our results show native PAGE enables the detection of all SLAM isotypes. The expression of SLAM is increased in lymphocytes, monocytes, and brain tissues of SSPE patients.

  18. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo

    2014-01-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

  19. Association of lymphocytic colitis and lactase deficiency in pediatric population.

    Science.gov (United States)

    Sun, Jihong; Lin, Jingmei; Parashette, Kalayan; Zhang, Jianjun; Fan, Rong

    2015-02-01

    Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.

  20. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker

    2012-01-01

    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...

  1. Effects of a Simulated Tennis Match on Lymphocyte Subset Measurements

    Science.gov (United States)

    Schafer, Mark; Kell, Holly; Navalta, James; Tibana, Ramires; Lyons, Scott; Arnett, Scott

    2014-01-01

    Tennis is an activity requiring both endurance and anaerobic components, which could have immunosuppressive effects postexercise. Purpose: The purpose of this investigation was to determine the effect of a simulated tennis match on apoptotic and migratory markers on lymphocyte subsets. Method: Male high school (n = 5) and college (n = 3) tennis…

  2. Paraneoplastic pemphigus as the initial presentation of chronic lymphocytic leukemia

    NARCIS (Netherlands)

    van Mook, WNKA; Fickers, MMF; Theunissen, PHMH; vander Kley, JAMJ; Duijvestijn, JA; Pas, HH; Flikweert, DC

    2001-01-01

    The case history of a 61-year-old male patient is described, who presented with severe stomatitis, conjunctivitis and leukocytosis. The diagnosis chronic lymphocytic leukemia (CLL) stage A (0) was made, for which no treatment was necessary. Progression of stomatitis and conjunctivitis and erythosqua

  3. Langerhans cells and subsets of lymphocytes in the nasal mucosa

    DEFF Research Database (Denmark)

    Hellquist-Dahl, B; Olsen, K E; Irander, K;

    1991-01-01

    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...

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

    Directory of Open Access Journals (Sweden)

    Beenish A. Majeed

    2015-08-01

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

  5. Increased circulating apoptotic lymphocytes in children with Down syndrome

    NARCIS (Netherlands)

    Gemen, E.F.A.; Verstegen, R.H.J.; Leuvenink, J.; Vries, E. de

    2012-01-01

    Down syndrome (DS) resembles immunodeficiency with increased infections, auto-immune diseases, and hematological malignancies. Until now, immunological studies in DS mainly focused on T-lymphocytes. We recently described a profound B-lymphocytopenia in children with DS. This could be caused by incre

  6. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard;

    1999-01-01

    To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... controlled infection and limited tissue damage. Thus, the presence or absence of IFN-gamma determines whether CTLs will clear infection with this noncytopathogenic virus or induce severe immunopathology....

  7. Growing B Lymphocytes in a Three-Dimensional Culture System

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

    A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing

  8. Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes

    Science.gov (United States)

    Marañón, Concepción; Desoutter, Jean-François; Hoeffel, Guillaume; Cohen, William; Hanau, Daniel; Hosmalin, Anne

    2004-04-01

    A better understanding of the antigen presentation pathways that lead to CD8+ T cell recognition of HIV epitopes in vivo is needed to achieve better immune control of HIV replication. Here, we show that cross-presentation of very small amounts of HIV proteins from apoptotic infected CD4+ T lymphocytes by dendritic cells to CD8+ T cells is much more efficient than other known HIV presentation pathways, i.e., direct presentation of infectious virus or cross-presentation of defective virus. Unexpectedly, dendritic cells also take up actively antigens into endosomes from live infected CD4+ T lymphocytes and cross-present them as efficiently as antigens derived from apoptotic infected cells. Moreover, live infected CD4+ T cells costimulate cross-presenting dendritic cells in the process. Therefore, dendritic cells can present very small amounts of viral proteins from infected T cells either after apoptosis, which is frequent during HIV infection, or not. Thus, if HIV expression is transiently induced while costimulation is enhanced (for instance after IL-2 and IFN immune therapy), this HIV antigen presentation pathway could be exploited to eradicate latently infected reservoirs, which are poorly recognized by patients' immune systems.

  9. A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes.

    Science.gov (United States)

    Kim, Gisen; Shinnakasu, Ryo; Saris, Christiaan J M; Cheroutre, Hilde; Kronenberg, Mitchell

    2013-02-15

    IL-27, an IL-12 family cytokine, has pleiotropic functions in the differentiation and expansion of CD4(+) T cell subsets. In this study, we discovered a novel function of IL-27. CD4(+)CD45RB(high) T cells from mice deficient for the α-chain of IL-27 receptor failed to induce colitis in Rag(-/-) recipients, because of an inability of activated donor cells to survive. Interestingly, IL-27 was indispensable for the prevention of colitis by regulatory T cells, also because of a defect in long-term cell survival. IL-27 affected the survival of activated T lymphocytes, rather than promoting cell proliferation, by inhibiting Fas-mediated activation-induced T cell death, acting through the STAT3 signaling pathway. The addition of IL-27 during activation resulted in an increased cell number, which was correlated with decreased activation of both caspases 3 and 8. This prosurvival effect was attributed to downregulation of FasL and to the induction of the antiapoptotic protein cFLIP. Although activation induced cell death is an important mechanism for the maintenance of immunological homeostasis, protection of lymphocytes from excessive cell death is essential for effective immunity. Our data indicate that IL-27 has a crucial role in the inhibition of activation-induced cell death, thereby permitting Ag-driven T cell expansion.

  10. File list: ALL.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.T-Lymphocytes hg19 All antigens Blood T-Lymphocytes SRX1425818,SRX...8 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.T-Lymphocytes.bed ...

  11. File list: Unc.Bld.10.AllAg.Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Lymphocytes hg19 Unclassified Blood Lymphocytes SRX118080,SRX27708...1,SRX118079 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Lymphocytes.bed ...

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

    DEFF Research Database (Denmark)

    Hagdrup, H; Tønnesen, E; Clemmensen, O

    1992-01-01

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

  13. Suppression of lymphocyte proliferation by parainfluenza virus type 3-infected bovine alveolar macrophages.

    Science.gov (United States)

    Basaraba, R J; Brown, P R; Laegreid, W W; Silflow, R M; Evermann, J F; Leid, R W

    1993-06-01

    Lymphocytes stimulated with concanavalin A (Con A) or antigen in the presence of bovine parainfluenza virus type 3 (PIV-3) infected bovine alveolar macrophages (BAM) or monocytes, had depressed [3H]thymidine incorporation. This failure of lymphocytes to incorporate radiolabel required live virus, was time dependent and was most pronounced when BAM were infected for 48 hr prior to the addition of lymphocytes. The rate of infection of alveolar macrophages and the release of infectious virus into culture supernatants paralleled suppression of lymphocyte mitogenesis by PIV-3. However, the peak titre of exogenous, live or inactivated virus was not suppressive when added to lymphocyte macrophage cultures just prior to Con A stimulation. Neither the loss of viable alveolar macrophages nor a shift in antigen or mitogen dose response in virally infected cultures could account for the deficit in [3H]thymidine incorporation by lymphocytes. Despite the presence of lymphocyte-associated virus antigen detected by direct immunofluorescence, no increase in PIV-3 titre above baseline was seen from infected lymphocytes, irrespective of mitogen stimulation. Likewise, lymphocytes did not contribute to the extracellular virus pool in lymphocyte-macrophage cultures as the increases in viral titre above basal levels in supernatants were equal to levels released by macrophages alone. The expression of viral antigen on lymphocytes stimulated in the presence of PIV-3-infected BAM suggests a non-productive or abortive infection of lymphocytes mediated through contact with infected macrophages.

  14. File list: DNS.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.T-Lymphocytes,_Regulatory mm9 DNase-seq Blood T-Lymphocytes, Regula...tory SRX188661,SRX191058 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.10.AllAg.T-Lymphocytes,_Regulatory.bed ...

  15. File list: His.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.T-Lymphocytes,_Regulatory mm9 Histone Blood T-Lymphocytes, Regulat...ory http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.T-Lymphocytes,_Regulatory.bed ...

  16. File list: His.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.T-Lymphocytes,_Regulatory mm9 Histone Blood T-Lymphocytes, Regulat...ory http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.T-Lymphocytes,_Regulatory.bed ...

  17. File list: His.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.T-Lymphocytes,_Regulatory hg19 Histone Blood T-Lymphocytes, Regula...tory http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.T-Lymphocytes,_Regulatory.bed ...

  18. File list: Unc.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.T-Lymphocytes,_Regulatory hg19 Unclassified Blood T-Lymphocytes, Regula...tory http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.T-Lymphocytes,_Regulatory.bed ...

  19. File list: Unc.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.T-Lymphocytes,_Regulatory mm9 Unclassified Blood T-Lymphocytes, Regula...tory http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.T-Lymphocytes,_Regulatory.bed ...

