Sample records for cell-extrinsic defective lymphocyte

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

    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. Early activation defects in T lymphocytes from aged mice.

    Miller, R A; Garcia, G; Kirk, C J; Witkowski, J M


    Aging affects both calcium signals and protein kinase cascades in mouse T lymphocytes. The decline in calcium signal development largely represents differences between naive and memory T cells; the latter are resistant to increases in calcium concentration, and are more common in aged mice. Aging leads to declines in phosphorylation of a wide range of substrates in T cells stimulated by either anti-CD3 antibodies or by substances, such as phorbol myristate acetate (PMA) or ionomycin, that act at intracellular sites, but some phosphoproteins respond only in old T cells, and others respond regardless of age. Tyrosine phosphorylation of the CD3 zeta chain declines with age, both in resting T cells and after activation, but the proportion of Zap-70 that is bound to CD3 zeta increases in T cells from old mice. Zap-70 function and phosphorylation of CD3 zeta-associated Zap-70 change only slightly after stimulation of T cells by anti-CD3 and anti-CD4, and are at similar levels in activated old and young T cells. Nonetheless, induction of Raf-1, MEK, and ERK kinase activity declines with age in CD4 T cells. The effect of aging on T-cell activation is not simply an overall decline in signal intensity, but a set of qualitative changes that differ among subsets and depend at least partly on the nature of the stimulus. PMID:9476667

  3. Low sodium diet corrects the defect in lymphocyte beta-adrenergic responsiveness in hypertensive subjects.

    Feldman, R D; Lawton, W J; McArdle, W L


    To determine the role of dietary sodium intake in the reduction in beta-adrenergic sensitivity in hypertension, lymphocyte beta-receptors from 8 borderline hypertensive and 16 normotensive subjects were studied after 5 d on a high sodium diet (400 meq/d) and also following a low sodium diet (10 meq/d). During the high sodium diet, lymphocyte beta-receptor-stimulated adenylate cyclase activity, expressed as the relative increase over basal levels stimulated by the beta-agonist isoproterenol, w...

  4. Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated with defective activation of Ras

    Porcu, Pierluigi; Gaddy, Jay; Broxmeyer, Hal E.


    Human umbilical cord blood T lymphocytes (CBTL) respond to primary allostimulation but they do not proliferate upon rechallenge with alloantigen. Using PKH-26-labeled cells created a proliferative block that was observed only in CBTL that have divided during primary stimulation (PKH-26dim) but not in unstimulated (PKH-26bright) CBTL. CBTL’s secondary unresponsiveness resembles anergy and can be overcome by treatment with phorbol myristate acetate (PMA) and ionomycin or by high doses (50–100 u...

  5. Thymectomized, irradiated, and bone marrow-reconstituted chimeras have normal cytolytic T lymphocyte precursors but a defect in lymphokine production

    A model system has been developed to study extrathymic T cell differentiation; mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1+ cells. After 8 wk, the spleen cells of these athymic, bone marrow-reconstituted chimeras contain Thy-1+ precytolytic T lymphocytes (CTL) that are able to respond to antigen only if supernatant from Con A-activated T cells is added to culture. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be immature T cells. Initial evaluation of the CTL repertoire of these athymic mice demonstrated that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2-restricted, and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal mice but not in nude mice. In this report, the authors demonstrate a helper T cell defect in these thymectomized chimeras. These chimeras lack an Ly-1+ helper cell required for thymocytes to differentiate to CTL. Further studies revealed that when spleen cells from these thymectomized chimeras were stimulated with Con A, they produced normal levels of interleukin 2. However, these splenocytes were defective in the production of another factor needed for CTL differentiation

  6. Defective expression and function of the leukocyte associated Ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients.

    Barbara M Colombo

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig-like receptor (LAIR1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD, 20 systemic sclerosis (SSc patients, 14 rheumatoid arthritis (RA and 40 sex and age matched healthy donors (HD have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20(+ B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.

  7. 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

    Ko-Jen Li


    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.

  8. Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people

    The frequency of mutant T lymphocytes defective in T-cell receptor gene (α or β) expression was measured using the two-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of ≥ 1.5 Gy) and 125 of whom were distally exposed (DS86 doses of 228Th formerly used for radiodiagnosis. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for the measurement of recent exposures to genotoxic agents. (author)

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

    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

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

    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.

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

    Caimi Luigi


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

  12. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Jeroen Pouwels


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

  13. Lymphocyte Functions in Microgravity

    Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)


    To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

  14. Lymphocyte radiosensitivity in multiple sclerosis patients

    The purpose of the study was to characterize the radiosensitivity of the peripheral blood lymphocytes from Secondary Progressive Multiple Sclerosis (MS) patients in order to get insights in the ability of these cells to deal with DNA damage. Genetic defects in the repair mechanisms of DNA have not been systematically observed in MS but they have been found in other autoimmune diseases such as lupus erythematosus and rheumatoid arthritis, as well as in several disorders of the nervous system. Up to now investigations into cellular radio-sensitivity in MS patients comparative to healthy controls have yielded contradictory results. The following methods were used: The chromosomal radiosensitivity of lymphocytes was assessed after in vitro 2 Gy gamma irradiation in G0 phase of the cell cycle, using the micronucleus (MN) assay. The MN assay was performed on whole blood cultures, separated PBMC cultures, and CD4+ and CD8+ subsets of T lymphocytes from blood samples of the MS (n=26) patients and on concurrent samples of healthy individuals (n=22). The results obtained are summarized as follows: The spontaneous MN induction was found significantly higher in whole blood and PBMC cultures for MS patients comparatively to controls. The differences had statistical significance for total lymphocyte population and also for separated CD4+ and CD8+ lymphocytes. No correlation has been observed between the spontaneous MN yield and illness duration for the group of MS patients. No difference in radiosensitivity was observed between patients and controls after 2 Gy irradiation of whole blood. In irradiated PBMC cultures, a slightly lower induction of MN was observed in the case of MS patients. For the MS patients, lymphocyte radiosensitivity was significantly higher in whole blood culture environment compared to PBMC culture environment. The CD4+ lymphocyte subset from MS patients was significantly less radiosensitive compared to healthy controls. On the other hand, CD8+ lymphocytes

  15. Lymphocyte Functions in Space - Related Conditions

    Risin, D.; Sundaresan, A.; Pellis, N. R.; Davson, David L. (Technical Monitor)


    Our previous studies showed that modeled (MMG) and true (STS-54 and STS-56) microgravity (MG) inhibit human lymphocyte locomotion. MMG also suppresses polyclonal and antigen-specific lymphocyte activation. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism localized either at the PKC level or upstream at the cell membrane. FACS analysis of the expression of PKC isoforms in PBMC revealed that MMG selectively inhibits the PKC isoforms expression. The decrease was most prominent in PKC epsilon, less obvious in PKC delta and almost marginal and insignificant in PKC alpha. Western blot analysis confirmed these results (PKC epsilon protein expression was downregulated at 24, 72 and 96 hours in MG). We also found a decrease in PKC epsilon mRNA expression. MMG inhibited programmed cell death (PCD) in lymphocytes. Inhibition was observed in two types of experiments: 1) when PCD was induced by gamma-radiation of PBMC, and 2) when PCD in activated T cells was triggered by PHA-M or PMA + ionomycin restimulation. The established direct effects of MG on signal transduction mechanisms as well as on PCD in lymphocytes could contribute to the impairment of the immunity in space.

  16. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma


    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  17. Defect modelling

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  18. Chemokines, lymphocytes, and HIV

    Farber J.M.


    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

  19. Stages of Chronic Lymphocytic Leukemia

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  20. What Is Acute Lymphocytic Leukemia (ALL)?

    ... White blood cells help the body fight infections. Lymphocytes These are the main cells that make up ... B cells) and T lymphocytes (T cells). B lymphocytes: B lymphocytes protect the body from invading germs ...

  1. Increased radiosensitivity of a subpopulation ot T-lymphocyte progenitors from patients with Fanconi's anemia

    In vitro radiation survival of peripheral blood T lymphocytes was studied in 15 clinically normal adults and 4 patients with Fanconi's anemia. Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and a newly developed whole blood T-lymphocyte colony assay were used to measure lymphocyte blastogenesis and colony formation in response to phytohemagglutinin (PHA) or concanavalin-A (Con-A) stimulation. Lymphocyte colony formation was found to be consistently more sensitive than the LST for detection of low-level radiation effects using both normal cells and lymphocytes from Fanconi's anemia patients. Lymphocytes from patients with Fanconi's anemia were significantly more sensitive to in vitro x-irradiation than lymphocytes from clinically normal individuals as measured by their ability to divide when stimulated by PHA in the LST (patients, D37 . 198 R; normals, D37 . 309 R, p . 0.057) and colony formation assay (patients, D37 . 53 R; normals, D37 . 109 R, p . 0.016). No significant difference in the radiosensitivity of the Con-A response was observed between the two groups. The PHA-responsive T-lymphocyte subpopulation in Fanconi's anemia patients appears to be intrinsically defective. The nature of this defect, significance in the disease process, and relevancy of these findings to the establishment of radiation protection standards are discussed

  2. Cytotoxic T lymphocytes

    Hirohashi, Yoshihiko; Torigoe, Toshihiko; Inoda, Satoko; Morita, Rena; Kochin, Vitaly; Sato, Noriyuki


    Cancer stem cells (CSCs)/cancer-initiating cells (CICs) are characterized as a small population of cancer cells that have high tumor-initiating ability. CSCs/CICs are resistant to several cancer therapies, and eradication of CSCs/CICs is essential to cure cancer. How can we eradicate CSCs/CICs? Cytotoxic T lymphocytes (CTLs) might be a promising answer.

  3. Scaling Aspects of Lymphocyte Trafficking

    Perelson, Alan S.; Wiegel, Frederik W.


    We consider the long lived pool of B and T cells that recirculate through blood, tissues and the lymphatic system of an animal with body mass M. We derive scaling rules (allometric relations) for: (1) the rate of production of mature lymphocytes; (2) the accumulation of lymphocytes in the tissues; (3) the flux of lymphocytes through the lymphatic system; (4) the number of lymph nodes, (5) the number of lymphocytes per clone within a lymph node, and (6) the total number of lymphocytes within a...

  4. Allosuppressor T lymphocytes abolish migration inhibition factor production in autoimmune thyroid disease: evidence from radiosensitivity experiments

    The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al., 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT. (author)

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


    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

  6. Lymphocyte Trafficking to Mucosal Tissues

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


    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 with...

  7. Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma


    Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  8. Radiosensitivities of sensitized lymphocytes

    Immunization of mice with cell antigens such as allogeneic tumor cells or xenogeneic erythrocytes raises a variety of immune reactions mediated by T lymphocytes: i.e. delayed type hypersensitivity (DTH), cytotoxicity, and antibody production. The radiosensitivities of these reactions were examined in mice exposed to 600 R x-irradiation a few hours before or after immunization. 1) DTH to xenogeneic erythrocytes, as demonstrated by footpad reaction, was not suppressed by irradiation 3 h before or after immunization. DTH to allogeneic tumor cells, as demonstrated by a migration inhibition test, hardly developed in mice that had been irradiated before or after immunization. It may have belonged to distinct types of delayed reactions which were mediated by distinct subpopulations of T lymphocytes. 2) Cytotoxicity against allogeneic cells and xenogeneic erythrocytes showed almost the same radiosensitivity. It was scarcely detected in mice that had been irradiated before immunization. However, a low but definite degree of cytotoxicity was detected in mice that had been irradiated only a few hours after immunization. Solubilized allogeneic cells instead of native cells were used as immunizing antigens. It was also possible for precursor cells with cytotoxicity to acquire a radioresistant nature by immunization of solubilized antigens, but native cells were required as stimulation for radioresistant precursor cells to differentiated into nature cytotoxic effector cells. 3) Antibody production against xenogeneic erythrocytes or allogeneic cells was almost completely depleted in mice that had been irradiated before or after immunization. It is possible that antibody production essentially requires cell division and clonal expansion of B lymphocytes. (Bell, E.)

  9. The defect

    Kuhlmann, Franz-Viktor


    We give an introduction to the valuation theoretical phenomenon of "defect", also known as "ramification deficiency". We describe the role it plays in deep open problems in positive characteristic: local uniformization (the local form of resolution of singularities), the model theory of valued fields, the structure theory of valued function fields. We give several examples of algebraic extensions with non-trivial defect. We indicate why Artin-Schreier defect extensions play a central role and describe a way to classify them. Further, we give an overview of various results about the defect that help to tame or avoid it, in particular "stability" theorems and theorems on "henselian rationality", and show how they are applied. Finally, we include a list of open problems.

  10. Lymphocyte migration studies in man

    In this paper the author outlines what is known of the migration and recirculation of the lymphocyte in man and animals. He then attempts to demonstrate how a better grasp of these phenomena may contribute to an understanding of the pathophysiology of human diseases such as chronic lymphocytic leukemia, non-Hodgkin's lymphomas, Hodgkin's, and other diseases

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

    S M Noskov


    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. Radiosensitivity of lymphocytes in vitro

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

  13. Effect on canine lymphocyte function of 144Ce inhaled in fused clay particles

    Beagle dogs exposed by inhalation to 144Ce in fused clay particles develop a persistent lymphopenia and the remaining peripheral lymphocytes in these dogs show a depressed in vitro response to plant mitogens. These studies were designed to evaluate the cellular basis for this defect. The survival and growth of lymphocytes from irradiated and control dogs were evaluated through 96 hours of culture. Many irradiated lymphocytes that were viable in vivo died within 24 hours in vitro. The remaining lymphocytes appeared to grow normally indicating that the early in vitro death was responsible for at least a portion of the difference between irradiated and control lymphocyte cultures. A second experiment was designed to determine if any humoral factors in plasma of irradiated dogs were responsible for the poor response of the lymphocytes. Lymphocytes from irradiated and control dogs were grown with plasma from both types of animals. Heterologous plasma had no apparent effect on lymphocyte growth, indicating that humoral factors were not involved. (U.S.)

