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Sample records for adult lymphocyte depletion

  1. Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients.

    PubMed

    Crowson, Cole N; Reed, Rhiannon D; Shelton, Brittany A; MacLennan, Paul A; Locke, Jayme E

    2017-02-01

    The use of lymphocyte-depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high-risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first-time pediatric KT recipients using SRTR data (2000-2014). Characteristics were compared across race using Wilcoxon rank-sum tests for continuous and chi-square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte-depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52-0.83 P < .001) compared to AA recipients receiving anti-IL-2 receptor antibody induction. This difference was not seen in non-AA recipients receiving lymphocyte-depleting induction (RR, 0.93; 95% CI, 0.81-1.06, P = .26) compared to IL-2 induction. These findings support a role for lymphocyte-depleting induction agents in AA pediatric patients undergoing KT and continued use of IL-2 inhibitor induction in non-AA pediatric KT recipients.

  2. Peripheral Blood Lymphocyte Depletion After Hepatic Arterial {sup 90}Yttrium Microsphere Therapy for Hepatocellular Carcinoma

    SciTech Connect

    Carr, Brian I.; Metes, Diana M.

    2012-03-01

    Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in addition to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.

  3. Depletion of long-lived lymphocytes in old New Zealand black mice

    PubMed Central

    Denman, A. M.; Denman, Evelyn J.

    1970-01-01

    Labelling studies with tritiated thymidine in NZB mice revealed that old mice of this strain with established Coombs positive haemolytic anaemia were depleted predominantly of long-lived small lymphocytes. Lymphopoiesis in the bonemarrow was relatively less affected suggesting that the peripheral destruction or deviation of re-circulating lymphocytes and not a precursor cell deficiency may account for the depletion of these cells. Old NZB mice in which the development of Coombs positive haemolytic anaemia, but not other disease features, has been prevented by thymectomy and treatment with anti-lymphocyte globulin several months earlier were equally deficient in this population of lymphocytes. C57BL mice, subjected to the same regime largely regenerated this population during the subsequent 12 months and rejected skin homografts in the same time as young controls of the same strain. Loss of lymphocytes responsible for antigen recognition would account for the impaired cellular immunity of old NZB mice observed in this study and described earlier by other authors. This process appears to accompany the progression of the spontaneous disease in this strain. ImagesFig. 2Fig. 3 PMID:4920597

  4. Mechanism of depletion of T lymphocytes from the spleen of mice infected with Listeria monocytogenes.

    PubMed Central

    Chan, Y Y; Cheers, C

    1982-01-01

    Marked changes in the splenic lymphocyte populations during murine infection with Listeria monocytogenes were observed histologically and quantitated by the immunofluorescence of Thy-1+ immunoglobulin (Ig-) (T) and Ig+ (B) cells. Cells were depleted from the T-dependent areas of the spleen, and the number of T cells in suspensions prepared from spleens of mice 1 to 3 days after primary or secondary infection were less than 1/10 of normal. High numbers of alcohol-killed Listeria sp. did not cause any depletion. Depletion was not prevented by adrenalectomy. Although injected radiolabeled T cells distributed normally between spleen, liver, lymph node, and gut in infected mice, there appeared to be a barrier to their entry into depleted T-dependent areas of the spleen. Evidence for the destruction of T cells, but not of B cells, in the infected mouse spleen was obtained. Images PMID:6982869

  5. In vivo depletion of lymphotoxin-alpha expressing lymphocytes inhibits xenogeneic graft-versus-host-disease.

    PubMed

    Chiang, Eugene Y; Kolumam, Ganesh; McCutcheon, Krista M; Young, Judy; Lin, Zhonghua; Balazs, Mercedesz; Grogan, Jane L