  20. File list: His.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  2. File list: DNS.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  3. File list: Unc.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Oth.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: ALL.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  6. File list: Oth.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Unc.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  8. File list: ALL.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  9. File list: Unc.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

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  10. File list: Pol.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: His.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: His.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Oth.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Unc.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Pol.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: His.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Oth.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: DNS.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: ALL.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Oth.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Oth.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: DNS.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: DNS.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: DNS.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: DNS.Bld.20.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: ALL.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Bld.50.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Unc.Bld.10.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Pol.Bld.05.AllAg.T-Lymphocytes,_Regulatory [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Bld.05.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Oth.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: NoD.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Oth.Bld.05.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: ALL.Bld.05.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Bld.05.AllAg.Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: DNS.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Unc.Bld.20.AllAg.Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: ALL.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: DNS.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: DNS.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: ALL.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Unc.Bld.50.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: InP.Bld.05.AllAg.T-Lymphocytes [Chip-atlas[Archive

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  10. File list: InP.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: ALL.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Bld.05.AllAg.Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Pol.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: His.Bld.10.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

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  16. File list: Oth.Bld.10.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: ALL.Bld.50.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: InP.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Unc.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  1. File list: InP.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: His.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: DNS.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Pol.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: ALL.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: InP.Bld.50.AllAg.T-Lymphocytes [Chip-atlas[Archive

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  8. File list: His.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Unc.Bld.10.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  11. File list: ALL.Bld.10.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: InP.Bld.10.AllAg.T-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  14. File list: Oth.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Pol.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: NoD.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. Defect in lectin-induced interleukin 2 production by peripheral blood lymphocytes of patients with invasive urinary bladder carcinoma

    DEFF Research Database (Denmark)

    Bubeník, J; Kieler, J; Tromholt, V

    1988-01-01

    The production of interleukin 2 (IL-2) by phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 21 patients with transitional cell carcinoma of the urinary bladder (BTCC) and 16 control blood donors was measured with a solid phase enzyme immunoassay based on the dual...

  18. Long intergenic noncoding RNAs: novel drivers of human lymphocyte differentiation

    Directory of Open Access Journals (Sweden)

    Ilaria ePanzeri

    2015-04-01

    Full Text Available Upon recognition of a foreign antigen, CD4+ naïve T lymphocytes proliferate and differentiate into subsets with distinct functions. This process is fundamental for the proper immune system function, as CD4+ T cells orchestrate both the innate and adaptive immune response. Traditionally, this differentiation event has been regarded as the acquisition of an irreversible cell fate so that memory and effector CD4+ T subsets were considered terminally differentiated cells or lineages. Consequently, these lineages are conventionally defined thanks to their prototypical set of cytokines and transcription factors. However, recent findings suggest that CD4+ T lymphocytes possess a remarkable phenotypic plasticity, as they can often redirect their functional program depending on the milieu they encounter. Therefore new questions are now compelling such as which are the molecular determinants underlying plasticity and stability and how the balance between these two opposite forces drives the cell fate. As already mentioned, in some cases the mere expression of cytokines and master regulators could not fully explain lymphocytes plasticity. We should consider other layers of regulation, including epigenetic factors such as the modulation of chromatin state or the transcription of noncoding RNAs, whose high cell-specificity give a hint on their involvement in cell fate determination. In this review, we will focus on the recent advances in understanding CD4+ T lymphocytes subsets specification from an epigenetic point of view. In particular, we will emphasize the emerging importance of noncoding RNAs as key players in these differentiation events. We will also present here new data from our laboratory highlighting the contribution of long noncoding RNAs in driving human CD4+ T lymphocytes differentiation.

  19. Utility of DF-1 for Radioprotection in Lymphocytes

    Science.gov (United States)

    Reynolds, Julia; Casey, Rachael; Wu, Honglu; Huff, Janice; Emami, Kamal; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar

  20. Inspection of directed self-assembly defects

    Science.gov (United States)

    Ito, Chikashi; Durant, Stephane; Lange, Steve; Harukawa, Ryota; Miyagi, Takemasa; Nagaswami, Venkat; Rincon Delgadillo, Paulina; Gronheid, Roel; Nealey, Paul

    2014-03-01

    Directed Self-Assembly (DSA) is considered as a potential patterning solution for future generation devices. One of the most critical challenges for translating DSA into high volume manufacturing is to achieve low defect density in the DSA patterning process. The defect inspection capability is fundamental to defect reduction in any process, particularly the DSA process, as it provides engineers with information on the numbers and types of defects. While the challenges of other candidates of new generation lithography are well known (for example, smaller size, noise level due to LER etc.), the DSA process causes certain defects that are unique. These defects are nearly planar and in a material which produces very little defect scattering signal. These defects, termed as "dislocation" and "disclination" have unique shapes and have very little material contrast. While large clusters of these unique defects are easy to detect, single dislocation and disclination defects offer considerable challenge during inspection. In this investigation, etching the DSA pattern into a silicon (Si) substrate structure to enhance defect signal and Signal-to-Noise Ratio (SNR) is studied. We used a Rigorous Coupled-Wave Analysis (RCWA) method for solving Maxwell's equations to simulate the DSA unique defects and calculate inspection parameters. Controllable inspection parameters include various illumination and collection apertures, wavelength band, polarization, noise filtering, focus, pixel size, and signal processing. From the RCWA simulation, we compared SNR between "Post-SiN etch" and "Post-SiN+Si-substrate etch" steps. The study is also extended to investigate wafer-level data at post etch inspection. Both the simulations and inspection tool results showed dramatic signal and SNR improvements when the pattern was etched into the SiN+Si substrate allowing capture of DSA unique defect types.

  1. CLONAL CHRONIC LYMPHOCYTIC LEUKEMIA-LIKE B-LYMPHOCYTES IN THE BLOOD OF PATIENTS WITH CUTANEOUS T-CELL DISORDERS

    NARCIS (Netherlands)

    DAENEN, S; VADER, PCV; BLOM, N; PIETENS, J; HOLLEMA, H; SMIT, JW

    1993-01-01

    A population of B cells with characteristics of chronic lymphocytic leukaemia was found in the peripheral blood of four patients who presented with cutaneous infiltration of atypical CD4+ T cells with cerebriform nuclei. The B cells had a low density of immunoglobulin on their surface membrane, expr

  2. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: are they useful for predicting gestational diabetes mellitus during pregnancy?

    Directory of Open Access Journals (Sweden)

    Sargın MA

    2016-04-01

    Full Text Available Mehmet Akif Sargın, Murat Yassa, Bilge Dogan Taymur, Ayhan Celik, Emrah Ergun, Niyazi Tug Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey Objective: We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR could be utilized to screen for gestational diabetes mellitus (GDM.Subjects and methods: NLR and PLR were assessed by retrospective analysis of 762 healthy and pregnant women with GDM. The patients were stratified into four groups, as follows: GDM (n=144, impaired glucose tolerance (n=76, only screen positive (n=238, and control (n=304.Results: The leukocyte, neutrophil, and lymphocyte counts were significantly higher in the study groups compared with the control group (P=0.001; P<0.01. There were no statistically significant differences between the groups with respect to the NLR and PLR (P>0.05.Conclusion: We do not recommend that blood NLR and PLR can be used to screen for GDM. However, increase in the leukocyte count is an important marker for GDM as it provides evidence of subclinical inflammation. Keywords: inflammation, lymphocytes, neutrophils, platelets, pregnancy

  3. Effects of in-cascade defect clustering on near-term defect evolution

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-08-01

    The effects of in-cascade defect clustering on the nature of the subsequent defect population are being studied using stochastic annealing simulations applied to cascades generated in molecular dynamics (MD) simulations. The results of the simulations illustrates the strong influence of the defect configuration existing in the primary damage state on subsequent defect evolution. The large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades have been shown to be significant factors affecting the evolution of the defect distribution. In recent work, the effects of initial cluster sizes appear to be extremely important.

  4. Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib

    Directory of Open Access Journals (Sweden)

    Koh Okamoto

    2016-01-01

    Full Text Available Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. It acts by inhibiting Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton’s tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

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

    Directory of Open Access Journals (Sweden)

    Mie Oki

    2011-01-01

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

  6. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  7. GENOMIC PROFILING BY MULTIPLEX LIGATION - DEPENDENT PROBE AMPLIFICATION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Georgiana-Emilia Grigore

    2013-11-01

    Full Text Available The clinical management of severe pathological conditions, such as B-cell chronic lymphocytic leukemia (B-CLL, is subject to continuous optimization and re-evaluation. Patients may fully benefit from rapid, standardized laboratory tools designed to facilitate their early stratification according to disease risk, stage and prognosis. Such technologies may also aid the clinician in selecting the therapeutic option with the greatest chances of success. The presence of specific genetic abnormalities are frequently associated with the clinical outcome of oncologic patients in general, and B-CLL patients in particular. In the current study, a group of 58 B-CLL patients were evaluated for the detection of gene copy number alterations (deletions or duplication/ amplifications within 45 distinct genetic targets, by means of a novel molecular methodology, Multiplex Ligation - Dependent Probe Amplification (MLPA. Simple or complex genetic defects were identified in 67% of cases, and the most common aberrations observed were: deletion of the short arm of chromosome 13 in 33% of cases, deletion of the long arm of chromosome 11 in 16% of cases, trisomy 12 in 16% of cases, and deletion of the short arm of chromosome 17 in 7% of cases. The main conclusion of the study presented here points towards MLPA as a potential key step of clinical management protocols in B-CLL, providing that it will be fully standardised for routine diagnosis.