  14. Structural and functional changes in lymphocytes in microgravity

    Risin, D.; Risin, S.; Ward, N.; Sundaresan, A.; Pellis, N. R.

    Impairment of the immunity in astronauts and cosmonauts even in short-term flights is a recognized risk. Long-term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Since 1992 we are investigating the effect of modeled (MMG) and true microgravity on isolated lymphocytes in vitro. We had shown that modeled and true microgravity inhibit lymphocyte locomotion. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. At the same time polyclonal lymphocyte activation prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism that was confirmed in further studies. FACS analysis showed that MMG selectively inhibits the expression of PKC isoforms. The decrease was most prominent and substantial in PKC ɛ, less obvious in PKC δ and almost marginal and insignificant in PKC α . Downregulation of PKC isoforms δ and ɛ was proven at the mRNA level by RT-PCR and at protein level by Western blot. We had also demonstrated that MMG selectively affects not only the expression but also the cell distribution of different PKC isoforms that may contribute to the impairment of signal transduction in MG. MMG inhibits programmed cell death (PCD) in lymphocytes. Inhibition was observed in two experimental models (PCD induced by gamma-radiation in PBMC and activation-induced PCD in activated T cells after restimulation with PHA-M or PMA+ionomycin.). Comparative DNA chip analysis has demonstrated a significant difference in gene expression profiles between static and MG analog cultures of activated T cells. (Supported by NRA OLMSA-02 and NSCORT NAG5-4072 grants).

  15. What Is Chronic Lymphocytic Leukemia?

    ... Topic Normal bone marrow, blood, and lymphoid tissue 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 ...

  16. [Chronic lymphocytic leukemia].

    Aoki, Sadao


    Currently, several novel drugs are available for chronic lymphocytic leukemia (CLL) in Western countries. Of these drugs, those that inhibit the B-cell receptor (BCR) signaling pathway are the most promising. Ibrutinib inhibits BTK in the BCR pathway and can be administered orally. The results of several clinical trials suggest that ibrutinib is highly effective against relapsed/resistant (RR) and treatment-naïve CLL. Furthermore, ibrutinib shows equivalent efficacy on CLL with the 17p deletion. Idelalisib, which also blocks the BCR pathway, inhibits PIK3delta and induces CLL cell death. Clinical trials have shown outstanding efficacy of idelalisib against RR-CLL, especially when administered with antiCD20 antibodies. This drug is also effective against CLL with the 17p deletion. ABT-199 is another novel drug; it inhibits BCL2 signaling, not the BCR pathway, and can be administered orally. The efficacy of ABT-199 against RR-CLL has been demonstrated in a number of clinical trials. These drugs have only mild toxicity and can be used for patients in poor general condition. Unfortunately, none of these drugs have yet been approved in Japan. Rapid resolution of the 'drug lag' problem is necessary. PMID:27076234

  17. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    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. (author)

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

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


    @@ 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.

  19. Human diseases associated with defective DNA repair

    The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

  20. PARP1-Driven Apoptosis in Chronic Lymphocytic Leukemia


    Chronic lymphocytic leukemia (CLL) is considered a malignancy resulting from defects in apoptosis. For this reason, targeting apoptotic pathways in CLL may be valuable for its management. Poly [ADP-ribose] polymerase 1 (PARP1) is the main member of a family of nuclear enzymes that act as DNA damage sensors. Through binding on DNA damaged structures, PARP1 recruits repair enzymes and serves as a survival factor, but if the damage is severe enough, its action may lead the cell to apoptosis thro...

  1. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  2. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  3. Opinion: Interactions of innate and adaptive lymphocytes

    Gasteiger, Georg; Rudensky, Alexander Y.


    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a mo...

  4. Lymphocyte receptors for pertussis toxin

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

  5. Recurrent abortions and lymphocyte transfusions.

    Bjercke, S


    Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo. PMID:8009967

  6. The course of lymphocytic hypophysitis.

    Bitton, R N; Slavin, M; Decker, R E; Zito, J; Schneider, B S


    A 27-year-old woman presented to our institution in her seventh month of pregnancy with complaints of headache and visual field disturbance. Workup revealed bitemporal hemianopia, a markedly enlarged pituitary gland on computed tomography scan, and biochemical evidence of partial hypopituitarism. At surgery, a biopsy specimen of the pituitary gland was taken revealing lymphocytic hypophysitis. The patient was treated with steroids and replacement doses of thyroid hormone. Visual fields improved postoperatively. A repeat computed tomography scan obtained 2 months after an uneventful pregnancy showed that her pituitary had regained normal size and contour. Over the next 9 months she had gradual recovery of all pituitary function. This case allowed us to follow and document the course of lymphocytic hypophysitis from its presentation as a macroadenoma with partial hypopituitarism to full recovery of both size and hormonal function of the pituitary. Lymphocytic hypophysitis should be considered in the differential diagnosis of a pituitary mass or pituitary dysfunction presenting in pregnancy. In patients with suspected lymphocytic hypophysitis and a pituitary mass, a trial of steroids may be therapeutic. PMID:2053072

  7. Radiosensitivity of lymphocytes among Filipinos: final report

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

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


    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

  9. Ibrutinib or Idelalisib in Treating Patients With Persistent or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma After Donor Stem Cell Transplant


    Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma

  10. Repair of x-ray induced chromosomal damage in trisomy 2- and normal diploid lymphocytes

    The frequency of chromosomal aberrations produced by x-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells

  11. Neural Tube Defects

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

  12. Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers

    It has been postulated that host immune defects are responsible for the development and persistence of the hepatitis B surface antigen (HBsAg) carrier state. The synthesis of both anti-HBs and antibody to hepatitis B core antigen (anti-HBc) in cultures containing peripheral blood mononuclear cells from chronic HBsAg carriers and from control (antibody-positive) patients was measured in the presence of pokeweed mitogen. Similar amounts of polyclonal IgG and IgM were synthesized by cultures containing lymphocytes from chronic carriers and controls. Anti-HBc was detectable in lymphocyte supernatants from 2 of 20 controls and from 21 of 29 carriers. The presence of anti-HBc synthesis in vitro correlated with high serum titers of anti-HBc. In contrast, anti-HBs was detected in lymphocyte supernatants from 6 of 20 controls (predominantly in those who had high serum titers of anti-HBs) but in none of the supernatants from 29 HBsAg carriers. Co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated (''helper'') T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc but still did not synthesize detectable amounts of anti-HBs. In the converse experiments, B lymphocytes from controls were co-cultured with irradiated T lymphocytes from carriers. The T lymphocytes from 16 of 24 carriers augmented anti-HBs production by control B cells normally, the remaining eight did not. Finally, mixtures of control B cells and control irradiated T lymphocytes were co-cultured with T lymphocytes from chronic HBsAg carriers. 5 of 12 carriers demonstrated active suppression of anti-HBs production, and in three this suppression was specific, as IgG and IgM production remained normal

  13. Signal integration during T lymphocyte activation and function: lessons from the Wiskott-Aldrich syndrome

    Vinícius eCotta-de-Almeida


    Full Text Available Over the last decades, research dedicated to the molecular and cellular mechanisms underlying Primary immunodeficiencies (PID has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20 years on T lymphocytes from Wiskott-Aldrich syndrome (WAS patients. WAS T lymphocytes are defective for the WAS protein (WASP, a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, signaling, as well as the implementation of helper, regulatory and cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology.

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

    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


    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

  15. Lymphocyte migration and radiation lymphopenia

    Ekstrand, K.E.; Plunkett, S.; Heise, E.R.; Dixon, R.L.; Raben, M.


    The dose received by suppressor and helper T lymphocyte suppopulations during a course of pelvic radiation therapy is calculated, taking into account variances in the migration pattern of the two cell types. It is found that the difference in the calculated dose may explain the apparent paradox that the cell type, which is found to be more radioresistant in vitro, is more depleted by the in vivo irradiation.

  16. Lymphocyte migration and radiation lymphopenia

    The dose received by suppressor and helper T lymphocyte suppopulations during a course of pelvic radiation therapy is calculated, taking into account variances in the migration pattern of the two cell types. It is found that the difference in the calculated dose may explain the apparent paradox that the cell type, which is found to be more radioresistant in vitro, is more depleted by the in vivo irradiation

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

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

  18. Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma


    Anemia; Fever, Sweat, and Hot Flashes; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; Weight Change

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

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

  20. Lymphocyte migration into syngeneic implanted lymph nodes

    To judge the functional activity of lymphocytes of an implanted lymph node (LN), the proliferative response of lymphocytes of the implanted organ in the blast-transformation reaction in vitro and their ability to induce a local graft versus host reaction (GVHR) were determined. The lymphocyte suspension for labeling with 51Cr was obtained from peripheral LN in different situations from syngeneic mice. The resulting lymphocyte suspension was labeled with a solution of sodium chromate-51Cr in a concentration of 20-40 microCi/100.106 cells in 1 ml for 40 min at 370C. The proliferative activity of a suspension of lymphocytes was estimated as incorporation of 3H-thymidine into DNA during incubation of the cell suspension for 3 days. Data on migration of 51Cr-labeled cells and the results of the morphological observations revealed marked ability of lymphocytes of the peripheral pool to colonize the regenerating stroma

  1. Do lampreys have lymphocytes? The Spi evidence

    Shintani, Seikou; Terzic, Janos; Sato, Akie; Saraga-Babic, Mirna; O'hUigin, Colm; Tichy, Herbert; Klein, Jan


    It is generally accepted that living jawless vertebrates (lampreys and hagfishes) lack the capability of mounting an adaptive immune response. At the same time, however, there are reports describing histological evidence for the presence in agnathan tissues of lymphocytes, the key players in adaptive immunity. The question therefore arises whether the cells identified morphologically as lymphocytes are true lymphocytes in terms of their genetic developmental program. In this study, evidence i...

  2. Human lymphocyte production of immunoreactive thyrotropin.

    Smith, E M; Phan, M.; Kruger, T E; Coppenhaver, D H; Blalock, J E


    Interferon-alpha inducers were previously shown to cause human lymphocyte production of a corticotropin (ACTH)-like peptide. Thyrotropin (TSH) was not produced under these conditions. In contrast, this report shows that a T-cell mitogen (staphylococcal enterotoxin A), which does not induce the ACTH-like peptide, caused human lymphocyte production of an immunoreactive (ir) TSH. Lymphocyte synthesis of the ir TSH was first detectable at 24 hr, peaked at 48 hr, and thereafter declined. NaDodSO4/...

  3. Lymphocytic Thrombophilic Arteritis Induced by Minocycline

    Kassardjian, Michael; Horowitz, David; Shitabata, Paul K.; Clark, Lani E.


    Lymphocytic thrombophilic arteritis is an entity only recently defined in the literature. This term describes a distinctive histopathological combination of lymphocytic vascular inflammation associated with a hyalinized fibrin ring in the vessel lumina, changes reflecting a thrombophilic endovasculitis. The authors present the case of a woman who developed lymphocytic thrombophilic arteritis coinciding with the use of minocycline. In addition to these histopathological findings, the cutaneous...

  4. Splenic lymphoma with circulating villous lymphocytes.

    Imbing, F; Kumar, D.; Kumar, S.; Yuoh, G; Gardner, F


    This report describes the occurrence of splenic lymphoma with villous lymphocytes (SLVL) in a 56 year old white female with a family history of chronic lymphocytic leukaemia. Other unusual features included a marked lymphocytosis with counts up to 224 x 10(9)/l and marked clumping of lymphocytes in EDTA anticoagulated blood. The neoplastic cells were CD19+, CD20+, CD22+, CD22+, IgM+, lambda+, kappa-, CD5-, and CD10-. The spleen had nodular infiltrates of B lymphocytes in the region of the whi...

  5. Effects of irradiation on normal human lymphocytes

    After the normal human blood was exposured to 60Co gamma-rays, neutrons and X-ray with different doses, the human lymphocytes induced by PHA, ConA, LPS and PWM were cultured in vitro. The proliferation and differentiation kinetics of human lymphocytes were studied by using 3H-TdR, 14C-UR and 14C-valine incorporation technique. The irradiation inhibition on syntheses of DNA, RNA and protein was observed. The results from the experiments showed: (1) The proliferation and differentiation of human lymphocytes, different lymphocytes subgroups, induced by various mitogens were different. (2) The injury effects of irradiation on synthese of DNA and protein in the lymphocytes stimulated with ConA and PHA were greater than that in the lymphocytes induced by LPS and PWM. (3) The injury effect of lymphocytes irradiated by neutrons was greater than that lymphocytes irradiated by gamma-rays and X-rays. (4) In the irradiated human lymphocytes subgroups induced by various mitogens, the more ability of repairing broken DNA strand subgroup had, the more strong resistance to irradiation it was

  6. Autoimmune hepatitis in association with lymphocytic colitis.

    Cronin, Edmond M


    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.

  7. Ontogeny of Innate T Lymphocytes – Some Innate Lymphocytes are More Innate than Others

    Vermijlen, David; Prinz, Immo


    Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is “innate” in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as natural killer (NK) cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune respo...

  8. Ontogeny of innate T lymphocytes - some innate lymphocytes are more innate then others

    David eVermijlen; Immo ePrinz


    Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is innate in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as NK cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, gen...