    2012-01-01

    Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic hematopoietic cell transplantation and is largely mediated by activated donor lymphocytes. Lymphotoxin (LT)-α is expressed by subsets of activated T and B cells, and studies in preclinical models demonstrated that targeted depletion of these cells with a mouse anti-LT-α monoclonal antibody (mAb) was efficacious in inhibiting inflammation and autoimmune disease. Here we demonstrate that LT-α is also upregulated on activated human donor lymphocytes in a xenogeneic model of GVHD and targeted depletion of these donor cells ameliorated GVHD. A depleting humanized anti-LT-α mAb, designated MLTA3698A, was generated that specifically binds to LT-α in both the soluble and membrane-bound forms, and elicits antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Using a human peripheral blood mononuclear cell transplanted SCID (Hu-SCID) mouse model of GVHD, the anti-human LT-α mAb specifically depleted activated LT-expressing human donor T and B cells, resulting in prolonged survival of the mice. A mutation in the Fc region, rendering the mAb incapable of mediating ADCC, abolished all in vitro and in vivo effects. These data support a role for using a depleting anti-LT-α antibody in treating immune diseases such as GVHD and autoimmune diseases.

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

    PubMed Central

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

    2009-01-01

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

  7. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    MedlinePlus

    ... in Adults About Acute Lymphocytic Leukemia (ALL) What’s New in Acute Lymphocytic Leukemia Research and Treatment? Researchers ... have the Philadelphia chromosome. Gene expression profiling This new lab technique is being studied to help identify ...

  8. Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+ T-Lymphocyte-Depleted Mice

    PubMed Central

    Samuelson, D. R.; Assouline, B.; Morre, M.; Shellito, J. E.

    2015-01-01

    Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+ T lymphocytes are critical for host defense against this infection, but in the absence of CD4+ T lymphocytes, CD8+ T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against Pneumocystis and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with Pneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to Pneumocystis murina and that administration of rhIL-7 markedly enhanced clearance of Pneumocystis in CD4-depleted mice. Additionally, we observed increased recruitment of CD8+ T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+ T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+ central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine Pneumocystis pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+ T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+ T lymphocytes. PMID:26483405

  9. Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores.

    PubMed

    Gobin, V; De Bock, M; Broeckx, B J G; Kiselinova, M; De Spiegelaere, W; Vandekerckhove, L; Van Steendam, K; Leybaert, L; Deforce, D

    2015-09-01

    Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca(2+) signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca(2+) signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca(2+) signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca(2+) stores, thereby leaving less Ca(2+) available for release upon IP3- and ryanodine-receptor activation. The Ca(2+)-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca(2+) release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.

  10. T-lymphocyte profiles in FIV-infected wild lions and pumas reveal CD4 depletion.

    PubMed

    Roelke, M E; Pecon-Slattery, J; Taylor, S; Citino, S; Brown, E; Packer, C; Vandewoude, S; O'Brien, S J

    2006-04-01

    Feline immunodeficiency virus (FIV) is a lentivirus related to human immunodeficiency virus (HIV) that causes feline AIDS in the domestic cat (Felis catus). Serological surveys indicate that at least 25 other species of cat possess antibodies that cross-react with domestic cat FIV. Most infected nondomestic cat species are without major symptoms of disease. Long-term studies of FIV genome variation and pathogenesis reveal patterns consistent with coadaptation of virus and host in free-ranging FIV-Ple-infected African lions (Panthera leo) and FIV-Pco-infected pumas (Puma concolor) populations. This report examined correlates of immunodeficiency in wild and captive lions and pumas by quantifying CD5(+), CD4(+), and CD8(+) T-cell subsets. Free-ranging FIV-Ple-infected lions had immunofluorescence flow cytometry (IFC) profiles marked by a dramatic decline in CD4(+) subsets, a reduction of the CD4(+)/CD8(+) ratio, reduction of CD8(+)beta(high) cells, and expansion of the CD8(+)beta(low) subset relative to uninfected lions. An overall significant depletion in CD5(+) T-cells in seropositive lions was linked with a compensatory increase in total CD5(-) lymphocytes. The IFC profiles were altered significantly in 50% of the seropositive individuals examined. The FIV-Pco-infected pumas had a more generalized response of lymphopenia expressed as a significant decline in total lymphocytes, CD5(+) T-cells, and CD5(-) lymphocytes as well as a significant reduction in CD4(+) T-cells. Like lions, seropositive pumas had a significant decline in CD8(+)beta(high) cells but differed by not having compensatory expansion of CD8(+)beta(low) cells relative to controls. Results from FIV-infected lions and pumas parallel human and Asian monkey CD4(+) diminution in HIV and SIV infection, respectively, and suggest there may be unrecognized immunological consequences of FIV infection in these two species of large cats.