  8. The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice.

    Science.gov (United States)

    Fukuhara, Shigetomo; Simmons, Szandor; Kawamura, Shunsuke; Inoue, Asuka; Orba, Yasuko; Tokudome, Takeshi; Sunden, Yuji; Arai, Yuji; Moriwaki, Kazumasa; Ishida, Junji; Uemura, Akiyoshi; Kiyonari, Hiroshi; Abe, Takaya; Fukamizu, Akiyoshi; Hirashima, Masanori; Sawa, Hirofumi; Aoki, Junken; Ishii, Masaru; Mochizuki, Naoki

    2012-04-01

    The bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) promotes the egress of newly formed T cells from the thymus and the release of immature B cells from the bone marrow. It has remained unclear, however, where and how S1P is released. Here, we show that in mice, the S1P transporter spinster homolog 2 (Spns2) is responsible for the egress of mature T cells and immature B cells from the thymus and bone marrow, respectively. Global Spns2-KO mice exhibited marked accumulation of mature T cells in thymi and decreased numbers of peripheral T cells in blood and secondary lymphoid organs. Mature recirculating B cells were reduced in frequency in the bone marrow as well as in blood and secondary lymphoid organs. Bone marrow reconstitution studies revealed that Spns2 was not involved in S1P release from blood cells and suggested a role for Spns2 in other cells. Consistent with these data, endothelia-specific deletion of Spns2 resulted in defects of lymphocyte egress similar to those observed in the global Spns2-KO mice. These data suggest that Spns2 functions in ECs to establish the S1P gradient required for T and B cells to egress from their respective primary lymphoid organs. Furthermore, Spns2 could be a therapeutic target for a broad array of inflammatory and autoimmune diseases.

  9. Primordial inhomogeneities from massive defects during inflation

    Science.gov (United States)

    Firouzjahi, Hassan; Karami, Asieh; Rostami, Tahereh

    2016-10-01

    We consider the imprints of local massive defects, such as a black hole or a massive monopole, during inflation. The massive defect breaks the background homogeneity. We consider the limit that the physical Schwarzschild radius of the defect is much smaller than the inflationary Hubble radius so a perturbative analysis is allowed. The inhomogeneities induced in scalar and gravitational wave power spectrum are calculated. We obtain the amplitudes of dipole, quadrupole and octupole anisotropies in curvature perturbation power spectrum and identify the relative configuration of the defect to CMB sphere in which large observable dipole asymmetry can be generated. We observe a curious reflection symmetry in which the configuration where the defect is inside the CMB comoving sphere has the same inhomogeneous variance as its mirror configuration where the defect is outside the CMB sphere.

  10. Primordial inhomogeneities from massive defects during inflation

    CERN Document Server

    Firouzjahi, Hassan; Rostami, Tahereh

    2016-01-01

    We consider the imprints of local massive defects, such as a black hole or a massive monopole, during inflation. The massive defect breaks the background homogeneity. We consider the limit that the physical Schwarzschild radius of the defect is much smaller than the inflationary Hubble radius so a perturbative analysis is allowed. The inhomogeneities induced in scalar and gravitational wave power spectrum are calculated. We obtain the amplitudes of dipole, quadrupole and octupole anisotropies in curvature perturbation power spectrum and identify the relative configuration of the defect to CMB sphere in which large observable dipole asymmetry can be generated. We observe a curious reflection symmetry in which the configuration where the defect is inside the CMB comoving sphere has the same inhomogeneous variance as its mirror configuration where the defect is outside the CMB sphere.

  11. Little String Origin of Surface Defects

    CERN Document Server

    Haouzi, Nathan

    2016-01-01

    We derive the codimension-two defects of 4d $\\mathcal{N} = 4$ Super Yang-Mills (SYM) theory from the (2, 0) little string. The origin of the little string is type IIB theory compactified on an ADE singularity. The defects are D-branes wrapping the 2-cycles of the singularity. We use this construction to make contact with the description of SYM defects due to Gukov and Witten [arXiv:hep-th/0612073]. Furthermore, we derive from a geometric perspective the complete nilpotent orbit classification of codimension-two defects, and the connection to ADE-type Toda CFT. The only data needed to specify the defects is a set of weights of the algebra obeying certain constraints, which we give explicitly. We highlight the differences between the defect classification in the little string theory and its (2, 0) CFT limit.

  12. FABRIC DEFECT DETECTION USING STEERABLE PYRAMID

    Directory of Open Access Journals (Sweden)

    S. Mythili

    2011-05-01

    Full Text Available In this paper, a novel idea is proposed for fabric defect detection. De- fects are detected in the fabric using steerable pyramid along with a defect detection algorithm. Various steerable pyramid of four size 256*256, 128*128, 64*64, 32*32 and with four orientation bands 00,450, 900, 1350 are used. Utilizing a Steerable pyramid proved ade- quate in the representation of fabric images in multi-scale and multi- orientations; thus allowing defect detection algorithms to run more effectively. Defect detection algorithm identifies and locates the im- perfection in the defective sample using the statistics mean and stan- dard deviation. This statistics represents the relative amount of inten- sity in the texture and is sufficient to measure defects in the current model .The obtained result are compared with the existing methods wavelet based system and with Gaussian and Laplacian pyramid.

  13. Surface defects and temperature on atomic friction

    Energy Technology Data Exchange (ETDEWEB)

    Fajardo, O Y; Mazo, J J, E-mail: yovany@unizar.es [Departamento de Fisica de la Materia Condensada and Instituto de Ciencia de Materiales de Aragon, CSIC-Universidad de Zaragoza, 50009 Zaragoza (Spain)

    2011-09-07

    We present a theoretical study of the effect of surface defects on atomic friction in the stick-slip dynamical regime of a minimalistic model. We focus on how the presence of defects and temperature change the average properties of the system. We have identified two main mechanisms which modify the mean friction force of the system when defects are considered. As expected, defects change the potential profile locally and thus affect the friction force. But the presence of defects also changes the probability distribution function of the tip slip length and thus the mean friction force. We corroborated both effects for different values of temperature, external load, dragging velocity and damping. We also show a comparison of the effects of surface defects and surface disorder on the dynamics of the system. (paper)

  14. Geometric Defects in Quantum Hall States

    CERN Document Server

    Gromov, Andrey

    2016-01-01

    We describe a geometric (or gravitational) analogue of the Laughlin quasiholes in the fractional quantum Hall states. Analogously to the quasiholes these defects can be constructed by an insertion of an appropriate vertex operator into the conformal block representation of a trial wavefunction, however, unlike the quasiholes these defects are extrinsic and do not correspond to true excitations of the quantum fluid. We construct a wavefunction in the presence of such defects and explain how to assign an electric charge and a spin to each defect, and calculate the adiabatic, non-abelian statistics of the defects. The defects turn out to be equivalent to the genons in that their adiabatic exchange statistics can be described in terms of representations of the mapping class group of an appropriate higher genus Riemann surface. We present a general construction that, in principle, allows to calculate the statistics of $\\mathbb Z_n$ genons for any "parent" topological phase. We illustrate the construction on the ex...

  15. Induction of Th17 Lymphocytes and Treg Cells by Monocyte-Derived Dendritic Cells in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Science.gov (United States)

    Estrada-Capetillo, Lizbeth; Hernández-Castro, Berenice; Monsiváis-Urenda, Adriana; Alvarez-Quiroga, Crisol; Layseca-Espinosa, Esther; Abud-Mendoza, Carlos; Baranda, Lourdes; Urzainqui, Ana; Sánchez-Madrid, Francisco; González-Amaro, Roberto

    2013-01-01

    Dendritic cells (DCs) have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg) lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10) conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions. PMID:24288552

  16. Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases.

    Science.gov (United States)

    Rao, Nagarjun; Mackinnon, A Craig; Routes, John M

    2015-09-01

    Common variable immunodeficiency is a primary immunodeficiency of unknown etiology characterized by low serum immunoglobulin G, a decreased ability to make specific antibodies, and variable T-cell defects. Approximately 10-30% of patients with common variable immunodeficiency develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathologic findings termed granulomatous and lymphocytic interstitial lung disease. In this study, we characterized the histologic and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation, and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells was present, with a striking absence of FOXP3-positive T-regulatory cells. This heretofore unrecognized immunohistochemical finding needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis.

  17. Induction of Th17 Lymphocytes and Treg Cells by Monocyte-Derived Dendritic Cells in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Lizbeth Estrada-Capetillo

    2013-01-01

    Full Text Available Dendritic cells (DCs have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC’s (mo-DCs on the generation of Th17 and T regulatory (Treg lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA, twelve with systemic lupus erythematosus (SLE, and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10 conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC’s cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions.

  18. Cytotoxicity of lymphocytes from melanoma patients against autologous tumor cells and its potentiation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bykovskaya, S.N.; Iobadze, M.S.; Kupriyanova, T.A.; Demidov, L.V.

    1987-06-01

    The specific and natural cytotoxicity of peripheral blood lymphocytes from patients with melanomas was compared and stimulation with autologous tumor cells or a pool of allogeneic lymphocytes from five healthy blood donors also was used to potentiate the specific antitumor activity of the patients' lymphocytes. To assess cytolytic ability, cells of an autologous tumor, cells of the K-562 line, autologous peripheral blood lymphocytes, and blast cells obtained from these lymphocytes after stimulation by phytohemagglutinin were used as the target cells. The target cells were incubated in a medium containing sodium chromate and were labelled with the chromium 51 isotope.

  19. Welding defects at friction stir welding

    Directory of Open Access Journals (Sweden)

    P. Podržaj

    2015-04-01

    Full Text Available The paper presents an overview of different types of defects at friction stir welding. In order to explain the reasons for their occurrence a short theoretical background of the process is given first. The main emphasis is on the parameters that influence the process. An energy supply based division of defects into three disjoint groups was used. The occurring defects are demonstrated on various materials.