  9. Noninvasive diagnostics of mitochondrial disorders in isolated lymphocytes with high resolution respirometry

    Petr Pecina; Hana Houšťková; Tomáš Mráček; Alena Pecinová; Hana Nůsková; Markéta Tesařová; Hana Hansíková; Jan Janota; Jiří Zeman; Josef Houštěk


    Background: Mitochondrial diseases belong to the most severe inherited metabolic disorders affecting pediatric population. Despite detailed knowledge of mtDNA mutations and progress in identification of affected nuclear genes, diagnostics of a substantial part of mitochondrial diseases relies on clinical symptoms and biochemical data from muscle biopsies and cultured fibroblasts. Methods: To investigate manifestation of oxidative phosphorylation defects in isolated lymphocytes, digitonin-p...

  10. BRCA1 function in T lymphocytes: a cellular specificity of a different kind

    Gardner, Kevin; Liu, Edison T


    Recent work by Mak et al demonstrates that mice carrying a T-cell-specific disruption of the brca1 gene display markedly impaired T-lymphocyte development and proliferation in the absence of any increased tendency for the formation of tumors. Interestingly, the extent of these defects was found to be highly dependent on cellular context. Contrasting the rather broad tissue expression pattern of brca1 against its exquisitely selective etiologic role in cancers of the breast and ovary, many of ...

  11. Lymphocyte apoptosis in murine Pneumocystis pneumonia

    Ruan Sanbao


    Full Text Available Abstract Background Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs. Methods Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins. Results In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim. Conclusion Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.

  12. Canine lymphocyte activating factor (LAF)

    The immune response of an animal is the sum of the result of the interaction of various cells mainly through soluble mediators. It is not enough to look at specific cell populations, it is also necessary to study the interactions between purified cell population. The effect of one subpopulation on another is via soluble mediators. We have been studying one (of several) such mediators in its relation to radiation effects on the immune response. Lymphocyte activating factor (LAF) is defined functionally as a potentiator of the response of thymocytes to phytohemagglutinin (PHA) or concanavalin (con-A). It can also elicit response of unstimulated subpopulations separated from the thymus. It is a product of adherent populations, presumably macrophages. It has been shown to be produced by human, rabbit, and mouse cells, but has not been reported in the dog. It also was shown to be present in higher concentrations in irradiated mice than in comparable unirradiated mice. We have shown that LAF is produced by plastic-adherent populations derived from peripheral blood. Currently we are working to determine the lymphocyte subpopulations with which LAF interacts

  13. Overexpression of Bmi1 in Lymphocytes Stimulates Skeletogenesis by Improving the Osteogenic Microenvironment

    Zhou, Xichao; Dai, Xiuliang; Wu, Xuan; Ji, Ji; Karaplis, Andrew; Goltzman, David; Yang, Xiangjiao; Miao, Dengshun


    To investigate whether overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by improving the osteogenic microenvironment, we examined the skeletal phenotype of EμBmi1 transgenic mice with overexpression of Bmi1 in lymphocytes. The size of the skeleton, trabecular bone volume and osteoblast number, indices of proliferation and differentiation of bone marrow mesenchymal stem cells (BM-MSCs) were increased significantly, ROS levels were reduced and antioxidative capacity was enhanced in EμBmi1 mice compared to WT mice. In PTHrP1–84 knockin (PthrpKI/KI) mice, the expression levels of Bmi1 are reduced and potentially can mediate the premature osteoporosis observed. We therefore generated a PthrpKI/KI mice overexpressing Bmi1 in lymphocytes and compared them with PthrpKI/KI and WT littermates. Overexpression of Bmi1 in PthrpKI/KI mice resulted in a longer lifespan, increased body weight and improvement in skeletal growth and parameters of osteoblastic bone formation with reduced ROS levels and DNA damage response parameters. Our results demonstrate that overexpression of Bmi1 in lymphocytes can stimulate osteogenesis in vivo and partially rescue defects in skeletal growth and osteogenesis in PthrpKI/KI mice. These studies therefore indicate that overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by inhibiting oxidative stress and improving the osteogenic microenvironment. PMID:27373231

  14. Giardia induces proliferation and interferon γ production by intestinal lymphocytes

    Ebert, E


    BACKGROUND—Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown. 
AIMS—To examine giardia induced proliferation, interferon γ production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood. 
METHODS—Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise ...

  15. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina;


    were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative...... risks (RRs), eg, mucinous differentiation (RR, 9.0), tumor-infiltrating lymphocytes (RR, 7.5), absence of necrosis (RR, 7.5), and expanding growth pattern (RR, 5.0) into a 7-factor index, the presence of at least 4 features identified the MMR-defective tumors with 92.3% sensitivity and 75.3% specificity...

  16. Facts about Birth Defects

    ... Us Information For... Media Policy Makers Facts about Birth Defects Language: English Español (Spanish) Recommend on Facebook Tweet ... having a baby born without a birth defect. Birth Defects Are Common Every 4 ½ minutes, a baby ...

  17. Defect production in ceramics

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


    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.

  18. Defect production in ceramics

    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 Si3N4), 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

  19. Defect production in ceramics

    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 AlN and Si3N4), 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. (orig.)

  20. Sudden unexpected death associated with lymphocytic thyroiditis

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


    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...

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

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


    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.

  2. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    Çiğdem Usul Afşar; Semra Paydaş; Meral Günaldı; Berna Bozkurt Duman; Vehbi Erçolak; Suzan Zorludemir; Arbil Açıkalın


    Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) which is a relatively rare co-occurrence. Conflict of interest:None declared.

  3. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    Çiğdem Usul Afşar


    Full Text Available Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL which is a relatively rare co-occurrence.

  4. 21 CFR 864.8500 - Lymphocyte separation medium.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8500 Lymphocyte separation medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes...

  5. Lymphocytes from the site of disease but not blood lymphocytes indicate the cause of arthritis.

    Ford, D K; da Roza, D; Schulzer, M


    The [3H]thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial effusions and from peripheral blood. The stimulating antigens were crude preparations of those micro-organisms that are related to the enteritis and the non-gonococcal urethritis that precipitate reactive arthritis. Salmonella, shigella, and campylobacter antigens stimulated synovial but not peripheral blood lymphocytes in eight cases of enteric reactive arthriti...

  6. The influence of leptin on the activity of lung lymphocytes under simulated microgravity.

    Li, Xu; Liu, Chang-Ting; Zhou, Hong


    Exposure to microgravity has been implicated in the compromised immune function in space travellers, resulting in opportunistic infections, poor wound healing, and cancer. Since recent studies have suggested that leptin was capable of modulating immune responses, the purpose of this study was to examine effects of microgravity on the activation and proliferation of rat lung lymphocytes and then to examine the effects of leptin-mediated signal transduction mechanisms of lymphocyte activation in these same conditions. In control conditions (T-flasks cultured cells) leptin was not able by itself to increase lymphocytes proliferation, or induce significant increase of either IL-2 production or expression of lymphocytes activation markers, such as CD25 and CD71, while it markedly enhanced the positive effects induced on these parameters by concanavalin A (ConA). Using clinostatic rotating wall vessel (RWV) bioreactors to simulate a microgravity environment, we found that ConA responsiveness was inhibited. Moreover, under these conditions, leptin was not able to reverse these impaired functions. Accordingly with the above cited inhibitory effects exerted by the simulated microgravity environment, evidence was also obtained of defects in lymphocyte intracellular signal transduction induced by the incubation in RWV bioreactors, namely concerning decreased ConA-mediated PKC activity, and reduced expression of NF-kappaB, c-fos, and ERK1/2. Again, leptin appeared to be unable in restoring a physiologic increase of these parameters, different from what could be observed after complementation of the ConA-mediated signalling with phorbol myristate acetate, which instead demonstrated to overcome the inhibition of lymphocytes activating functions, in the presence of simulated microgravity conditions. PMID:19626337

  7. Metal ion levels and lymphocyte counts

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


    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 of...

  8. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... acute lymphocytic leukemia in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

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

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


    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...


    E. V. Abakushina


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

  11. Ontogeny of innate T lymphocytes - some innate lymphocytes are more innate then others

    David eVermijlen


    Full Text Available Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is innate in lymphocytes. Lymphocytes without V(DJ-rearranged antigen receptors are now termed innate lymphoid cells (ILCs and include cells formerly known as NK cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, genuine innate lymphocytes would be present before or at birth. Here we review the ontogeny of human and mouse innate T lymphocyte populations. We focus on γδ T cells, which are prototype lymphocytes that often use their V(DJ rearrangement machinery to generate genetically encoded predetermined recombinations of antigen receptors. We make parallels between the development of γδ T cells with that of innate aβ T cells (invariant (iNKT and mucosa-associated invariant T (MAIT cells and compare this with the ontogeny of innate B cells and innate lymphoid cells (ILCs, including NK cells. We conclude that some subsets are more innate than others, i.e. innate lymphocytes that are made primarily early in utero during gestation while others are made after birth. In practice, a ranking of innateness by ontogeny has implications for the reconstitution of innate lymphocyte subsets after hematopoietic stem cell transplantation (HSCT.

  12. Lymphocytic hypophysitis and hypothalamitis - a case report

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

  13. Lymphocyte dysfunction in congenital hypoplastic anemia.

    Finlay, J. L.; Shahidi, N T; Horowitz, S; Borcherding, W; Hong, R


    Congenital hypoplastic anemia (Diamond-Blackfan syndrome) is thought to involve the erythropoietic cell line alone. In this study, the evaluation of lymphocyte function in five patients with this syndrome revealed a number of abnormalities. Peripheral blood T lymphocyte percentages as assessed by monoclonal antibodies were decreased in three patients. T-helper/T-suppressor cell (OKT4:OKT8) ratios were almost unity in four of the five patients. We usually find a ratio of 2:1 in normal populati...

  14. Chemotaxis of large granular lymphocytes

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

  15. Imaging defects and dopants

    H.Philipp Ebert


    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.

  16. Defects in semiconductors

    Romano, Lucia; Jagadish, Chennupati


    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

  17. Hypertrophic gastropathy with gastric adenocarcinoma: Menetrier's disease and lymphocytic gastritis?

    Mosnier, J F; Flejou, J F; Amouyal, G; Gayet, B; Molas, G.; Henin, D; Potet, F


    Lymphocytic gastritis is a form of gastric inflammation characterised by a pronounced increase in lymphocytes in gastric surface and foveolar epithelium. Lymphocytic gastritis is often associated with endoscopic evidence of 'varioliform gastritis'. Lymphocytic gastritis has recently been reported to be associated with other forms of hypertrophic gastropathies. We present a case of hypertrophic gastropathy with gastric adenocarcinoma, with both Menetrier's disease and lymphocyte gastritis. Imm...

  18. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia


    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  19. School Building Defect Pattern

    Mahli M.


    Full Text Available In providing a conducive learning environment for the student, the school building must be in good condition. This paper is evaluating the existing condition of primary school building in Sarawak, Malaysia. It focuses on building defects pattern for school building. The primary data collection is from the school building condition survey with involvement of 24 primary schools. The schools have been selected using simple random sampling and stratified sampling (of school age as the variable of selection. The reporting method is based on Condition Survey Protocol (CSP 1 Matrix. Data analysis covers descriptive and inferential statistics. The analysis carried out found that the overall 4,725 defects have been identified. The building defect pattern is mainly on Ground Level of 3,176 defects, the highest number of defects components found on walls (798. 16.2% defects are cracks from 11 common defects and most of all the highest score of defects based on age of the building were the building in the range of 11 to 20 years.

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

    Hokland, M; Hokland, P; Heron, I;


    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...

  1. Defects at oxide surfaces

    Thornton, Geoff


    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...

  2. Cosmic defects and cosmology

    Magueijo, J; Magueijo, Joao; Brandenberger, Robert


    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...

  3. Characterization of the atypical lymphocytes in African swine fever

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


    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

  4. Overlapping functions between XLF repair protein and 53BP1 DNA damage response factor in end joining and lymphocyte development.

    Liu, Xiangyu; Jiang, Wenxia; Dubois, Richard L; Yamamoto, Kenta; Wolner, Zachary; Zha, Shan


    Nonhomologous end joining (NHEJ), a major pathway of DNA double-strand break (DSB) repair, is required during lymphocyte development to resolve the programmed DSBs generated during Variable, Diverse, and Joining [V(D)J] recombination. XRCC4-like factor (XLF) (also called Cernunnos or NHEJ1) is a unique component of the NHEJ pathway. Although germ-line mutations of other NHEJ factors abrogate lymphocyte development and lead to severe combined immunodeficiency (SCID), XLF mutations cause a progressive lymphocytopenia that is generally less severe than SCID. Accordingly, XLF-deficient murine lymphocytes show no measurable defects in V(D)J recombination. We reported earlier that ATM kinase and its substrate histone H2AX are both essential for V(D)J recombination in XLF-deficient lymphocytes, despite moderate role in V(D)J recombination in WT cells. p53-binding protein 1 (53BP1) is another substrate of ATM. 53BP1 deficiency led to small reduction of peripheral lymphocyte number by compromising both synapse and end-joining at modest level during V(D)J recombination. Here, we report that 53BP1/XLF double deficiency blocks lymphocyte development at early progenitor stages, owing to severe defects in end joining during chromosomal V(D)J recombination. The unrepaired DNA ends are rapidly degraded in 53BP1(-/-)XLF(-/-) cells, as reported for H2AX(-/-)XLF(-/-) cells, revealing an end protection role for 53BP1 reminiscent of H2AX. In contrast to the early embryonic lethality of H2AX(-/-)XLF(-/-) mice, 53BP1(-/-)XLF(-/-) mice are born alive and develop thymic lymphomas with translocations involving the T-cell receptor loci. Together, our findings identify a unique function for 53BP1 in end-joining and tumor suppression. PMID:22355127

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

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


    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

  6. Ultraviolet-induced DNA excision repair in human B and T lymphocytes. 3. Repair in lymphocyte from chronic lymphocytic leukaemia

    This study examined the capacity of lymphocytes from individuals with chronic lymphocytic leukaemia (CLL) to undertake ultraviolet (u.v.)-induced DNA repair in comparison to control and age-matched purified B and T lymphocytes. The technique was independent of incorporation of radioactive precursor, i.e. by the recovery of normal sedimentation behaviour of nucleoid bodies obtained from these cells by lysis in high salt and non-ionic detergent. Recovery of normal sedimentation was associated with restoration of DNA supercoiling. CLL cells were found to be as sensitive to u.v. and to repair at similar rates as age-matched B controls. They were considerably more sensitive than young B cells and repaired less efficiently. Reasons for previous reported discrepancies in CLL repair were discussed. (author)

  7. Software Defect Association Mining and Defect Correction Effort Prediction

    Song, Q; Shepperd, MJ; Cartwright, MH; Mair, C.