  20. Topological defects in two-dimensional crystals

    OpenAIRE

    Chen, Yong; Qi, Wei-Kai

    2008-01-01

    By using topological current theory, we study the inner topological structure of the topological defects in two-dimensional (2D) crystal. We find that there are two elementary point defects topological current in two-dimensional crystal, one for dislocations and the other for disclinations. The topological quantization and evolution of topological defects in two-dimensional crystals are discussed. Finally, We compare our theory with Brownian-dynamics simulations in 2D Yukawa systems.

  1. Defect Characterization Using Two-Dimensional Arrays

    Science.gov (United States)

    Velichko, A.; Wilcox, P. D.

    2011-06-01

    2D arrays are able to `view' a given defect from a range of angles leading to the possibility of obtaining richer characterization detail than possible with 1D arrays. In this paper a quantitative comparison of 2D arrays with different element layouts is performed. A technique for extracting the scattering matrix of a defect from the raw 2D array data is also presented. The method is tested on experimental data for characterization of various volumetric defects.

  2. Theory and Phenomenology of Spacetime Defects

    CERN Document Server

    Hossenfelder, Sabine

    2014-01-01

    Whether or not space-time is fundamentally discrete is of central importance for the development of the theory of quantum gravity. If the fundamental description of space-time is discrete, typically represented in terms of a graph or network, then the apparent smoothness of geometry on large scales should be imperfect -- it should have defects. Here, we review a model for space-time defects and summarize the constraints on the prevalence of these defects that can be derived from observation.

  3. Folding defect affine Toda field theories

    CERN Document Server

    Robertson, C

    2013-01-01

    A folding process is applied to fused a^(1)_r defects to construct defects for the non-simply laced affi?ne Toda ?field theories of c^(1)_n, d^(2)_n and a^(2)_n at the classical level. Support for the hypothesis that these defects are integrable in the folded theories is provided by the observation that transmitted solitons retain their form. Further support is given by the demonstration that energy and momentum are conserved.

  4. Phosphorous–vacancy–oxygen defects in silicon

    KAUST Repository

    Wang, Hao

    2013-07-30

    Electronic structure calculations employing the hybrid functional approach are used to gain fundamental insight in the interaction of phosphorous with oxygen interstitials and vacancies in silicon. It recently has been proposed, based on a binding energy analysis, that phosphorous–vacancy–oxygen defects may form. In the present study we investigate the stability of this defect as a function of the Fermi energy for the possible charge states. Spin polarization is found to be essential for the charge neutral defect.

  5. Diverse ability of maternal immune stimulation to reduce birth defects in mice exposed to teratogens: a review.

    Science.gov (United States)

    Hrubec, T C; Prater, M R; Mallela, M K; Gogal, R M; Guo, T L; Holladay, S D

    2012-06-01

    Stimulating the maternal immune system before or during pregnancy can dramatically improve morphologic outcome in mice that have been exposed to teratogens. For example, maternal immune stimulation in mice reduced craniofacial and palate defects, heart defects, digit and limb defects, tail malformations and neural tube defects caused by diverse teratogens that included chemical agents, hyperthermia, X-rays and diabetes mellitus. Several different procedures of immune stimulation were effective and included footpad injection with Freund's Complete Adjuvant, intraperitoneal (IP) injection with inert particles or attenuated Bacillus Calmette-Guerin, intrauterine injection with allogenic or xenogenic lymphocytes, or intravascular, intrauterine or IP injection with immunomodulatory cytokines. Limited information is available regarding mechanisms by which such immune stimulation reduces fetal dysmorphogenesis; however, cytokines of maternal origin have been suggested as effector molecules that act on the placenta or fetus to improve development. These collective data raise novel questions about the possibility of unrecognized maternal immune system regulatory activity in normal fetal development. This manuscript reviews the literature showing maternal immune protection against morphologic birth defects. Potential operating mechanisms are discussed, and the possibility is considered that a suppressed maternal immune system may negatively impact fetal development.

  6. Defect interactions within a group of subcascades

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    The evolution of the defect distributions within high energy cascades that contain multiple subcascades is studied as a function of temperature for cascades in copper. Low energy cascades generated with molecular dynamics are placed in close proximity to simulate the arrangement of subcascades within a high energy event, then the ALSOME code follows the evolution of the cascade damage during short term annealing. The intersubcascade defect interactions during the annealing stage are found to be minimal. However, no conclusions regarding effects of subcascades on defect production should be drawn until intersubcascade defect interactions during the quenching stage are examined.

  7. Antigravity from a spacetime defect

    CERN Document Server

    Klinkhamer, F R

    2013-01-01

    A nonsingular localized static classical solution is constructed for standard Einstein gravity coupled to an SO(3)\\times SO(3) chiral model of scalars [Skyrme model]. The construction proceeds in three steps. First, an Ansatz is presented for a solution with nontrivial topology of the spacetime manifold. Second, an exact vacuum solution of the reduced field equations is obtained. Third, matter fields are included and a numerical solution is found. This numerical solution has a negative effective mass, meaning that the gravitational force on a distant point mass is repulsive. The origin of the negative effective mass must lie in the surgery needed to create the "defect" from Minkowski spacetime, but this process involves topology change and lies outside the realm of classical Einstein gravity.

  8. Renyi entropy and conformal defects

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Lorenzo [Humboldt-Univ. Berlin (Germany). Inst. fuer Physik; Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Meineri, Marco [Scuola Normale Superiore, Pisa (Italy); Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Istituto Nazionale di Fisica Nucleare, Pisa (Italy); Myers, Robert C. [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Smolkin, Michael [California Univ., Berkely, CA (United States). Center for Theoretical Physics and Department of Physics

    2016-04-18

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  9. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.

    NARCIS (Netherlands)

    Desrosiers, T.A.; Herring, A.H.; Shapira, S.K.; Hooiveld, M.; Luben, T.J.; Herdt-Losavio, M.L.; Lin, S.; Olshan, A.F.

    2012-01-01

    Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation

  10. Repairing articular cartilage defects with tissue-engineering cartilage in rabbits

    Institute of Scientific and Technical Information of China (English)

    SONG Hong-xing; LI Fo-bao; SHEN Hui-liang; LIAO Wei-ming; LIU Miao; WANG Min; CAO Jun-ling

    2006-01-01

    Objective: To investigate the effect of cancellous bone matrix gelatin (BMG) engineered with allogeneic chondrocytes in repairing articular cartilage defects in rabbits.Methods: Chondrocytes were seeded onto three-dimensional cancellous BMG and cultured in vitro for 12 days to prepare BMG-chondrocyte complexes. Under anesthesia with 2.5% pentobarbital sodium (1 ml/kg body weight), articular cartilage defects were made on the right knee joints of 38 healthy New Zealand white rabbits (regardless of sex, aged 4-5 months and weighing 2.5-3 kg) and the defects were then treated with 2.5 % trypsin.Then BMG-chondrocyte complex (Group A, n=18 ),BMG ( Group B, n=10), and nothing ( Group C, n=10)were implanted into the cartilage defects, respectively. The repairing effects were assessed by macroscopic, histologic,transmission electron microscopic (TEM) observation,immunohistochemical examination and in situ hybridization detection, respectively, at 2, 4, 8, 12 and 24 weeks after operation.Results: Cancellous BMG was degraded within 8 weeks after operation. In Group A, lymphocyte infiltration was observed around the graft. At 24 weeks after operation, the cartilage defects were repaired by cartilage tissues and the articular cartilage and subchondral bone were soundly healed. Proteoglycan and type Ⅱ collagen were detected in the matrix of the repaired tissues by Safranin-O staining and immunohistochemical staining,respectively. In situ hybridization proved gene expression of type Ⅱ collagen in the cytoplasm of chondrocytes in the repaired tissues. TEM observation showed that chondrocytes and cartilage matrix in repaired tissues were almost same as those in the normal articular cartilage. In Group B, the defects were repaired by cartilage-fibrous tissues. In Group C, the defects were repaired only by fibrous tissues.Conclusions : Cancellous BMG can be regarded as the natural cell scaffolds for cartilage tissue engineering.Articular cartilage defects can be repaired by

  11. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study

    OpenAIRE

    Desrosiers, T.A.; Herring, A H; Shapira, S K; Hooiveld, M.; Luben, T.J.; Herdt-Losavio, M.L.; LIN, S.; Olshan, A.F.

    2012-01-01

    Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation and birth defects in a case–control study of cases comprising over 60 different types of birth defects (n=9998) and non-malformed controls (n=4066) with dates of delivery between 1997 and 2004. Me...

  12. Topological conformal defects with tensor networks

    Science.gov (United States)

    Hauru, Markus; Evenbly, Glen; Ho, Wen Wei; Gaiotto, Davide; Vidal, Guifre

    2016-09-01

    The critical two-dimensional classical Ising model on the square lattice has two topological conformal defects: the Z2 symmetry defect Dɛ and the Kramers-Wannier duality defect Dσ. These two defects implement antiperiodic boundary conditions and a more exotic form of twisted boundary conditions, respectively. On the torus, the partition function ZD of the critical Ising model in the presence of a topological conformal defect D is expressed in terms of the scaling dimensions Δα and conformal spins sα of a distinct set of primary fields (and their descendants, or conformal towers) of the Ising conformal field theory. This characteristic conformal data {Δα,sα}D can be extracted from the eigenvalue spectrum of a transfer matrix MD for the partition function ZD. In this paper, we investigate the use of tensor network techniques to both represent and coarse grain the partition functions ZDɛand ZD σ of the critical Ising model with either a symmetry defect Dɛ or a duality defect Dσ. We also explain how to coarse grain the corresponding transfer matrices MDɛand MD σ, from which we can extract accurate numerical estimates of {Δα,sα}Dɛ and {Δα,sα}Dσ. Two key ingredients of our approach are (i) coarse graining of the defect D , which applies to any (i.e., not just topological) conformal defect and yields a set of associated scaling dimensions Δα, and (ii) construction and coarse graining of a generalized translation operator using a local unitary transformation that moves the defect, which only exist for topological conformal defects and yields the corresponding conformal spins sα.

  13. Lymphocytic mural folliculitis and pancreatic carcinoma in a cat.

    Science.gov (United States)

    Lobetti, Remo

    2015-06-01

    A 9-year-old castrated domestic shorthair cat was presented with a 6 week history of progressive non-pruritic alopecia, polyphagia and weight loss. A diagnosis of lymphocytic mural folliculitis was made and the cat was treated with a combination of prednisolone and ciclosporin; this produced an improvement in the alopecia but no resolution. Sixteen months after the initial assessment and diagnosis, the cat was re-evaluated for intermittent vomiting and weight loss with normal appetite. On examination the dermatopathy was still evident and a mass involving the duodenum and pancreas was present, which was diagnosed as a pancreatic carcinoma. From this case it would appear that lymphocytic mural folliculitis might be an early dermatological manifestation of pancreatic neoplasia.

  14. Imaging the choreography of lymphocyte trafficking and the immune response.

    Science.gov (United States)

    Cahalan, Michael D; Parker, Ian

    2006-08-01

    The functioning of the immune system depends upon exquisitely choreographed interactions between its cellular constituents. Two-photon microscopy now enables us to visualize cell motility and cell-cell interactions deep within intact tissues and organs, both in explanted preparations and in vivo. Real-time immunoimaging techniques have illuminated the roles of random and chemokine-driven motility for cellular search strategies, the complex dynamics of cellular interactions, and the micro-anatomical localization and control of lymphocyte trafficking. Recently, advances have been made in these areas of research, as exemplified by studies investigating T cell-dendritic cell interactions, T cell-B cell interactions, and the regulation of lymphocyte egress from the lymph node.

  15. [239Pu and chromosomal aberrations in human peripheral blood lymphocytes].

    Science.gov (United States)

    Okladnikova, N D; Osovets, S V; Kudriavtseva, T I

    2009-01-01

    The genome status in somatic cells was assessed using the chromosomal aberration (CA) test in peripheral blood lymphocytes from 194 plutonium workers exposed to occupational radiation mainly from low-transportable compounds of airborne 230Pu. Pu body burden at the time of cytogenetic study varied from values close to the method sensitivity to values multiply exceeding the permissible level. Standard (routine) methods of peripheral blood lymphocytes cultivation were applied. Chromatid- and chromosomal-type structural changes were estimated. Aberrations were estimated per 100 examined metaphase cells. The quantitative relationship between the CA frequency and Pu body burden and the absorbed dose to the lung was found. Mathematical processing of results was carried out based on the phenomenological model. The results were shown as theoretical and experimental curves. The threshold of the CA yield was 0.43 +/- 0.03 kBq (Pu body burden) and 6.12 +/- 1.20 cGy (absorbed dose to the lung).

  16. Role of ofatumumab in treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Veliz M

    2011-05-01

    Full Text Available Marays Veliz, Javier Pinilla-IbarzH Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: The management of chronic lymphocytic leukemia (CLL has dramatically improved in the past decade with the addition of anti-CD20 monoclonal antibodies to the treatment armamentarium. Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved in the US and Europe for the treatment of CLL refractory to alemtuzumab and fludarabine. Preclinical data showed improved complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity compared with rituximab. Clinical studies have shown single-agent activity for ofatumumab in CLL and in other low-grade non-Hodgkin's lymphomas. Combination studies are being conducted to enhance the therapeutic efficacy of ofatumumab. This paper reviews some of the key clinical studies that led to approval of ofatumumab, and future directions.Keywords: ofatumumab, chronic lymphocytic leukemia, efficacy, safety

  17. Engineered lymphocytes to treat dinitrobenzene sulphonic acid colitis in mice.

    Science.gov (United States)

    Felley, Christian; Michetti, Pierre

    2003-12-01

    Current treatments of inflammatory bowel diseases are limited either by their lack of efficacy or their potential toxicity. In recent years, major advances have been obtained by the development of biological therapies. However, these types of treatment are systemic and can lead to serious adverse events. The new venue of local biological treatments would be most welcome. In this issue of the Journal, Castagliuolo et al. show that lymphocytes engineered to produce TGF-beta1 can reverse dinitrobenzene sulphonic acid-induced colitis in mice. These engineered lymphocytes selectively accumulate in the intestinal mucosa due to the homing properties of their alpha4beta7 integrins, a ligand for MAdCAM1. A local treatment restricted to the inflamed mucosa can thus be obtained. This opens a brand new area of research with the hope of restoring the immunoregulatory balance selectively in the inflamed tissues.

  18. Acute lymphocytic leukemia recurring in the spinal epidural space.

    Science.gov (United States)

    Higashida, Tetsuhiro; Kawasaki, Takashi; Sakata, Katsumi; Tanabe, Yutaka; Kanno, Hiroshi; Yamamoto, Isao

    2007-08-01

    A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL.

  19. Method and instrumentation for detection of rail defects, in particular rail top defects

    NARCIS (Netherlands)

    Li, Z.; Molodova, M.

    2011-01-01

    A method and instrumentation for detection of rail defects, in particular rail top defects, in a railway-track by measuring an axle box acceleration signal of a rail vehicle, wherein a longitudinal axle box acceleration signal is used as a measure to detect the occurrence of said rail defects, in pa

  20. Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Martin, C.; Romero, S.; Arriero, J.M.; Hernandez, L. [Hospital General Universitario, Servicios de Neumologia, Alicante (Spain); Sanchez-Paya, J. [Hospital General Universitario, Epidemiologia, Alicante (Spain); Massuti, B. [Hospital General Universitario, Oncologia, Alicante (Spain)

    1999-04-01

    The main aim of the present study was to assess the early diagnostic value of bronchoalveolar lavage (BAL) in radiation-induced lung injury in patients with breast carcinoma. Twenty-six females receiving postoperative radiotherapy for breast cancer were evaluated before and 0, 15, 30, 60 , and 180 days after radiotherapy. History, physical examination, chest radiographs, and pulmonary function tests were obtained. BAL, including lymphocyte subsets analysis, was limited to the second evaluation after radiotherapy. A group of 21 healthy females were used as control. Findings after radiotherapy in asymptomatic patients were compared with findings in a group of patients with radiation pneumonitis. Irradiated patients showed a significantly (p<0.01) greater percentage (29.5{+-}15.7%) of BAL lymphocytes than controls (6.2{+-}3.3%). No statistical differences existed in BAL findings between the irradiated and unirradiated sides of the chest. Percentages of BAL lymphocytes did not differ significantly between patients who developed subsequent pneumonitis (24.5{+-}13.5%) and those who did not develop pneumonitis (32.8{+-}16.5%). Patients with pneumonitis at the time of BAL had significantly higher (p<0.05) alveolar CD4 subset cells (24.8{+-}10.2%) than asymptomatic patients (15.2{+-}8.9%). Maximal reductions in total lung capacity (p<0.01), and residual volume (p<0.05) occurred 60 days after irradiation. The early lymphocytic alveolitis induced by unilateral thoracic radiotherapy in most patients with breast cancer is always bilateral and does not predict the subsequent development of radiological evidence of pneumonitis. (au) 38 refs.

  1. Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation.

    Science.gov (United States)

    Singh, Vineet Kumar; Dwivedi, Padmanabh; Chaudhary, B R; Singh, Ramesh

    2016-02-01

    Gymnemic acid is a mixture of triterpenoid saponins of oleanane class, isolated from Gymnema sylvestre Wild R.Br (family: Asclepidaceae), an herbal plant used in traditional medicine to treat diabetes. Effect of gymnemic acid (0.1-20 µg/mL) on in vitro mitogen (concanavalin A and lipopolysaccharide)-induced splenic lymphocyte proliferation was studied using rat as model. Significant (p sylvestre is scientifically supplemented with its immunomodulatory properties.

  2. Obinutuzumab treatment in the elderly patient with chronic lymphocytic leukemia

    OpenAIRE

    Seiter K; Mamorska-Dyga A

    2015-01-01

    Karen Seiter, Aleksandra Mamorska-DygaDepartment of Medicine, Division of Hematology/Oncology, New York Medical College, Valhalla, NY, USA Abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Fludarabine-based regimens demonstrate higher response rates in younger patients but have a significant risk of infection and are thus poorly tolerated by older, frail patients. Anti-CD20 monoclonal antibodies have added to the efficacy of chemotherapy ...

  3. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis.

    Science.gov (United States)

    Wang, Chenggong; Liao, Qiande; Hu, Yihe; Zhong, DA

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis.

  4. [Computer-assisted histocompatibility assessment in mixed lymphocyte culture (MLC)].