    Much current software defect prediction work concentrates on the number of defects remaining in software system. In this paper, we present association rule mining based methods to predict defect associations and defect-correction effort. This is to help developers detect software defects and assist project managers in allocating testing resources more effectively. We applied the proposed methods to the SEL defect data consisting of more than 200 projects over more than 15 years. The results s...

  8. Radiation survival curve parameters for human lymphocytes

    This paper estimates radiation survival curve parameters for lymphocytes in order to optimize large-field radiation schedules for patients with lymphoma or patients requiring immunosuppression. The authors compared radiation schedules (total body or total lymphoid) used in 12 different studies in dogs, pigs, rhesus monkeys, or human patients. Different radiation schedules should cause the same survival fraction for lymphocytes if results are similar and cause at least a threefold difference in survival fractions if results are dissimilar. By trial and error, the best extrapolation number (n) and D0 can be selected for each data set by using the single-hit, multiple-target model. Data sets are best explained by postulating an n of 1.25-1.50 and a D0 of 1.5 Gy for malignant (B lymphocytes) or normal lymphocytes. Both are higher than previous estimates made by other investigators determining lymphocyte numbers in peripheral blood after radiation exposure or by using radiation conditions unrealistic for human patients that can be achieved only in small rodents

  9. Neural tube defects

    M.E. Marshall


    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 bee...

  10. Defect solitons in photonic lattices.

    Yang, Jianke; Chen, Zhigang


    Nonlinear defect modes (defect solitons) and their stability in one-dimensional photonic lattices with focusing saturable nonlinearity are investigated. It is shown that defect solitons bifurcate out from every infinitesimal linear defect mode. Low-power defect solitons are linearly stable in lower bandgaps but unstable in higher bandgaps. At higher powers, defect solitons become unstable in attractive defects, but can remain stable in repulsive defects. Furthermore, for high-power solitons in attractive defects, we found a type of Vakhitov-Kolokolov (VK) instability which is different from the usual VK instability based on the sign of the slope in the power curve. Lastly, we demonstrate that in each bandgap, in addition to defect solitons which bifurcate from linear defect modes, there is also an infinite family of other defect solitons which can be stable in certain parameter regimes. PMID:16605473

  11. Screening Tests for Birth Defects

    ... Management Education & Events Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search ... for Birth Defects FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a ...

  12. Defect forces, defect couples and path integrals

    Definition and meaning of concepts like 'J integral' are given without any assumption about material behaviour. The key of the work is the field of 'defect forces' and 'defect couples' in a continuous media. These forces and couples, which can also be called 'material forces' and 'material couples' are related to the work done by a particle moving through a solid. It is shown that the resultant of all the defect forces included in a volume is the Jsub(k) integral computer on the surface surrounding this volume. A similar result is obtained about the moment resultant. Conventional form of the principle of virtual work is not applicable to fractures mechanics because equations of compatibility are not satisfied. A generalized form is given, which is valid when (virtual) crack propagation is considered. The virtual work of 'material' forces is included in the generalized form, and can be used as a new definition of J concept. As an illustration application, a simple procedure is described which allows to obtain the curve J-Δa (the so called J-R curve) from only one experimental test

  13. T cell immunity using transgenic B lymphocytes

    Gerloni, Mara; Rizzi, Marta; Castiglioni, Paola; Zanetti, Maurizio


    Adaptive immunity exists in all vertebrates and plays a defense role against microbial pathogens and tumors. T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells and differentiate into effector cells. Currently, dendritic cells are considered the only cells capable of stimulating T lymphocytes. Here, we show that mature naïve B lymphocytes can be genetically programmed by using nonviral DNA and turned into powerful antigen-presenting cells with a dual capacity of synthesis and presentation of antigen to T cells in vivo. A single i.v. injection of transgenic lymphocytes activates T cell responses reproducibly and specifically even at very low cell doses (102). We also demonstrate that T cell priming can occur in the absence of dendritic cells and results in immunological memory with protective effector functions. These findings disclose aspects in the regulation of adaptive immunity and indicate possibilities for vaccination against viruses and cancer in humans.

  14. Temperature effects on lymphocyte transformation invitro.

    Hirsch, R L; Jeffries, B D; Gray, I


    Phytohemagglutinin (PHA)-induced transformation of normal rat peripheral lymphocytes has been studied at a wide range of culture temperatures (4 degrees C to 42 degrees C). Lymphocyte transformation was maximum at 37 degrees C while insignificant stimulation was observed between 4 degrees C and 30 degrees C. Temperatures above 37 degrees C produced sub=optimal transformation as measured by synthesis of DNA and protein, and appearance of lymphoblasts. Binding studies using 125I-PHA indicate that the low temperature inhibition of lymphocyte transformation could be a result of excess lectin (being available as a result of low temperature) bound to the cell surface, preventing the initiation of the molecular events associated with transformation. PMID:863471

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

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


    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.

  16. Defect Prevention Based on 5 Dimensions of Defect Origin

    Sakthi Kumaresh


    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


    Pavankumar Tandra


    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

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

    Veronica eMarrella


    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.

  19. Birth Defects (For Parents)

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... there is a problem with a baby's body chemistry, it is called a metabolic birth defect. Metabolic ...

  20. Neural tube defects

    M.E. Marshall


    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. Point defects in platinum

    An investigation was made of the mobility and types of point defect introduced in platinum by deformation in liquid nitrogen, quenching into water from 1600oC, or reactor irradiation at 50oC. In all cases the activation energy for motion of the defect was determined from measurements of electrical resistivity. Measurements of density, hardness, and x-ray line broadening were also made there applicable. These experiments indicated that the principal defects remaining in platinum after irradiation were single vacant lattice sites and after quenching were pairs of vacant lattice sites. Those present after deformation In liquid nitrogen were single vacant lattice sites and another type of defect, perhaps interstitial atoms. (author)

  2. Lymphocyte subpopulation in acute viral hepatitis.

    Datta, U; Sehgal, S.; Pal, S. R.; Dhall, K; Singh, S.; Datta, D. V.


    Studies of peripheral blood lymphocytes were performed in 41 patients with acute viral hepatitis, in grade III-IV coma; 16 patients were in the third trimester of pregnancy. There were significant reductions in absolute lymphocyte count and T cell number in patients who succumbed to the disease, when compared with those who survived. B cell counts were similar in the two groups and migration inhibition test with BCG antigen was normal. It is postulated that a decrease in the number of cells i...

  3. Quantum computing with defects

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


    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 qua...

  4. Anomalies and developmental defects

    Amonalies and developmental defects in trachea and bronchi (tracheal bronch us, diverticulum of trachea or bronchus, defects due to atresia of bronchial tre e, tracheobronchomegaly), lung vessels (aneurisms of pulmonary artery, agenesia, aplasia and hypoplasia of pulmonary artery,anomalies of pulmonary veins, varico sis of pulmonary veins), pulmonary tissue (lung sequestration, congenital lobar pulmonary emphysema, essential hemosiderosis), have beendescribed. The problems of the diagnosis of the above-mentioned diseases using roentgenograms are consid ered

  5. Neural Tube Defects

    Greene, Nicholas D. E.; Copp, Andrew J.


    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechani...

  6. Signatures of Topological Defects

    Berezinsky, V. S.; P. Blasi(INAF Arcetri); Vilenkin, A.


    We argue that due to various restrictions cosmic strings and monopole-string networks are not likely to produce the observed flux of ultra-high energy cosmic rays (UHECR). Among the topological defects studied so far, the most promising UHECR sources are necklaces and monopolonia. Other viable sources which are similar to topological defects are relic superheavy particles. All these sources have an excess of pions (and thus photons) over nucleons at production. We demonstrate that in the case...

  7. Do We Know What Causes Chronic Lymphocytic Leukemia?

    ... Topic Can chronic lymphocytic leukemia be prevented? Do we know what causes chronic lymphocytic leukemia? The exact ... genes -- the instructions for how our cells function. We look like our parents because they are the ...

  8. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    ... treatment for acute lymphocytic leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is ... with your doctor. You should feel free to ask any question that’s on your mind, no matter ...

  9. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

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


    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...

  10. GABA, a natural immunomodulator of T lymphocytes

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida;


    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 be...

  11. Regulatory T-lymphocytes in asthma

    van Oosterhout, AJM; Bloksma, N


    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

  12. In vitro responsiveness of lymphocytes to phytohemmagglutinin.

    Peterson, M L; Rommo, N; House, D; Harder, S


    Peripheral blood lymphocytes from 20 human subjects exposed to 784 microgram/m3 ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response to PHA (normal response is proliferation of lymphocytes) was significantly suppressed (P less than .01) in samples obtained immediately after subjects' exposure to ozone. Recovery of response occurred 2 weeks postexposure. Responses were unchanged in subjects exposed to clean air. Existing studies suggest that ozone exposure may generate free radicals or other reactive molecules or both, that could be responsible for immediate changes in metabolic events leading to blockage or inhibition of deoxyribonucleic acid (DNA) synthesis in T lymphocytes as shown in this study. It is possible that some prerequisite to active cell metabolism such as ribonucleic acid (RNA) may be impaired by ozone exposure. The significance of the suppression of T-cell response noted in this study is that: (1) if continuous exposures to ozone are shown to induce an immunosuppressed state for a significant time period, an important factor in carcinogenesis might be elucidated; (2) immunosuppression may cause a progression of an already present tumor; (3) immunosuppression may enable endogenous latent infections such as tuberculosis to reactivate; and (4) immunosuppression may explain in part the relationship between chronic oxidant air pollution and influenza-like illnesses in population. PMID:646458

  13. The lymph node in chronic lymphocytic leukemia.

    Dick, F R; Maca, R D


    Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic-histiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survival. PMID:580071

  14. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  15. Birth Defects. Matrix No. 2.

    Brent, Robert L.

    This report discusses the magnitude of the problem of birth defects, outlines advances in the birth defects field in the past decade, and identifies those areas where research is needed for the prevention, treatment, and management of birth defects. The problem of birth defects has consumed a greater portion of our health care resources because of…

  16. Hodgkin lymphoma transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

    Krause, John R.; Drinkard, Lee C.; Keglovits, Latoya C.


    Transformation to a large cell lymphoma may occur during the course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in approximately 5% of the cases. This is known as Richter's transformation. A much less frequent transformation to Hodgkin lymphoma may occur. We report a case of CLL/SLL in which a transformation to Hodgkin lymphoma occurred, and we review previously published reports of this transformation. Transformation to Hodgkin lymphoma in CLL/SLL has a poor outcome ...


    Rudolf Mišičko; Tibor Kvačkaj; Martin Vlado; Lucia Gulová; Miloslav Lupták; Jana Bidulská


    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...

  18. Supersymmetric k-defects

    Koehn, Michael; Trodden, Mark


    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.

  19. Dysregulation of T lymphocyte proliferative responses in autoimmunity.

    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.

  20. PARP1-Driven Apoptosis in Chronic Lymphocytic Leukemia

    Panagiotis T. Diamantopoulos


    Full Text Available Chronic lymphocytic leukemia (CLL is considered a malignancy resulting from defects in apoptosis. For this reason, targeting apoptotic pathways in CLL may be valuable for its management. Poly [ADP-ribose] polymerase 1 (PARP1 is the main member of a family of nuclear enzymes that act as DNA damage sensors. Through binding on DNA damaged structures, PARP1 recruits repair enzymes and serves as a survival factor, but if the damage is severe enough, its action may lead the cell to apoptosis through caspase activation, or necrosis. We measured the PARP1 mRNA and protein pretreatment levels in 26 patients with CLL and the corresponding posttreatment levels in 15 patients after 3 cycles of immunochemotherapy, as well as in 15 healthy blood donors. No difference was found between the pre- and posttreatment levels of PARP1, but we found a statistically significant relative increase of the 89 kDa fragment of PARP1 that is cleaved by caspases in the posttreatment samples, indicating PARP1-related apoptosis in CLL patients after treatment. Our findings constitute an important step in the field, especially in the era of PARP1 inhibitors, and may serve as a base for future clinical trials with these agents in CLL.