    Science.gov (United States)

    Schwartz, D; Hajek-Rosenmayr, A

    1987-02-20

    Analysis of the results of mixed lymphocyte culture (MLC) for compatibility testing preceding transplantation of bone marrow and other organs has so far required a vast input, both in terms of laboratory staff and work hours. We have developed a computer programme which performs this work rapidly. Graphics of the reaction patterns can be obtained, moreover, and these can prove a helpful tool in interpretation of the results.

  5. A study of peripheral T-Lymphocytes in alopecia areata

    Directory of Open Access Journals (Sweden)

    Sharma R

    1995-01-01

    Full Text Available Estimation of peripheral T-lymphocytes (active and total was carried out in 100 cases of alopecia areata as per method described by Boyam (1977 and West et al (1978. Clinically patients were divided in two groups, alopecia areata circumscribed (group I and severe alopecia areata (group II. Thirty healthy subjects served as controls. Decrease in percentage of both active and total E-RFC was observed in 70% cases. The decrease was more significant in group II.

  6. Intramembrane particles and the organization of lymphocyte membrane proteins.

    Science.gov (United States)

    Kuby, J M; Wofsy, L

    1981-03-01

    An experimental system was developed in which the majority of all lymphocyte cell-surface proteins, regardless of antigenic specificity, could be cross-linked and redistributed in the membrane to determine whether this would induce a corresponding redistribution of intramembrane particles (IMP). Mouse spleen cells were treated with P-diazoniumphenyl- beta-D-lactoside (lac) to modify all exposed cell-surface proteins. Extensive azo- coupling was achieved without significantly reducing cell viability or compromising cellular function in mitogen- or antigen-stimulated cultures. When the lac-modified cell- surface proteins were capped with a sandwich of rabbit antilactoside antibody and fluorescein-goat anti-rabbit Ig, freeze-fracture preparations obtained from these cells revealed no obvious redistribution of IMP on the majority of fracture faces. However, detailed analysis showed a statistically significant 35 percent decrease (P less than 0.01) in average IMP density in the E face of the lac-capped spleen cells compared with control cells, whereas a few E-face micrographs showed intense IMP aggregation. In contrast, there was no significant alteration of P-face IMP densities or distribution. Apparently, the majority of E-face IMP and virtually all P-face IMP densities or distribution. Apparently, the majority of E-face IMP and virtually all P-face IMP do not present accessible antigenic sites on the lymphocyte surface and do not associate in a stable manner with surface protein antigens. This finding suggests that IMP, as observed in freeze-fracture analysis, may not comprise a representative reflection of lymphocyte transmembrane protein molecules and complexes because other evidence establishes: (a) that at least some common lymphocyte surface antigens are indeed exposed portions of transmembrane proteins and (b) that the aggregation of molecules of any surface antigen results in altered organization of contractile proteins at the cytoplasmic face of the membrane.

  7. Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis

    Science.gov (United States)

    2011-01-31

    common finding in many other hemorrhagic fever viruses, in- cluding Lassa , Marburg, Crimean Congo hemorrhagic fever , and some Hantavirus infections... fever , resulting in death in up to 90% of infected humans. EBOVinfection induces massive bystander lymphocyte apoptosis; however, neither the cellular...Jonathan E. McDunn,‡ Richard S. Hotchkiss,‡ and Sina Bavari* Ebolavirus (EBOV) is a member of the filovirus family and causes severe hemorrhagic fever

  8. In vitro genotoxicity of pyridine in human lymphocytes.

    Science.gov (United States)

    Emelnsia, Aida D; Rather, Irfan A

    2016-05-01

    This work was carried out to study the genotoxicity of pyridine in vitro on human leucocyte culture. Cyclophosphamide, a well-known carcinogen was used as positive control. The four different concentrations of pyridine and cyclophosphamide showed breaks and pulverization of chromosomes in dose dependent manner. Higher number of pulverization was observed with higher concentration of pyridine (3.25μg/mL). Based on this data, our results confirm that both pyridine and its precursor showed genotoxicity against human lymphocytes.

  9. Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

    Centers for Disease Control (CDC) Podcasts

    2007-05-16

    Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.  Created: 5/16/2007 by CDC, Office of the Director.   Date Released: 5/16/2007.

  10. The cytotoxic T lymphocyte immune synapse at a glance.

    Science.gov (United States)

    Dieckmann, Nele M G; Frazer, Gordon L; Asano, Yukako; Stinchcombe, Jane C; Griffiths, Gillian M

    2016-08-01

    The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers.

  11. Elevated Neutrophil Lymphocyte Ratio in Recurrent Optic Neuritis

    Directory of Open Access Journals (Sweden)

    Hande Guclu

    2015-01-01

    Full Text Available Purpose. To demonstrate the relation between optic neuritis (ON and systemic inflammation markers as neutrophil lymphocyte ratio (N/L ratio, platelet count, mean platelet volume (MPV, and red cell distribution width (RDW and furthermore to evaluate the utilization of these markers to predict the frequency of the ON episodes. Methods. Forty-two patients with acute ON and forty healthy subjects were enrolled into the study. The medical records were reviewed for age, sex, hemoglobin (Hb, Haematocrit (Htc, RDW, platelet count, MPV, white blood cell count (WBC, neutrophil and lymphocyte count, and neutrophil lymphocyte ratio (N/L ratio. Results. The mean N/L ratio, platelet counts, and RDW were significantly higher in ON group (p=0.000, p=0.048, and p=0.002. There was a significant relation between N/L ratio and number of episodes (r=0.492, p=0.001. There was a statistically significant difference for MPV between one episode group and recurrent ON group (p=0.035. Conclusions. Simple and inexpensive laboratory methods could help us show systemic inflammation and monitor ON patients. Higher N/L ratio can be a useful marker for predicting recurrent attacks.

  12. Atopic dermatitis: serum immunoglobulins and T-lymphocyte subpopulations.

    Science.gov (United States)

    Valdés Sánchez, A F; Gómez Echevarría, A H; Lastra Alfonso, G

    1991-04-01

    A group of patients with atopic dermatitis who attended the Allergy Outpatient Service of the Hermanos Ameijeiras Clinical Surgical Hospital from May, 1987 to May, 1988 were studied. The patients were assigned to 2 groups; the first one composed of 38 patients and the second one composed of 12 non-allergic, supposedly healthy subjects. Different tests were carried out for the quantification of total serum immunoglobulins (A, G, M, E) by means of the radial immunodiffusion method and the ELISA ultramicromethod. They were also submitted to quantification of lymphocyte subpopulations by means of the indirect immunofluorescence test with monoclonal antibodies, using Cuban antiserum prepared at the National Institute of Oncology and Radiobiology. In our study IgG and IgA values were within normal limits in patients, contrary to the statistically significant increase in IgM and IgE values. The relative values of total T-lymphocytes (anti-T3) and of the suppressor lymphocyte subpopulations decreased.

  13. Apicobasal Polarity Controls Lymphocyte Adhesion to Hepatic Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Natalia Reglero-Real

    2014-09-01

    Full Text Available Loss of apicobasal polarity is a hallmark of epithelial pathologies. Leukocyte infiltration and crosstalk with dysfunctional epithelial barriers are crucial for the inflammatory response. Here, we show that apicobasal architecture regulates the adhesion between hepatic epithelial cells and lymphocytes. Polarized hepatocytes and epithelium from bile ducts segregate the intercellular adhesion molecule 1 (ICAM-1 adhesion receptor onto their apical, microvilli-rich membranes, which are less accessible by circulating immune cells. Upon cell depolarization, hepatic ICAM-1 becomes exposed and increases lymphocyte binding. Polarized hepatic cells prevent ICAM-1 exposure to lymphocytes by redirecting basolateral ICAM-1 to apical domains. Loss of ICAM-1 polarity occurs in human inflammatory liver diseases and can be induced by the inflammatory cytokine tumor necrosis factor alpha (TNF-α. We propose that adhesion receptor polarization is a parenchymal immune checkpoint that allows functional epithelium to hamper leukocyte binding. This contributes to the haptotactic guidance of leukocytes toward neighboring damaged or chronically inflamed epithelial cells that expose their adhesion machinery.

  14. The Use of Isolated Human Lymphocytes in Mycotoxin Cytotoxicity Testing

    Directory of Open Access Journals (Sweden)

    Mike F. Dutton

    2008-08-01

    Full Text Available The cytotoxicity of selected mycotoxins against isolated human lymphocytes was investigated, as a means of detecting mycotoxins in extracts derived from cereal samples. The methodology was based on the ability of viable cells to reduce methyl tetrazolium bromide to a purple formazan dye that could be quantitated by spectrophometric means and hence give a measure of the cytotoxicity of added substances. The results showed that there was good correlation with the occurrence of identified mycotoxins with only a minimum of false positives. For example, of the 13 samples of barley or barley derivatives that were positive for the mycotoxins, fumonisin B1 (FB1 deoxynivalenol (DON and ochratoxin A (OTA, all gave positive cytotoxicity responses. Two samples negative for mycotoxins gave no cytotoxicity responses. There was little variation between the results for lymphocytes drawn from the same healthy volunteer on three different occasions. Furthermore, for two of the mycotoxins tested (FB1 and DON it was possible to correlate general levels of mycotoxins present to the cytotoxic response of the lymphocytes but not for OTA, where it was concluded that interfering substances prevented direct correlation. It was concluded that this method was suited for general application as it could handle relatively high number of samples in a short period of time.

  15. Chromosomal instability in the lymphocytes of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harsimran Kaur

    2009-01-01

    Full Text Available Genomic instability in the tumor tissue has been correlated with tumor progression. In the present study, chromosomal aberrations (CAs in peripheral blood lymphocytes (PBLs of breast tumor patients were studied to assess whether chromosomal instability (CIN in PBLs correlates with aggressiveness of breast tumor (i.e., disease stage and has any prognostic utility. Cultured blood lymphocyte metaphases were scored for aberrations in 31 breast cancer patients and 20 healthy age and sex-matched controls. A variety of CAs, including aneuploidy, polyploidy, terminal deletions, acentric fragments, double minutes, chromatid separations, ring chromosome, marker chromosome, chromatid gaps, and breaks were seen in PBLs of the patients. The CAs in patients were higher than in controls. A comparison of the frequency of metaphases with aberrations by grouping the patients according to the stage of advancement of disease did not reveal any consistent pattern of variation in lymphocytic CIN. Neither was any specific chromosomal abnormality found to be associated with the stage of cancer. This might be indicative of the fact that cancer patients have constitutional CIN, which predisposes them to the disease, and this inherent difference in the level of genomic instability might play a role in disease progression and response to treatment.

  16. Preparation of Internal Quality Control Material for Lymphocyte Subset Analysis.

    Science.gov (United States)

    Roh, Eun Youn; Shin, Sue; Yoon, Jong Hyun; Oh, Sohee; Park, Kyoung Un; Lee, Nuri; Song, Eun Young

    2016-07-01

    Lymphocyte subset analysis is widely used in clinical laboratories, and more than two levels of daily QC materials are required for reliable results. Commercially available, expensive QC materials have short shelf lives and may not be suitable in resource-poor settings. We compared different methods for preparing homemade QC material, including fixation with 1%, 2%, or 4% paraformaldehyde (PFA); freezing with 10% dimethylsulfoxide (DMSO), 0.1% bovine serum albumin-phosphate buffered saline, or after ethanolic dehydration; and using cryopreservation temperatures of -20°C, -80°C, or -196°C. We found an optimal experimental condition, which is 'fixation with 4% PFA, freezing with 10% DMSO, and storage at 80°C'. To evaluate long-term stability of QC materials prepared in this optimal condition, two levels of QC materials (QM1 and QM2) were thawed after 30, 33, 35, 37, 60, 62, 64, and 67 days of cryopreservation. Lymphocyte subset was analyzed with BD Multitest IMK kit (BD Biosciences, USA). QM1 and QM2 were stable after 1-2 months of cryopreservation (CV materials for lymphocyte subset analysis in resource-poor settings.

  17. Electrostimulation of rat callus cells and human lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aro, H.; Eerola, E.; Aho, A.J.; Penttinen, R.

    1984-01-01

    Asymmetrical pulsing low voltage current was supplied via electrodes to cultured rat fracture callus cells and human peripheral blood lymphocytes. The (/sup 3/H)thymidine incorporation of the callus cells and 5-(/sup 125/I)iodo-2'-deoxyuridine incorporation of the lymphocytes were determined. The growth pattern of callus cells (estimated by cellular density) did not respond to electrical stimulation. However, the uptake of (/sup 3/H)thymidine was increased at the early phase of cell proliferation and inhibited at later phases of proliferation. The (/sup 3/H)thymidine uptake of confluent callus cell cultures did not respond to electrical stimulation. Lymphocytes reacted in a similar way; stimulated cells took up more DNA precursor than control cells at the early phase of stimulation. During cell division, induced by the mitogens phytohemagglutinin and Concanavalin-A, the uptake of DNA precursor by stimulated cells was constantly inhibited. The results suggest that electrical stimuli affect the uptake mechanisms of cell membranes. The duality of the effect seems to be dependent on the cell cycle.

  18. Interference of CD95 expression on human lymphocytes.

    Science.gov (United States)

    Petanova, Jitka; Fucikova, Terezie; Bencko, Vladimir

    2002-02-01

    The study presents the exogenous influence of cadmium in comparison with zinc on the apoptosis of human lymphocytes by CD95 expression and its kinetic changes. The salts of both metals were used in final concentrations of 20 microM in cell cultures with whole blood. The duration of cultivation was 18 and 90 hours. The expression of surface antigens was evaluated by flow cytometry with monoclonal antibodies. In cultures of not stimulated cells we found in average 51.54% CD95 positive lymphocytes. The kinetic study of untreated cells showed elevation after 18 hours of cultivation and a very low expression after 90 hours. The CD95 expression on lymphocytes in cell culture with cadmium and zinc was lower after 18 hours of cultivation than in untreated cells. After 90 hours cultivation we found low levels of CD95 expression on cells treated with cadmium and a great individual variability in the number of positive cells upon the influence of zinc.

  19. [Retarded excision of pyrimidine dimers in human unstimulated lymphocytes].

    Science.gov (United States)

    Snopov, S A; Roza, L; de Gruijl, F R

    2006-01-01

    Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of peripheral lymphocytes after their UVC-irradiation and cultivation, we have found that within the first four hours of cultivation the CPD-specific fluorescent signal from cell nuclei increased. Earlier, a similar increase in binding of antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured DNA isolated from UV-irradiated Chinese hamster ovary cells was reported (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair enzyme might induce such of DNA modification in lymphocyte nuclei that increased specific antibody binding to DNA fragments with lesions. We suggest that enzymatic formation of open structures in DNA predominated qualitatively over dual-incision and excision of these fragments, and resulted in the enhanced exposure of the pyrimidine dimers in nuclei to specific antibodies. The results evidence that nucleotid excision repair in unstimualted human lymphocytes being deficient in dual incision and removal of UV-induced DNA lesions appear to be capable of performing chromatin relaxation and pre-incision uncoiling of DNA fragments with lesions.

  20. Control of T lymphocyte morphology by the GTPase Rho

    Directory of Open Access Journals (Sweden)

    Caudell Eva G

    2003-02-01

    Full Text Available Abstract Background Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. Results Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin β1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to β1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. Conclusions GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility.

  1. A case of chronic lymphocytic leukemia with massive ascites

    Directory of Open Access Journals (Sweden)

    Meliha Nalcaci

    2012-10-01

    Full Text Available An 81-year old woman with a history of chronic lymphocytic leukemia (CLL was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC count 28.5x109/L and platelets 38.4x109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely gran- ular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites.

  2. 7 CFR 52.780 - Defects.

    Science.gov (United States)

    2010-01-01

    ... PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1... cherry. (b) (A) classification. Canned red tart pitted cherries that are practically free from defects...) (B) classification. Canned red tart pitted cherries that are reasonably free from defects may...

  3. Positron analysis of defects in metals

    NARCIS (Netherlands)

    van Veen, A; Kruseman, AC; Schut, H; Mijnarends, PE; Kooi, BJ; De Hosson, JTM; Jean, YC; Eldrup, M; Schrader, DM; West, RN

    1997-01-01

    New methods are discussed to improve defect analysis. The first method employs mapping of two shape parameters, S and W, of the positron annihilation photopeak. It is demonstrated that the combined use of S and W allows to a better discrimination of defects. The other method is based on background s

  4. Orbital dystopia due to orbital roof defect.

    Science.gov (United States)

    Rha, Eun Young; Joo, Hong Sil; Byeon, Jun Hee

    2013-01-01

    We performed a retrospective review of patients who presented with delayed dystopia as a consequence of an orbital roof defect due to fractures and nontraumatic causes to search for a correlation between orbital roof defect size and surgical indications for the treatment thereof. Retrospective analyses were performed in 7 patients, all of whom presented with delayed dystopia due to orbital roof defects, between January 2001 and June 2011. The causes of orbital roof defects were displaced orbital roof fractures (5 cases), tumor (1 case), and congenital sphenoid dysplasia (1 case). All 7 patients had initially been treated conservatively and later presented with significant dystopia. The sizes of the defects were calculated on computed tomographic scans. Among the 7 patients, aspiration of cerebrospinal fluid, which caused ocular symptoms, in 1 patient with minimal displaced orbital roof and reconstruction with calvarial bone, titanium micromesh, or Medpor in 6 other patients were performed. The minimal size of the orbital roof in patients who underwent orbital roof reconstruction was 1.2 cm (defect height) x 1.0 cm (defect length), 0.94 cm(2). For all patients with orbital dystopia, displacement of the globe was corrected without any complications, regardless of whether the patient was evaluated grossly or by radiology. In this retrospective study, continuous monitoring of clinical signs and active surgical management should be considered for cases in which an orbital roof defect is detected, even if no definite symptoms are noted, to prevent delayed sequelae.

  5. Birth defects in children with newborn encephalopathy

    NARCIS (Netherlands)

    Felix, JF; Badawi, N; Kurinczuk, JJ; Bower, C; Keogh, JM; Pemberton, PJ

    2000-01-01

    This study was designed to investigate birth defects found in association with newborn encephalopathy. All possible birth defects were ascertained in a population-based study of 276 term infants with moderate or severe encephalopathy and 564 unmatched term control infants. A strong association betwe

  6. Simple intrinsic defects in InAs :

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2013-03-01

    This Report presents numerical tables summarizing properties of intrinsic defects in indium arsenide, InAs, as computed by density functional theory using semi-local density functionals, intended for use as reference tables for a defect physics package in device models.

  7. On varieties with higher osculating defect

    CERN Document Server

    De Poi, Pietro; Ilardi, Giovanna

    2012-01-01

    In this paper, using the method of moving frames, we generalise some of Terracini's results on varieties with tangent defect. In particular, we characterise varieties with higher order osculating defect in terms of Jacobians of higher fundamental forms and moreover we characterise varieties with "small" higher fundamental forms as contained in scrolls.