  1. Studies on lymphocyte function in gynecological cancer patients, 2

    In the second of these three serial studies the effects of therapeutic Co60 irradiation on the lymphocytes were examined with special reference to their reactivity against mitogens and antilymphocyte antibody to yield the following results : 1) Total lymphocyte counts in the peripheral blood and the absolute T cell number decreased after irradiation, although no changes were found in T cell percentage. 2) In order to evaluate immune response in uterine cancer patients undergoing therapeutic irradiation, in vitro lymphocyte transformation tests using PHA, Con A, PWM and PPD, as well as mensuration of IgG, IGA, IgM, C3, and C4, were carried out on the blood obtained from each patient before and during therapy : During irradiation, the lymphocyte transformation values against PHA and Con A were depressed, but no significant changes were found in the values of IgG, IgA, and IgM. In some patients, however, the IgG, IgM, C3 and C4 values were slightly increased after irradiation. 3) Using sera with high anti-lymphocyte antibody titers obtained from SLE patients, a cyto toxicity test against normal lymphocytes and lymphocytes from Co60 -treated patients was carried out : In approptiate seral dilution, less cytotoxicity was found in lymphocytes obtained from Co60 treated patients than in those obtained from normal patients lymphocytes, i.e. lymphocytes from Co60 treated patents were found to be more resistant to the cytotoxic sera than normal lymphocytes. (author)

  2. Production of point defects

    Vacancies at thermodynamic equilibrium and the annealing of these defects are studied first, after which electron irradiations are dealt with. The displacement threshold energy concept is introduced. Part three concerns heavy ion and neutron irradiations. Displacement cascades and the thermal spike concept are discussed

  3. Quantum computing with defects.

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


    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. PMID:20404195

  4. Topological defects in CFT

    Petkova, V. B., E-mail: [Bulgarian Academy of Sciences, Institute of Nuclear Research and Nuclear Energy (Bulgaria)


    Areview of the notion, properties and the use of topological defects in 2d conformal field theories is presented. An emphasis is made on the recent interpretation of such operators in non-rational theories, as describing Wilson-'t Hooft loop operators of N = 2 supersymmetric 4d topological theories.

  5. Lymphocytic subsets and low-dose exposure

    The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

  6. Lymphocyte transformation in presumed ocular histoplasmosis

    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

  7. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

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


    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.

  8. Ibrutinib (PCI-32765) in Chronic Lymphocytic Leukemia

    Jain, Nitin; O’Brien, Susan


    B-cell receptor (BCR) signaling is essential for chronic lymphocytic leukemia (CLL) cell survival. Many kinases in the BCR signaling pathway are currently being studied as potential therapeutic targets. These include Lyn, Syk, PI3 and Bruton tyrosine (BTK). Ibrutinib (PCI-32765) is a novel first-in-class selective inhibitor of BTK. Preclinical evidence suggests that ibrutinib inhibits CLL cell survival and proliferation. In addition, it also affects CLL cell migration and homing. Early clinic...

  9. Lymphocyte subpopulations in mammary cancer after radiotherapy

    B- and T-lymphocytes, identified by two methods of rosette-formation with sheep erythrocytes, fall to low levels within 1 week of the start of post-operative radiotherapy for cancer of the breast. Fifty-two such patients are compared with 34 age- and disease-matched patients treated by mastectomy alone. The B-lymphopenia reverts to normal levels by 10 months while the T-lymphopenia persists for at least 2 to 4 years

  10. Defect identification by compositional defect review using auger electron spectroscopy

    Defect identification plays an enabling role in determining the source of particles that occur during semiconductor processing and are subsequently detected by defect inspection tools. Auger electron spectroscopy provides a high spatial resolution, surface sensitive analytical probe that is well matched to examining small, thin or complex defects. A focused ion beam (FIB) can be used to cross-section buried defects and structures for subsequent Auger analysis. Such measurements have been made on defects from two wafers pulled at different process steps. One wafer was analyzed after poly-Si deposition, and the other wafer was analyzed after metal 2 etch. The defects on the poly-Si wafer are Si particles. Three types of particles were found on the metal 2 wafer: C-based, stainless steel, and Si-oxide. The majority of defects on this wafer are C-based. Auger, EDS and FIB results will be compared for representative defects on these two wafers

  11. Essential role of Elmo1 in Dock2-dependent lymphocyte migration.

    Stevenson, Catherine; de la Rosa, Gonzalo; Anderson, Christopher S; Murphy, Patrick S; Capece, Tara; Kim, Minsoo; Elliott, Michael R


    Elmo1 and Elmo2 are highly homologous cytoplasmic adaptor proteins that interact with Dock family guanine nucleotide exchange factors to promote activation of the small GTPase Rac. In T lymphocytes, Dock2 is essential for CCR7- and CXCR4-dependent Rac activation and chemotaxis, but the role of Elmo proteins in regulating Dock2 function in primary T cells is not known. In this article, we show that endogenous Elmo1, but not Elmo2, interacts constitutively with Dock2 in mouse and human primary T cells. CD4(+) T cells from Elmo1(-/-) mice were profoundly impaired in polarization, Rac activation, and chemotaxis in response to CCR7 and CXCR4 stimulation. Transfection of full-length Elmo1, but not Elmo2 or a Dock2-binding mutant of Elmo1, rescued defective migration of Elmo1(-/-) T cells. Interestingly, Dock2 protein levels were reduced by 4-fold in Elmo1(-/-) lymphocytes despite normal levels of Dock2 mRNA. Dock2 polyubiquitination was increased in Elmo1(-/-) T cells, and treatment with proteasome inhibitors partially restored Dock2 levels in Elmo1(-/-) T cells. Finally, we show that Dock2 is directly ubiquitinated in CD4(+) T cells and that Elmo1 expression in heterologous cells inhibits ubiquitination of Dock2. Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes. Inhibition of Dock2 has therapeutic potential as a means to control recruitment of pathogenic lymphocytes in diseased tissues. This work provides valuable insights into the molecular regulation of Dock2 by Elmo1 that can be used to design improved inhibitors that target the Elmo-Dock-Rac signaling complex. PMID:24821968

  12. Apoptosis signaling pathways and lymphocyte homeostasis

    Guangwu Xu; Yufang Shi


    It has been almost three decades since the term "apoptosis" was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways of apoptotic cell death induction: extrinsic signaling through death receptors that leads to the formation of the death-inducing signaling complex (DISC), and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.

  13. Microgravity and Cellular Consequences in Lymphocyte Function

    Pellis, Neal R.; Sundaresan, Alamelu


    Mammalian cells adapt to the environment of low gravity and express a series of responses, some possibly from direct effects on cells and others based on environmental conditions created by microgravity. Human lymphocytes in microgravity culture are functionally diminished in activation and locomotion. Both processes are integral to optimal immune response to fight pathogens. The NASA Rotating-wall vessel (RWV) is a well-accepted analog for microgravity culture on the ground. Gene array experiments and immunoblotting identified upstream events in human lymphocytes adapting to microgravity analog culture. Microgravity induces selective changes, many of which are cell membrane related. Results showed that upstream of PKC in the T cell activation cascade, PLC-gamma and LAT are significantly diminished. ZAP 70 which controls LAT activation is also down regulated in modeled microgravity. Thus events governing cell shape might warrant attention in microgravity conditions. The goal of this study is to delineate response suites that are consequential, direct or indirect effects of the microgravity environment and which of these are essential to lymphocytes

  14. Introduction of micronuclei in human irradiated lymphocytes

    The appearance of micronuclei (MN) was induced in human blood lymphocytes to establish the existence of a dose-response relationship between radiation and micronucleus frequency and determine the lowest radiation dose that can be valued by the micronucleus assay. To do so, two different types of experiment were conducted: a) induction of micronuclei in human lymphocytes by gamma radiation ''in vitro''; b) induction of micronuclei in human lymphocytes whit low doses of X-rays ''in vitro''. Statistically, a linear-quadratic dependency relationship was found (y=K+alpha.D-Beta.D''2) between the number of micronuclei and the doses of radiation administered. The lowest dose that can be value by the micronucleus assay could be established as 4-16 cGy depending on the criteria used for determination. The micronucleus assay is a useful and simple test to determine the dose-response relationship, thus enabling it to be applied as a biological dosimeter in situations where physical dosimetry is not possible or is absent. (Author) 35 refs

  15. Normal lymphocyte immunophenotype in an elderly population

    Sâmia Macedo Queiroz Mota Castellão Tavares


    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.

  16. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

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


    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.

  17. Effect of sublethal ionizing radiation on rat Peyer's patch lymphocytes

    After sublethal doses of ionizing radiation, rat Peyer's patch lymphocytes regenerated significantly more slowly than lymphocytes from spleen, thymus, and peripheral lymph nodes. Long Evans rats were exposed to 150 rad of whole-body irradiation from a 60Co, γ-emitting source. On Days 1-20 postirradiation, single cell suspensions of lymphocytes from thymus, spleen, peripheral lymph nodes, and Peyer's patches were stained with mouse monoclonal antibody reagents specific for rat lymphocyte subpopulations. Cells were then counterstained with Texas Red-conjugated, goat antimouse IgG and, at the same time, were also stained with fluorescein diacetate to determine viable lymphocytes. The stained lymphocytes were analyzed using a dual-laser, fluorescent-activated cell sorter from which the percentage of each lymphocyte subpopulation was determined. The authors observed that viable lymphocyte subpopulation in thymus, spleen, and peripheral lymph nodes from irradiated animals returned to normal (nonirradiated control animals) levels 5-12 days postirradiation, while viable lymphocyte subpopulations in Peyer's patches from irradiated animals remained suppressed up to 20 days postirradiation. These results suggest that either the lymphocytes or, more likely, the microenvironment of Peyer's patches is more greatly damaged by ionizing radiation than that observed in other lymphoid tissue

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

    Barrientos, Jacqueline C


    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. PMID:27324214

  19. Birth Defects Research and Tracking

    ... Podcasts & Video E-Cards Flu Badge Real Stories Cleft Lip and Palate Craniosynostosis Down Syndrome Eye Defects Fetal Alcohol Syndrome ... premature birth, certain birth defects (such as cleft lip, cleft palate, or both ), and infant death. Quitting smoking before ...

  20. Impact of Congenital Heart Defects

    ... High Blood Pressure Tools & Resources Stroke More The Impact of Congenital Heart Defects Updated:Oct 21,2015 ... is an important part of successful coping. The Impact of Congenital Heart Defects • Home • About Congenital Heart ...

  1. Atrial Septal Defect (For Parents)

    ... Video) Going to the Hospital Your Heart & Circulatory System Quiz: Heart & Circulatory System EKG (Video) What's It Like to Have Surgery? Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Anesthesia Basics Contact Us Print Resources Send to ...

  2. Common Types of Heart Defects

    ... heart –body. More information about Single Ventricle Defects . Tetralogy of Fallot What is it? A heart defect that features ... right chamber becomes overly thickened More information about Tetralogy of Fallot . Total Anomalous Pulmonary Venous Connection (TAPVC) What is ...

  3. Point defects in silicates

    Topaz is a wide band gap insulating crystal with four Al2F2SiO4 formula units per orthorhombic unit cell and containing isolated SiO4 tetrahedron. Electron spin resonance (ESR), UV-VIS spectrophotometry, photoluminescence, and isochronal annealing were used to study the point defects introduced by fast-neutron bombardment or by alpha decay recoils. The superoxide radical is characterized by a single hole-like spin 1/2 signal with principle g-values gxx = 2.0055, gzz = 2.0407 and the major axis of the defect points along 0.356a + 0.152b + 0.922c. The superoxide anneals near 650C. Two polarization dependent absorptions occur in the UV due to the transitions 2IIg → 2IIu and 2IIg → 2Δu. The former has an oscillator strength of 0.06. The 2.5 eV polarization dependent luminescence is due to the transition 2IIg → 2IIu. The 2Δu → 2IIu is non-radiative. The doubly occupied dangling silicon bond, the blue center, is characterized by a 2 eV polarization dependent absorption and is non-paramagnetic. The transition dipole for this absorption points in the direction 0.93a + 0.210b + 0.305c and the oscillator strength is approximately 2.0 x 10-3. The blue center anneals at 500C. This dangling bond defect is one of two models proposed for a similar 2 eV absorption in silica glass. The defects in quartz (SiO2) were introduced by the recoil nuclei after alpha decays of uranium, thorium, and their daughters in natural abundances. The accumulating damage provides a geological clock by which the age of the quartz can be found. The sample came from Yucca Flats, Nevada, the proposed site of a nuclear waste dump

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

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


    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.

  5. Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics

    Thangada, Shobha; Khanna, Kamal M.; Blaho, Victoria A.; Oo, Myat Lin; Im, Dong-Soon; Guo, Caiying; Lefrancois, Leo; Hla, Timothy


    The sphingosine 1-phosphate receptor 1 (S1P1) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein–coupled receptor correlates with inhibition of lymphocyte egress and results in lymphopenia. However, it is unclear if S1P1 internalization is necessary for this effect. We characterize a knockin mouse (S1p1rS5A/S5A ) in which the C-terminal serine-rich S1P1 motif, which is important for S1P1 internalization but dispensable ...

  6. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Griffin, G.D.; Schuresko, D.D.


    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  7. Benign gastric filling defect

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  8. Specific receptor binding of staphylococcal enterotoxins by murine splenic lymphocytes.

    Buxser, S; Bonventre, P F; Archer, D L


    We describe a reliable assay to measure the specific binding of 125I-labeled staphylococcal enterotoxin A (SEA) by murine spleen cells. Toxin binding by lymphocytes was specific in that it was inhibited by unlabeled SEA but not by unrelated proteins. The biological activity of SEA (T-lymphocyte mitogenesis) correlated with toxin binding to splenic lymphocytes. In the presence of high concentrations of [125I]SEA, specific binding increased rapidly and approached saturation after 2 h. Toxin bin...

  9. Peripheral blood and mesenteric lymph node lymphocytes in Crohn's disease.

    Richens, E R; Thorp, C M; Bland, P W; Gough, K R


    Analysis of peripheral blood lymphocytes from 44 patients with Crohn's disease showed no difference in the proportions of T- and B-cells from those in 38 healthy controls. Analysis revealed no disturbances in relation to duration or to activity of disease or to drug treatment. Lymphocytes from 18 patients with rheumatoid arthritis also showed normal proportions of T- and B-cells. Lymphocytes taken from gut lymph nodes were studied in five patients with Crohn's disease. On comparison with peri...