  8. Line defects and (framed) BPS quivers

    CERN Document Server

    Cirafici, Michele

    2013-01-01

    The BPS spectrum of certain N=2 supersymmetric field theories can be determined algebraically by studying the representation theory of BPS quivers. We introduce methods based on BPS quivers to study line defects. The presence of a line defect opens up a new BPS sector: framed BPS states can be bound to the defect. The defect can be geometrically described in terms of laminations on a curve. To a lamination we associate certain elements of the Leavitt path algebra of the BPS quiver and use them to compute the framed BPS spectrum. We also provide an alternative characterization of line defects by introducing framed BPS quivers. Using the theory of (quantum) cluster algebras, we derive an algorithm to compute the framed BPS spectra of new defects from known ones. Line defects are generated from a framed BPS quiver by applying certain sequences of mutation operations. Framed BPS quivers also behave nicely under a set of "cut and join" rules, which can be used to study how N=2 systems with defects couple to produc...

  9. Microphthalmia with linear skin defects syndrome.

    Science.gov (United States)

    García-Rabasco, Ana; De-Unamuno, Blanca; Martínez, Francisco; Febrer-Bosch, Isabel; Alegre-de-Miquel, Víctor

    2013-01-01

    Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X-linked-dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X-chromosome inactivation pattern (85:15) was observed.

  10. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    D.L. Zanette

    2007-11-01

    Full Text Available MicroRNAs (miRNAs are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their association with cancer. We determined the miRNA expression profile of chronic and acute lymphocytic leukemias (CLL and ALL using the TaqMan® MicroRNA Assays Human Panel (Applied Biosystems. Pooled leukemia samples were compared to pooled CD19+ samples from healthy individuals (calibrator by the 2-DDCt method. Total RNA input was normalized based on the Ct values obtained for hsa-miR-30b. The five most highly expressed miRNAs were miR-128b, miR-204, miR-218, miR-331, and miR-181b-1 in ALL, and miR-331, miR-29a, miR-195, miR-34a, and miR-29c in CLL. To our knowledge, this is the first report associating miR-128b, miR-204 and miR-331 to hematological malignancies. The miR-17-92 cluster was also found to be up-regulated in ALL, as previously reported for some types of lymphomas. The differences observed in gene expression levels were validated for miR-331 and miR-128b in ALL and CD19+ samples. These miRNAs were up-regulated in ALL, in agreement with our initial results. A brief target analysis was performed for miR-331. One of its putative targets, SOCS1, promotes STAT activation, which is a known mediator of cell proliferation and survival, suggesting the possibility of an association between miR-331 and these processes. This initial screening provided information on miRNA differentially expressed in normal and malignant B-cells that could suggest the potential roles of these miRNAs in hematopoiesis and leukemogenesis.

  11. A collagen defect in homocystinuria.

    Science.gov (United States)

    Kang, A H; Trelstad, R L

    1973-10-01

    the two patients examined, reflecting a functional defect in collagen cross-linking. Although the concentration of homocysteine used in this study to demonstrate these effects in vitro is clearly higher than that which is observed in homocystinuric's plasma, the data do suggest a possible pathogenetic mechanism of connective tissue defect in homocystinuria.

  12. Online isolation of defects in cellular nanocomputers

    Institute of Scientific and Technical Information of China (English)

    Teijiro Isokawa; Shin'ya Kowada; Ferdinand Peper; Naotake Kamiura; Nobuyuki Matsui

    2007-01-01

    Unreliability will be a major issue for computers built from components at nanometer scales.Thus,it's to be expected that such computers will need a high degree of defect-tolerance to overcome components' defects which have arisen during the process of manufacturing.This paper presents a novel approach to defect-tolerance that is especially geared towards nanocomputers based on asynchronous cellular automata.According to this approach,defective cells are detected and isolated by small configurations that move around randomly in cellular space.These configurations,called random flies,will attach to configurations that are static,which is typical for configurations that contain defective cells.On the other hand,dynamic configurations,like those that conduct computations,will not be isolated from the rest of the cellular space by the random flies,and will be able to continue their operations unaffectedly.

  13. Defect and functionalized graphene for supercapacitor electrodes

    Science.gov (United States)

    Taluja, Yogita; SanthiBhushan, Boddepalli; Yadav, Shekhar; Srivastava, Anurag

    2016-10-01

    The structural, electronic and transport properties of defected (single vacancy and double vacancy) and nitrogen functionalized graphene sheets have been analysed within the framework of Density Functional Theory (DFT) and non-equilibrium Green's function (NEGF) formalism for their possible application as supercapacitor electrodes. Formation energy calculations reveal the increasing stability of defect with nitrogen functional doping concentration at its edges. The extracted electronic properties reveal the presence of acceptor-type energy levels at Fermi level in the defected and functionalized sheets. Transport studies portray remarkable increase in electrical conductivity of graphene sheet after the formation of single vacancy defect and its functionalization. Especially, the Single Vacancy Trimerized pyridine-type defect (SVT) configuration has demonstrated superior thermodynamic stability as well as electrical conductance in comparison to all the other configurations.

  14. Defect-Tolerant Monolayer Transition Metal Dichalcogenides

    DEFF Research Database (Denmark)

    Pandey, Mohnish; Rasmussen, Filip Anselm; Kuhar, Korina;

    2016-01-01

    -principles investigation of defect tolerance in 29 monolayer transition metal dichalcogenides (TMDs) of interest for nanoscale optoelectronics. We find that the TMDs based on group VI and X metals form deep gap states upon creation of a chalcogen (S, Se, Te) vacancy, while the TMDs based on group IV metals form only...... shallow defect levels and are thus predicted to be defect-tolerant. Interestingly, all the defect sensitive TMDs have valence and conduction bands with a very similar orbital composition. This indicates a bonding/antibonding nature of the gap, which in turn suggests that dangling bonds will fall inside...... the gap. These ideas are made quantitative by introducing a descriptor that measures the degree of similarity of the conduction and valence band manifolds. Finally, the study is generalized to nonpolar nanoribbons of the TMDs where we find that only the defect sensitive materials form edge states within...

  15. The Doppler peaks from a generic defect

    CERN Document Server

    Magueijo, J

    1996-01-01

    We investigate which of the exotic Doppler peak features found for textures and cosmic strings are generic novelties pertaining to defects. We find that the ``out of phase'' texture signature is an accident. Generic defects, when they generate a secondary peak structure similar to inflation, apply to it an additive shift. It is not necessary for this shift to be ``out of phase''. We also show which factors are responsible for the absence of secondary oscillations found for cosmic strings. Within this general analysis we finally consider the conditions under which topological defects and inflation can be confused. It is argued that only \\Omega=1 inflation and a defect with a horizon size coherence length have a chance to be confused. Any other inflationary or defect model always differ distinctly. (To appear in the proceedings of the XXXIth Moriond meeting, ``Microwave Background Anisotropies'')

  16. Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-06

    Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  17. The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Platz, P;

    1985-01-01

    Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50...

  18. The role of point defects and defect complexes in silicon device processing. Summary report and papers

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B.; Tan, T.Y.

    1994-08-01

    This report is the summary of the third workshop on the role of point defects and defect complexes in silicon device processing. The workshop was organized: (1) to discuss recent progress in the material quality produced by photovoltaic Si manufacturers, (2) to foster the understanding of point defect issues in Si device processing, (3) to review the effects of inhomogeneities on large- area solar cell performance, (4) to discuss how to improve Si solar cell processing, and (5) to develop a new understanding of gettering, defect passivation, and defect annihilation. Separate abstract were prepared for the individual papers, for the database.

  19. Activation of secretion and surface alteration of cytolytic T-lymphocytes interacting with target cells.

    Science.gov (United States)

    Bykovskaya, S N; Shevelev, A A; Kupriyanova, T A

    1988-01-01

    Cells obtained in mixed lymphocyte culture (MLC) and memory cells adsorbed on the surface of target cells (TC) were examined using scanning and transmission electron microscopy depending on the time of interaction with TC. Three types of lymphocytes were revealed: type I - cells of spherical shape with a smooth surface or an insignificant amount of microvilli; predominantly small and medium-sized lymphocytes contacting TC with non significant involvement of their surface or by several microvilli; type II - oval or round-shaped lymphocytes evenly covered with microvilli with considerably enlarged region of contact; type III cells - predominantly large lymphocytes and lymphoblasts flattened (spread) on TC, with multiple microvilli, ridge-like projections, and ruffles on their surface. TEM revealed activation of the secretory apparatus in the cytoplasm of such lymphocytes. With increased time of interaction, type III cells increase in number (from 8.6% after 10 min to 90.2% after 60 min of incubation). Memory cells show no morphologic signs of secretion in correlation with the absence of lysis of TC on which they are adsorbed. The surface of the lymphocytes adsorbed on the substrate with poly-L-lysin is not noticeably altered. It is suggested that 3 morphological types of lymphocytes correspond to 3 stages of secretion activation. Lymphocyte contact with TC surface is evidently a specific stimulus for activating secretory apparatus of CTL. SEM can be used for quantitation of activated lymphocytes.

  20. Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

    Science.gov (United States)

    McGillis, J P; Park, A; Rubin-Fletter, P; Turck, C; Dallman, M F; Payan, D G

    1989-07-01

    The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.