  10. Antisite defects at oxide interfaces

    Chen, Hanghui; Millis, Andrew


    We use ab initio calculations to estimate the formation energies of cation (transition-metal) antisite defects at oxide interfaces and to understand the basic physical effects that drive or suppress the formation of these defects. Antisite defects are found to be favored in systems with substantial charge transfer across the interface, while Jahn-Teller distortions and itinerant ferromagnetism can prevent antisite defects and help stabilize atomically sharp interfaces. Our results enable identification of classes of systems that may be more and less susceptible to the formation of antisite defects, and they motivate experimental studies and further theoretical calculations to elucidate the local structure and stability of oxide interface systems.

  11. Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene

    An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients

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

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard; Ørding Andreasen, Susanne; Röpke, C; Marker, O; Thomsen, Allan Randrup


    -specific TCR are adoptively transferred before virus challenge, indicating that the disease is the result of an unfortunate balance between virus replication in internal organs, e.g., liver and spleen, and the host response; resetting this balance by increasing host responsiveness will again lead to a rapidly......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...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

  13. Phenotypic and Functional Analysis of Porcine T Lymphocytes

    李华; 陈应华


    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.

  14. Activation of B lymphocytes by mycoplasma mitogen(s)

    Various strains of the murine mycoplasma M.neurolyticum have been shown to induce extensive blast transformation of mouse lymphocytes, comparable in strength to mitogenicity exerted by these mycoplasma species on rat lymphocytes. The data demonstrate that this mitogenic effect is non-specific. Lymphoid cells from mycoplasma free, germ-free mice were activated to the same extent as those lymphocytes obtained from conventionally bred animals. Lymph node cell suspensions obtained from athymic nude mice were strongly activated by M.neurolyticum mitogen. Furthermore, mouse thymocytes and mouse T-cell enriched populations, were not stimulted by these mitogens. It was thus suggested that M.neurolyticum activates mouse B lymphocytes. (author)

  15. Relation of age to lymphocyte radiosensitivity in vitro

    Lymphocytes from one-year old children were significantly more sensitive to in vitro X-irradiation than those from adults as measured by Con-A-stimulated tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST). No significant difference in the radiosensitivity of the PHA response was observed between the two groups in either the LST or colony formation assay. The increased radiosensitivity and poor colony formation of Con-A-responding lymphocytes from the one-year old children may reflect differences in functional maturational differentiation of lymphocyte subpopulations as compared to those of the adult population

  16. Defect disorder in UO2

    A defect disorder model has been developed to determine equilibrium off-stoichiometry and its spatial variations in UO2 crystals. The model gives the concentrations of atomic defects and electronic carriers as functions of oxygen partial pressure and temperature in the bulk and near crystal surfaces subject to an oxygen environment. Energetic parameters from published density functional theory calculations have been integrated into the defect disorder model for an accurate determination of the defect density and off-stoichiometry. The ionosorption theory has been used to couple the oxygen environment with the defect state in the crystal as we solved for the defect disorder near crystal surfaces. Contrary to the common belief that hyper-stoichiometry of UO2 is dominated by oxygen interstitials, the current model predicts that this regime is rather dominated by uranium vacancies. The model predictions also show that, in the presence of surfaces, the point defect concentrations vary by orders of magnitude in the subsurface region relative to the bulk region. Highlights: • Defect disorder in bulk UO2+x is modeled in terms of temperature and oxygen pressure. • The densities of atomic defects and electronic charge carriers are determined. • The model is extended to study the heterogeneity of defect density near crystal surfaces. • The surface effect is modeled using ionosorption theory. • The dominant defect type and off-stoichiometry profile near surface are found

  17. Invisible defects in complex crystals

    We show that invisible localized defects, i.e. defects that cannot be detected by an outside observer, can be realized in a crystal with an engineered imaginary potential at the defect site. The invisible defects are synthesized by means of supersymmetric (Darboux) transformations of an ordinary crystal using band-edge wavefunctions to construct the superpotential. The complex crystal has an entire real-valued energy spectrum and Bragg scattering is not influenced by the defects. An example of complex crystal synthesis is presented for the Mathieu potential. -- Highlights: •We show the existence of invisible localized defects in complex crystals. •They turn out to be fully invisible to Bloch waves belonging to any lattice band. •An example of invisible defect is presented for a PT-symmetric Mathieu crystal

  18. Fungal natural products targeting chronic lymphocytic leukemia

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen;


    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....../compounds.2,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia...

  19. Analysis in cytokinesis-blocked human lymphocytes

    Biological dosimetry can be considered as an additional method to physical dosimetry for estimating dose absorption after exposure to ionizing radiation. Fully validated as well as new promising approaches in this field are reviewed. Recent experiments, carried out in our laboratory, on the analysis of micronuclei in cytokinesis-blocked human lymphocytes are presented. The possible relevance of differential human individual response to ionizing radiation, in view of the occurrence of radiosensitive syndromes, for the estimation of the absorbed dose in human is also discussed

  20. DNA repair in PHA stimulated human lymphocytes

    Damage an repair of radiation induced DNA strand breaks were measured by alkaline lysis and hydroxyapatite chromatography. PHA stimulated human lymphocytes show that the rejoining process is complete within the first 50 min., afterwords secondary DNA damage and chromatid aberration. DNA repair, in synchronized culture, allows to evaluate individual repair capacity and this in turn can contribute to the discovery of individual who, although they do not demonstrate apparent clinical signs, are carriers of DNA repair deficiency. Being evident that a correlation exists between DNA repair capacity and carcinogenesis, the possibility of evaluating the existent relationship between DNA repair and survival in tumor cells comes therefore into discussion

  1. Casein expression in cytotoxic T lymphocytes.

    Grusby, M J; Mitchell, S C; Nabavi, N; Glimcher, L H


    A cDNA that expresses a mRNA restricted to cytotoxic T lymphocytes (CTL) and mammary tissue has been isolated and characterized. The deduced amino acid sequence from this cDNA shows extensive homology with the previously reported amino acid sequence for rat alpha-casein. Indeed, the presence of a six-residue-repeated motif that is specific for rodent alpha-caseins strongly supports the identification of this cDNA as mouse alpha-casein. Northern (RNA) blot analysis of many hematopoietic cell t...

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

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


    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...

  3. Point defects in nickel

    The defects in electron irradiated nickel (20 deg. K) or neutron irradiated nickel (28 deg. K) are studied by simultaneous analysis using the magnetic after-effect, electron microscopy and electrical resistivity recovery. We use zone refined nickel (99.999 per cent) which, for some experiments, is alloyed with a small amount of iron (for example 0.1 per cent Fe). The temperature dependant electrical recovery may be divided in four stages. The sub-stages IB (31 deg. K), IC (42 deg. K), ID (from to 57 deg. K) and IE (62 deg. K) of stage I are due to the disappearance of single interstitials into vacancies. The interstitial defect has a split configuration with a migration energy of about 0.15 eV. In the close pair which disappears in stage IB the interstitial is found to be in a 3. neighbour position whilst in stage ID it is near the direction from the vacancy. In stage IE there is no longer any interaction between the interstitial and the vacancy. The stage II is due to more complicated interstitial defects: di-interstitials for stage IIB (84 deg. K) and larger and larger interstitial loops for the following sub-stages. The loops may be seen by electron microscopy. Impurities can play the role of nucleation centers for the loops. Stages IIIA (370 deg. K) and IIIB (376 deg. K) are due to two types of di-vacancies. During stage IV (410 deg. K) the single vacancies migrate. Vacancy type loops and interstitial type loops grow concurrently and disappear at about 800 deg. K as observed by electron microscopy. (author)

  4. Topological defect lasers

    Knitter, Sebastian; Xiong, Wen; Guy, Mikhael I; Solomon, Glenn S; Cao, Hui


    We demonstrate topological defect lasers in a GaAs membrane with embedded InAs quantum dots. By introducing a disclination to a square-lattice of elliptical air holes, we obtain spatially confined optical resonances with high quality factor. Such resonances support powerflow vortices, and lase upon optical excitation of quantum dots, embedded in the structure. The spatially inhomogeneous variation of the unit cell orientation adds another dimension to the control of a lasing mode, enabling the manipulation of its field pattern and energy flow landscape.

  5. Single ventricle cardiac defect

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  6. 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

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


    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) and...

  7. Thymic lymphocyte differentiation and thymic leukemogenesis

    Henry Kaplan helped establish the fields of lymphocyte biology and viral leukemogenesis by his early and continuing studies on radiation leukemogenesis. As one of Henry's students I carried on these dual preoccupations with thymic lymphocytopoiesis and thymic lymphomagenesis. This communication demonstrates that 1) thymic lymphoctyes are derived from bone marrow precursors which lack any T cell markers; 2) these bone marrow cells (or their clonogenic subsets) can give rise to either thymic cortical plus medullary progeny, or medullary progeny alone; 3) thymic lymphocytes mature in contract with 3-5 classes of monlymphoid cells and one of these subsets, cortical dendritic epithelial cells, express an unusual distribution of MHC antigen; 4) the population of cells which are poised to emigrate from the thymus are a unique subset of cortical cells which possess peripheral lymphoid organ homing receptors; and 5) the thymic target cells for retrovirus lymphomagenesis express highly specific retrovirus receptors that are analogous (and perhaps synonymous) with antigen-specific T cell receptors

  8. [Congenital defects and incapacity].

    Jouve de la Barreda, Nicolás


    As a whole the congenital defects constitute an important section of the medical attention affecting near 3% of the population. A 15% of spontaneous abortions take place of which the greater frequency corresponds to the chromosome anomalies (25%) and the monogenic mutations (20%) and in a lesser extent to the effects of teratogenic agents. Between the genetic causes determining the congenital defects the mutations that affect genes acting in the early stages of development occupy a main place. These alterations can affect to homeotic genes or monogenic systems that act during the critical phases of the organogenesis. It seems evident that an alteration in the expression of a necessary gene for the appearance of a morphogenetic change constitutes the angular stone to understand resurging of a malformation or discapacity. In the last years has been demonstrated the importance of the teratogenic or environmental agents on the delicate internal physiological balance during the critical stages of the development. In this context must be included the inductive environmental factors inducing epigenetic modifications in the early stage of the development of the embryos produced by fertilization in vitro. PMID:19799481

  9. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia


    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  10. Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection

    Han, Song Yi; Lee, I Re; Park, Se Jin; Kim, Ji Hong


    Purpose Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). Methods We retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. Results WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). Conclusion NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction.

  11. The behavior of pig lymphocyte populations in vivo

    Lymphocyte migration provides the means of rapidly recognizing and responding to antigen and widely disseminating the resulting immune response. The porcine lymphoid system differs from that of man in structural inversion of lymph nodes and route of lymphocyte recirculation and the existence of two Peyer's patch types, one of which differs from the conventional pattern in structure, cell content and lack of lymphocyte traffic and in its regression in old age. Recirculating T and B lymphocytes enter and leave spleen and lymph nodes by the blood but Null cells do not; lymphocytes also migrate through nonlymphoid tissues. The lung is one such important site, with a small migration in and out of alveolar space and a large traffic associated with the blood vessel wall, predominantly involving T cells. Blood lymphocytes hardly traffic into the peritoneal cavity, yet major traffic of particulate material or cells is possible in this important site of abdominal defense, so often used for immunization, and follows a distinct, well defined route. Cells migrate out of subcutaneous tissue via the draining node. Lymphocytes are produced and emigrate into blood from labelled thymus. They differ in size and surface phenotype from both thymocytes and peripheral T cells. Lymphocytes also migrate from blood into most tissues. In most nonlymphoid tissues, entry relates to blood flow but in many lymphoid tissues it is an active process which differs in tempo and extent, eg, between different nodes and between the two Peyer's patch types

  12. The molecular basis of familial chronic lymphocytic leukemia

    Crowther-Swanepoel, Dalemari; Houlston, Richard S.


    Our understanding of the genetic basis of chronic lymphocytic leukemia is only just starting to be recognized. This perspective article by Drs. Crowther-Swanepoel and Houlston provides an up-to-date review the molecular epidemiology of chronic lymphocytic leukemia, with emphasis on the integration of biology and genomics. See related paper on page 647.

  13. Role of interferon in lymphocyte recruitment into the skin

    Large numbers of lymphocytes are recruited from the blood into sites of cutaneous DTH reactions. Our goal was to investigate the factors controlling this recruitment. 111In-labeled peritoneal exudate lymphocytes were injected iv and the accumulation of these cells in skin sites injected with a variety of stimuli, was used to measure lymphocyte recruitment in rats. Large numbers of lymphocytes migrated into vaccinia- and KLH-injected sites in sensitized animals, but only into the viral and not the KLH lesions in non-immune animals. Lymphocytes also migrated efficiently into sites injected with the alpha-interferon (IFN) inducers, uv-inactivated vaccinia virus and poly I:C, as well as into sites injected with IFN. In each case there was a dose-response relationship. Analysis of the kinetics of lymphocyte recruitment demonstrated that the peak rate of migration occurred most rapidly after the injection of IFN, later after poly I:C, and was slowest to be reached after vaccinia virus. Rabbit anti-IFN blocked the recruitment of lymphocytes by uv-inactivated vaccinia and by IFN. Histologically, all of these sites demonstrated a dense mononuclear cell infiltrate in the dermis. It is suggested that IFN may be an important mediator in the recruitment of lymphocytes into inflammatory reactions

  14. T-lymphocyte subsets in recurrent aphthous ulceration

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


    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...

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

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


    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. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    Hadrup, Sine Reker


    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...... recognition of the majority of the CD8 tumor infiltrating lymphocytes remains to be identified....

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

    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...

  18. [Fractionation of lymphocytes using affinity chromatography with 9 lectins].

    de Dios, I; Manso, M; López-Borrasca, A


    Lymphocyte subclasses from normal peripheral blood have been fractionated by affinity chromatography with lectins. Concanavalin A (Con A), Lens culinaris lectin (LC), Pisum sativum lectin (PS), Phaseolus vulgaris lectin (PHA), Dolichos biflours lectin (DB), Glicine max lectin (SBA), Ricinus communis lectin (RCA II), Tetragonolobus purpureus lectin (TP) and Triticum vulgaris lectin (WGA), were coupled to Sepharose 6MB, and lymphocytes labelled with 125I were eluted through the chromatographic columns. The binding of lymphocytes to WGA and SBA lectins was 32% and 13% respectively. The binding to the other lectins tested were found to be between 32% and 13%. When solutions of increasing concentrations of specific sugar were added to the columns a progressive elution of bound lymphocytes was observed. These results indicate the existence of a large range of lymphocyte subclasses, with different binding capacity to lectins, which was a function of the receptor number or/and receptor affinity to each lectin. Furthermore, these two parameters were found to vary in each functional population. Even though all the lymphocytes had lectin receptors, T lymphocytes showed higher affinity for Con A, PHA and TP lectins, while B lymphocytes appeared to be more specific for LC, PS, SBA, DB, RCAII and WGA lectins. PMID:6675094

  19. Lymphocytes as a neural probe : potential for studying psychiatric disorders

    Gladkevich, A; Kauffman, HF; Korf, J


    There is an increasing body evidence pointing to a close integration between the central nervous system (CNS) and immunological functions with lymphocytes playing therein a central role. The authors provide arguments to consider blood lymphocytes as a convenient probe of-an albeit-limited number of

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

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


    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. Unex...

  1. Lymphocytes in patients with psoriasis promote proliferation of keratinocytes

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


    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.

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

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


    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.

  3. Lymphocyte respiration in children with Trisomy 21

    Aburawi Elhadi H


    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.

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

    Eldrup, Morten Mostgaard; Singh, B.N.


    A brief introduction to positron annihilation spectroscopy (PAS), and in particular lo its use for defect studies in metals is given. Positrons injected into a metal may become trapped in defects such as vacancies, vacancy clusters, voids, bubbles and dislocations and subsequently annihilate from...... advantages of the use of PAS are pointed out. (C) 1997 Elsevier Science B.V....

  5. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  6. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Giovanni D'Arena


    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.

  7. [The genetic landscape of chronic lymphocytic leukemia].

    Marosvári, Dóra; Alpár, Donát; Király, Attila Péter; Rajnai, Hajnalka; Reiniger, Lilla; Bödör, Csaba


    Chronic lymphocytic leukemia (CLL) is the most frequent mature B-cell non-Hodgkin's lymphoma in the Western countries. The recent next-generation sequencing (NGS) studies lead to an exponential increase in our knowledge of the pathogenesis and progression of CLL. Whole genome and exome sequencing studies revealed a remarkable inter- and intra-patient genetic heterogeneity with a significant therapy-induced clonal evolution in the majority of the patients. Driver mutations were identified in components of various signalling pathways and cellular processes with notable prognostic and therapeutic relevance. Interestingly, these studies revealed only a few genes mutated in at least 15-20% of the patients with a larger number of genes mutated in a smaller proportion of patients. This improved understanding of the genomic landscape of CLL has opened new avenues for a more precise patient stratification and rational application of novel, more effective targeted therapies. PMID:27275638

  8. Initial therapy of chronic lymphocytic leukemia.

    Eichhorst, Barbara; Cramer, Paula; Hallek, Michael


    Only chronic lymphocytic leukemia (CLL) patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. Prognostic risk factor profile and comorbidity burden are most relevant for the choice of treatment. For physically fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) plus milder chemotherapy (chlorambucil) may be applied. Patients with a del(17p) or TP53 mutation should be treated with the kinase inhibitors ibrutinib or a combination of idelalisib and rituximab. Clinical trials over the next several years will determine, whether kinase inhibitors, other small molecules, immunotherapeutics, or combinations thereof will further improve outcomes for patients with CLL. PMID:27040702

  9. Predictive radiosensitivity tests in human lymphocytes

    Individual radiosensitivity is an inherent characteristic, associated with an abnormally increased reaction to ionising radiation of both the whole body and cells derived from body tissues. Human population is not uniform in its radiation sensitivity. Radiosensitive sub-groups exist, which would suffer an increased incidence of both deterministic and stochastic effects. Clinical studies have suggested that a large part of the spectrum of normal tissue reaction may be due to differences in individual radiosensitivity. The identification of such sub-groups should be relevant for radiation therapy and radiation protection purposes. It is suggested that DNA repair mechanisms are involved. Consequently, the characterization of DNA repair in lymphocytes through cytokinesis blocked micronucleus (MN) and alkaline single-cell microgel electrophoresis (comet) assays could be a suitable approache to evaluate individual radiosensitivity in vitro. The aims of this study were: 1) To assess the in vitro radiosensitivity of peripheral blood lymphocytes from two groups of cancer patients (prospectively and retrospectively studied), using MN and comet assays, in comparison with the clinical radiation reaction and 2) To test the predictive potential of both techniques for the identification of radiosensitivity sub-groups. 38 cancer patients receiving radiation therapy were enrolled in this study. 19 patients were evaluated prior, mid-way and on completion of treatment (prospective group) and 19 patients were evaluated about 6-18 month after radiotherapy (retrospective group). Cytogenetic data from the prospective group were analysed using a mathematical model to evaluate the attenuation of the cytogenetic effect as a function of the time between a single exposure and blood sampling, estimating a cytogenetic recovery factor k. In the retrospective group, blood samples were irradiated in vitro with 0 (control) or 2 Gy and evaluated using MN test. Cytogenetic data were analysed

  10. Fungal natural products targeting chronic lymphocytic leukemia

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen; Gotfredsen, Charlotte Held; Duerr, C.; Seiffert, M.; Larsen, Thomas Ostenfeld


    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...... with potential tumor specificity. Our starting point is a diverse fungal collection of thousands of Penicillium and Aspergillus species. These fungi have proven to be a very rich source of various bioactive compounds and yet our dereplication investigations have demonstrated that there are still...... numerous unknown compounds to be identified within these species. Until now we have found that 11 out of 289 fungal extracts are active against CLL cells. Using our established chemotaxonomic discovery approach we have dereplicated and fractionated these extracts to track the activity into single fractions/compounds...

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

    Rebecca J Critchley-Thorne


    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

  12. Irradiation Defects in Silicon Crystal


    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.

  13. Effect of postirradiation anoxia on radiosensitivity of lymphocytes

    Radiosensitivity was measured by viable-lymphocyte counts and by uridine uptake. The viability of the lymphocytes was based on morphologic characteristics visualized by phase contrast microscopy of the cells in a special slide chamber. Low doses of x rays (10 to 1000 R) and incubation at 370C killed lymphocytes in interphase with the production of pyknotic nuclei (nuclear death), and large doses (6000 R) produced nuclei with clear nucleoplasm (cytoplasmic death). Nuclear, but not cytoplasmic, death was inhibited by incubation of the irradiated cells at 270C. Postirradiation anoxia had no effect on development of the nuclear and cytoplasmic death of lymphocytes irradiated with 100 to 6000 R. Anoxia had no effect on the early response of lymphocytes to phytohemagglutinin (PHA) [increase in ribonucleic acid (RNA) and protein synthesis] but inhibited completely the late effects [increase in deoxyribonucleic acid (DNA) synthesis and transformation into lymphoblastoid cells]. The PHA caused relative radioresistance of lymphocytes under aerobic conditions and, to a lesser extent, under anaerobic conditions. The slight radioresistance induced by PHA in anoxic lymphocytes apparently did not depend on an increase in DNA synthesis or on the transformation to lymphoblastoid cells

  14. Global topological k-defects

    Babichev, E


    We consider global topological defects in symmetry breaking models with a non-canonical kinetic term. Apart from a mass parameter entering the potential, one additional dimensional parameter arises in such models -- a ``kinetic'' mass. The properties of defects in these models are quite different from ``standard'' global domain walls, vortices and monopoles, if their kinetic mass scale is smaller than their symmetry breaking scale. In particular, depending on the concrete form of the kinetic term, the typical size of such a defect can be either much larger or much smaller than the size of a standard defect with the same potential term. The characteristic mass of a non-standard defect, which might have been formed during a phase transition in the early universe, depends on both the temperature of a phase transition and the kinetic mass.

  15. Holographic Chern-Simons defects

    Fujita, Mitsutoshi; Melby-Thompson, Charles M.; Meyer, René; Sugimoto, Shigeki


    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 2-dimensional QCD.

  16. Holographic Chern-Simons Defects

    Fujita, Mitsutoshi; Meyer, Rene; Sugimoto, Shigeki


    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.

  17. Changes induced by ultraviolet light in the superhelical DNA of lymphocytes from subjects with xeroderma pigmentosum and normal controls

    Patients with the light-sensitive disease xeroderma pigmentosum (XP) are genetically heterogeneous. Most patients are defective in the excision repair of u.v.-induced DNA damage while some, the XP-variants, seem proficient in excision repair but replicate u.v.-damaged DNA with difficulty. The former have so far been assigned to 5 complementation groups (A to E) of which B and E are extremely rare. Information on the nature of the defect in XP is contradictory. Studies based on the sedimentation of DNA in alkaline gradients suggest that patients of complementation group A can perform the first step of excision repair ('incision') while others, based on the elution by alkali of the DNA of cells lysed on filters, suggest that they cannot. A study has therefore been made of the repair of DNA damaged by u.v. irradiation using a method based on a precisely defined theoretical approach. Analysis of the sedimentation of nucleoids from normal and XP lymphocytes in sucrose gradients containing different concentrations of ethidium indicated that their DNA is similarly supercoiled. The lymphocyte of patients of complementation groups A, C and D repaired damage induced by γ-rays just like controls. However, they could not repair normally DNA damaged by u.v. irradiation; the cells are defective in the first step of excision repair. The XP-variant and XP-heterozygous cells repaired u.v.- and γ-ray-induced damage like controls. Some problems regarding the nature of the defect in XP are discussed. (author)

  18. Peripheral T-lymphocytes and delayed hypersensitivity in surgically and radiologically treated patients with early stages of larynx-carcinoma

    122 patients with squamous-cell-carcinoma of the larynx (T1-stage) were examined after surgical or radiological treatment. None of these patients showed evidence of tumor recurrence. Peripheral T-lymphocytes and delayed hypersensitivity were studied in all these patients. According to their treatment, the patients were allotted into three groups and compared with a control group, consisting of 20 patients with nonneoplastic head- and neck-disease. The main finding was a significant decrease in the peripheral T-lymphocytes in surgically- or radiologically-treated patients with a squamous-cell-carcinoma of the larynx (T1-stage). This reduction of T-cells must be interpreted as a congenital or acquired defect of the immunocompetent system. In about half of the control cases the DNCB-tests showed no evidence of delayed hypersensitivity. In view of these results and those reported in the literature, the test should be used critically. In contrast to our earlier findings, where patients received radiotherapy over large areas including big vessels, radiation over a smaller, localised area does not lead to a significant depression of peripheral T-lymphocytes. (orig.)

  19. Irradiated autologous T cells restore the in vitro responsiveness of PWM-activated peripheral blood lymphocytes from splenectomized individuals

    The in vitro immunoglobulin (Ig) secrection of pokeweed mitogen (PWM)-activated peripheral blood lymphocytes (PBL) from individuals splenectomized post-trauma was monitored with a protein A plaque-forming cell (PFC) assay. Cultures of unfractionated as well as reconstituted cultures of isolated erythrocyte rosette-forming (E-RFC)-positive (T lymphocytes) and E-RFC-negative (B lymphocytes) cells were established. Using unfractionated cells, the response was substantially reduced or absent, whereas cultures of autologous untreated B and 2000 rads irradited T cells restored the response to normal levels. Normal T cells were not able to stimulate patients' B cells to Ig-secretion and patients' untreated T cells did not induce plaque formation in normal B cells, whereas irradiated patients' T cells induced development of approximately 50% of the response induced by normal irradiated T cells. These results indicate that the immunological defect in splenectomized individuals is not merely restricted to a high level of radiosensitive T cell suppression but also involves an impaired B cell function and T/B cell cooperation. (author)

  20. HIV-mediated immunodepression: in vitro inhibition of T-lymphocyte proliferative response by ultraviolet-inactivated virus

    In order to assess whether the human retrovirus HIV, like other animal retroviruses, is endowed with intrinsic immunosuppressive activity, we studied the effects of noninfectious, uv-irradiated virus on in vitro lymphocyte function. uvHIV preparations inhibited T-cell proliferation to mitogens and alloantigens, as well as mitogen-driven IL-2 production. The inhibitory effect, which was not exerted by uv-irradiated HTLV-I, was apparently not due to a decrease in cell viability and was likely associated with thermoresistant viral component(s). The suppression proved to be selective for T-cell responses, while sparing other lymphocyte functions, such as the B-cell proliferative response to a selective B-cell mitogen. The inhibitory effect of uvHIV was not counteracted by a substantial reduction in the number of monocytes or by indomethacin. Moreover, IL-1 production by monocytes was not affected upon virus incubation. On the other hand, the proliferative response of both CD4+ and CD8+ T-cell clones was inhibited by uvHIV, suggesting that T cells represent the actual target for the inhibitory effect. Although a sizeable decrease in IL-2 production was observed following uvHIV incubation, exogenous IL-2 was not capable of reversing the virus-induced suppression of the proliferation. The possibility that the immunosuppressive activity of noninfectious HIV contributes to the T-cell defect in infected patients by mechanisms other than the cytopathic effect on CD4+ T lymphocytes is discussed

  1. Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

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


    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...

  2. Protein profiles distinguish stable and progressive chronic lymphocytic leukemia.

    Huang, Pauline Y; Mactier, Swetlana; Armacki, Natalie; Giles Best, O; Belov, Larissa; Kaufman, Kimberley L; Pascovici, Dana; Mulligan, Stephen P; Christopherson, Richard I


    Patients with a stable chronic lymphocytic leukemia (CLL) double their blood lymphocyte count in >5 years, but may develop progressive disease with lymphocytes doubling in selected reaction monitoring) using extracts of purified CD19(+) CLL cells from patients (n = 50). Hierarchical clustering of these protein profiles showed two clusters of patients that correlated with progressive and stable CLL, providing signatures that should be useful for triaging patients. Some of the proteins in the progressive cluster have not been linked with CLL, for example, glutamate dehydrogenase 1 and transcription intermediary factor 1-beta. PMID:26422656

  3. State of T-lymphocytes at different stages of anthracosis

    Tlegenova, A.N.; Baimanova, A.M. (Institut Fiziologii i Gigieny Truda AN Kazakhskoi SSR, Karaganda (USSR))


    Recommends analysis of T-rosette formation in blood samples as a method of diagnosing anthracosis in its early stages in coal miners. Tests were performed on a total of 134 miners aged 38-49, with at least 10 years employment in coal mining. Particularly indicative of developing anthracosis was the ratio of theophylline resistant to theophylline sensitive T-lymphocytes, which increased in sufferers in comparison with the control (although the overall number of T-lymphocytes showed little change). When the anthracosis was complicated by chronic bronchitis, this ratio decreased, with an overall fall in numbers of all T-lymphocytes. 7 refs.

  4. Changes in gravity inhibit lymphocyte locomotion through type I collagen

    Pellis, N. R.; Goodwin, T. J.; Risin, D.; McIntyre, B. W.; Pizzini, R. P.; Cooper, D.; Baker, T. L.; Spaulding, G. F.


    Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes

  5. Holographic Experiments on Defects

    Wapler, Matthias C


    Using the AdS/CFT correspondence, we study the anisotropic charge transport properties of both supersymmetric and non-supersymmetric matter fields on (2+1)-dimensional defects coupled to a (3+1)-dimensional ${\\cal N}=4$ SYM "heat bath". We focus on the case of a finite external background magnetic field, finite net charge density and finite mass. At high frequencies, we discover a spectrum of quasiparticle resonances due to the magnetic field and finite density and at small frequencies, we perform a Drude-like expansion around the DC limit. Both of these regimes display many generic features and some features that we attribute to strong coupling, such as a minimum DC conductivity and an unusual behavior of the "cyclotron" and plasmon frequencies, which become related to the resonances found in the conformal case in an earlier paper. We further study the hydrodynamic regime and the relaxation properties, from which the system displays a set of different possible transitions to the collisionless regime. The mas...

  6. Software Defect Detection with Rocus

    Yuan Jiang; Ming Li; Zhi-Hua Zhou


    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.

  7. Serine biosynthesis and transport defects.

    El-Hattab, Ayman W


    l-serine is a non-essential amino acid that is biosynthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, l-serine is a potent neurotrophic factor and a precursor of a number of essential compounds including phosphatidylserine, sphingomyelin, glycine, and d-serine. Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu-Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. A serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, has been recently described in children with neurological manifestations that overlap with those observed in serine biosynthesis defects. l-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs. Herein, we review serine metabolism and transport, the clinical, biochemical, and molecular aspects of serine biosynthesis and transport defects, the mechanisms of these diseases, and the potential role of serine therapy. PMID:27161889


    Rudolf Mišičko


    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.

  9. Dynamic control of defective gap mode through defect location

    Chang, Lei; Wu, Yun; Wang, Weimin; Song, Huimin


    A 1D model is developed for defective gap mode (DGM) with two types of boundary conditions: conducting mesh and conducting sleeve. For a periodically modulated system without defect, the normalized width of spectral gaps equals to the modulation factor, which is consistent with previous studies. For a periodic system with local defects introduced by the boundary conditions, it shows that the conducting-mesh-induced DGM is always well confined by spectral gaps while the conducting-sleeve-induced DGM is not. The defect location can be a useful tool to dynamically control the frequency and spatial periodicity of DGM inside spectral gaps. This controllability can be applied to optical microcavities and waveguides in photonic crystals and the interaction between gap eigenmodes and energetic particles in fusion plasmas.

  10. Self healing of defected graphene

    For electronics applications, defects in graphene are usually undesirable because of their ability to scatter charge carriers, thereby reduce the carrier mobility. It would be extremely useful if the damage can be repaired. In this work, we employ Raman spectroscopy, X-ray photoemission spectroscopy, transmission electron microscopy, and electrical measurements to study defects in graphene introduced by argon plasma bombardment. We have found that majority of these defects can be cured by a simple thermal annealing process. The self-healing is attributed to recombination of mobile carbon adatoms with vacancies. With increasing level of plasma induced damage, the self-healing becomes less effective.

  11. Folic acid and birth defect prevention

    ... of certain birth defects. These include spina bifida, anencephaly, and some heart defects. Experts recommend women who ... Women who have had a baby with a neural tube defect may need a higher dose of folic acid. ...

  12. Reproduction and Survival After Cardiac Defect Repair


    Cardiovascular Diseases; Heart Diseases; Defect, Congenital Heart; Aortic Valve Stenosis; Transposition of Great Vessels; Ductus Arteriosus, Patent; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Down Syndrome; Tetralogy of Fallot; Pulmonic Stenosis; Coarctation of Aorta

  13. The Genotoxicity of Sodium Arsenite in Human Lymphocyte Culture

    Sodium arsenite was tested for its clastogenic effect alone and on isolated lymphocyte culture. The results showed a significant difference in the yield of chromosome aberrations induced with respect to the culture time 48 h. Whole blood culture showed significant increase in gaps and breaks whereas isolated lymphocyte culture showed significant inhibition of cell cycle and 75% of the lymphocytes were in their first cell cycle at 72 hr. Arsenite showed co-mutagenicity with different doses of x-ray delivered immediately or few hours after treatment of the culture with S A. The results suggest that S A is also mutagenic at the dose level used and provide support for the indispensability of whole blood culture for evaluation of the in vivo effect of any suspected mustagen using isolated lymphocytes appear to have problems leading to extensive cell cycle delay

  14. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    ... both ALL and acute myeloid leukemia (AML). Japanese atomic bomb survivors had a greatly increased risk of developing ... cell acute lymphocytic leukemia. Most cases occur in Japan and the Caribbean area. This disease is not ...

  15. Lymphocyte chromosome aberrations in partial-body fractionated radiation therapy

    a relationship between lymphocyte chromosome aberration yields which occur in partial-body fractionated radiation therapy and those yields measured in vitro is derived. These calculations are applied to the case of patients undergoing radiation therapy for mammary carcinoma. (author)

  16. Lymphocyte chromosome aberrations in partial-body fractionated radiation therapy

    Ekstrand, K.E.; Dixon, R.L. (Wake Forest Univ., Winston-Salem, NC (USA))


    a relationship between lymphocyte chromosome aberration yields which occur in partial-body fractionated radiation therapy and those yields measured in vitro is derived. These calculations are applied to the case of patients undergoing radiation therapy for mammary carcinoma.

  17. The nature of the refractive granules in human lymphocytes

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


    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.

  18. Interaction of nanosilver particles with human lymphocyte cells

    Zhornik, Alena; Baranova, Ludmila; Volotovski, Igor; Chizhik, Sergey; Drozd, Elizaveta; Sudas, Margarita; Buu Ngo, Quoc; Chau Nguyen, Hoai; Huynh, Thi Ha; Hien Dao, Trong


    The damaging effects of nanoparticles were hypothesized to be the oxidative stress caused by the formation of reactive oxygen species and initiation of inflammatory reactions. In this context a study on the effects of nanosilver particles on the formation of reactive oxygen species in human lymphocyte culture was carried out. The obtained results showed that fluorescence intensity considerably increased after cells had interacted with nanosilver particles of varying concentrations, indicating the formation of reactive oxygen species and their accumulation in lymphocyte cells. Morphological study of the lymphocyte cells under the effects of nanosilver particles showed that the change in morphology depends on the concentration and size of nanosilver particles: for a size ≤20 nm the lymphocyte cell significantly shrank with pronounced differences in the morphological structure of the cell membrane, but for a size ≥200 nm no change was observed.

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



    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

  20. Lymphocytes and the Adventitial Immune Response in Atherosclerosis

    Campbell, Kirsti A.; Lipinski, Michael J.; Doran, Amanda C.; Skaflen, Marcus D.; Fuster, Valentin; McNamara, Coleen A.


    Though much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue (PVAT). Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature. PMID:22427326

  1. Human lymphocytes response to low gamma-ray doses

    Radiation and non-radiation workers lymphocytes were exposed to a low strength gamma-ray field to determine heat shock protein expression in function of radiation dose. Protein identification was carried out using mAb raised against Hsp25, Hsp60, Hsp70 and Hsp90; from these, only Hsp70 protein was detected before and after lymphocyte irradiation. In all cases, an increasing trend of relative amounts of Hsp70 in function to irradiation time was observed. After 70.5 μGy gamma-ray dose, radiation worker's lymphocytes expressed more Hsp70 protein, than non radiation workers' lymphocytes, indicating a larger tolerance to gamma rays (gammatolerance), due to an adaptation process developed by his labor condition

  2. Response of human lymphocytes to low gamma ray doses

    Radiation and non-radiation workers lymphocytes were exposed to a low strength gamma-ray field to determine heat shock protein expression in function of radiation dose. Protein identification was carried out using mAb raised against Hsp25, Hsp60, Hsp70 and Hsp90; from these, only Hsp70 protein was detected before and after lymphocyte irradiation. In all cases, an increasing trend of relative amounts of Hsp70 in function to irradiation time was observed. After 70.5 mGy gamma-ray dose, radiation worker's lymphocytes expressed more Hsp70 protein, than non-radiation workers' lymphocytes, indicating a larger tolerance to gamma rays (gamma tolerance), due to an adaptation process developed by their labor condition (Au)

  3. Asymmetric Cell Division in T Lymphocyte Fate Diversification.

    Arsenio, Janilyn; Metz, Patrick J; Chang, John T


    Immunological protection against microbial pathogens is dependent on robust generation of functionally diverse T lymphocyte subsets. Upon microbial infection, naïve CD4(+) or CD8(+) T lymphocytes can give rise to effector- and memory-fated progeny that together mediate a potent immune response. Recent advances in single-cell immunological and genomic profiling technologies have helped elucidate early and late diversification mechanisms that enable the generation of heterogeneity from single T lymphocytes. We discuss these findings here and argue that one such mechanism, asymmetric cell division, creates an early divergence in T lymphocyte fates by giving rise to daughter cells with a propensity towards the terminally differentiated effector or self-renewing memory lineages, with cell-intrinsic and -extrinsic cues from the microenvironment driving the final maturation steps. PMID:26474675


    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


    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

  5. The influence of the long term voyage on the lymphocytes of nuclear-powered submarine crews

    Objective: To study the influence of long term voyage on the number and activity of the nuclear-powered submarine crew's lymphocytes. Methods: Before and after long term voyage, the total number lymphocytes of peripheral blood were measured; pured lymphocytes were planted to count the number of T lymphocyte colonies; and the apoptosis rate T lymphocyte was measured. Results: After long term voyage, the total amount of lymphocyte is increased; the T lymphocyte make much more colonies after planting; and the apoptosis rate of T lymphocyte is raised. Conclusion: Long term voyage in nuclear-powered submarine can affect the account of peripheral blood lymphocyte and the activity of T lymphocyte. The cumulative effect of micro-radiation in cabin can affect the immune function of the crew, more protection need to be strengthened to enhance the health. (authors)

  6. Inhibition of lymphocyte activation by gold sodium thiomalate.

    Hopkins, S J; Jayson, M I; Zeil, P.


    Activation of lymphoid cells by both T and B cell mitogens was inhibited by gold sodium thiomalate (GST). The action of GST did not appear to be exerted at early stages of lymphocyte activation. Inhibition by GST was sustained throughout 4 days of culture. The inhibitory effect of GST was reduced at low serum concentrations. Sodium thiomalate and sodium chloroaurate were also able to inhibit lymphocyte activation.

  7. Intraepithelial lymphocytes in the jejunal mucosa of malnourished rats.

    Maffei, H V; Rodrigues, M. A.; de Camargo, J L; Campana, A. O.


    Intraepithelial lymphocytes (IEL) have been counted in the jejunal mucosa of adult Wistar rats submitted to a protein-free diet for 84 days and of a control group receiving a 20% casein diet, in order to evaluate the effect of protein deprivation. Relative counts (IEL/100 epithelial cells), absolute counts (number of IEL per millimetre of muscularis mucosae), and the proportion of lymphocytes crossing the basement membrane have been evaluated. Both relative and absolute IEL counts were dimini...

  8. Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.

    Miettinen, A.; Karttunen, T J; Alavaikko, M.


    Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number o...

  9. Spontaneous unscheduled DNA synthesis in human lymphocytes

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

  10. Autoreactive lymphocytes in thyroid disorders. 2

    Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radioimmune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 x 106/ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion. (author)