  11. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy.

    PubMed

    Abdullah, Chowdhury S; Li, Zhao; Wang, Xiuqing; Jin, Zhu-Qiu

    2016-10-01

    T cell infiltration has been associated with increased coronary heart disease risk in patients with diabetes mellitus. Effect of modulation of T cell trafficking on diabetes-induced cardiac fibrosis has yet to be determined. Therefore, our aim was to investigate the circulatory T cell depletion-mediated cardioprotection in streptozotocin-induced diabetic cardiomyopathy. Fingolimod (FTY720), an immunomodulatory drug, was tested in wild-type (WT) C57BL/6 and recombination activating gene 1 (Rag1) knockout (KO) mice without mature lymphocytes in streptozotocin-induced type 1 diabetic model. FTY720 (0.3mg/kg/day) was administered intraperitoneally daily for the first 4weeks with interim 3weeks then resumed for another 4weeks in 11weeks study period. T lymphocyte counts, cardiac histology, function, and fibrosis were examined in diabetic both WT and KO mice. FTY720 reduced both CD4(+) and CD8(+) T cells in diabetic WT mice. FTY720-treated diabetic WT mouse myocardium showed reduction in CD3 T cell infiltration and decreased expression of S1P1 and TGF-β1 in cardiac tissue. Fibrosis was reduced after FTY720 treatment in diabetic WT mice. Rag1 KO mice exhibited no CD4(+) and CD8(+) T cells in the blood and CD3 T cells in the heart. Diabetic Rag1 KO mouse hearts appeared no fibrosis and exhibited preserved myocardial contractility. FTY720-induced antifibrosis was abolished in diabetic Rag1 KO mice. These findings demonstrate that chronic administration with FTY720 induces lymphopenia and protects diabetic hearts in WT mice whereas FTY720 increases cardiac fibrosis and myocardial dysfunction in diabetic Rag1 KO mice without mature lymphocytes.

  12. Depletion of L-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes

    PubMed Central

    García-Navas, Rósula; Munder, Markus; Mollinedo, Faustino

    2012-01-01

    L-arginine (L-Arg) deficiency results in decreased T-cell proliferation and impaired T-cell function. Here we have found that L-Arg depletion inhibited expression of different membrane antigens, including CD247 (CD3ζ), and led to an ER stress response, as well as cell cycle arrest at G0/G1 in both human Jurkat and peripheral blood mitogen-activated T cells, without undergoing apoptosis. By genetic and biochemical approaches, we found that L-Arg depletion also induced autophagy. Deprivation of L-Arg induced EIF2S1 (eIF2α), MAPK8 (JNK), BCL2 (Bcl-2) phosphorylation, and displacement of BECN1 (Beclin 1) binding to BCL2, leading to autophagosome formation. Silencing of ERN1 (IRE1α) prevented the induction of autophagy as well as MAPK8 activation, BCL2 phosphorylation and XBP1 splicing, whereas led T lymphocytes to apoptosis under L-Arg starvation, suggesting that the ERN1-MAPK8 pathway plays a major role in the activation of autophagy following L-Arg depletion. Autophagy was required for survival of T lymphocytes in the absence of L-Arg, and resulted in a reversible process. Replenishment of L-Arg made T lymphocytes to regain the normal cell cycle profile and proliferate, whereas autophagy was inhibited. Inhibition of autophagy by ERN1, BECN1 and ATG7 silencing, or by pharmacological inhibitors, promoted cell death of T lymphocytes incubated in the absence of L-Arg. Our data indicate for the first time that depletion of L-Arg in T lymphocytes leads to a reversible response that preserves T lymphocytes through ER stress and autophagy, while remaining arrested at G0/G1. Our data also show that the L-Arg depletion-induced ER stress response could lead to apoptosis when autophagy is blocked. PMID:22874569

  13. Experimental Murine Candidiasis: Pathological and Immune Responses in T-Lymphocyte-Depleted Mice

    PubMed Central

    Giger, Donald K.; Domer, Judith E.; Moser, Stephen A.; McQuitty, J. T.

    1978-01-01

    Mice depleted of T-lymphocytes by thymectomy and irradiation (TXB) and immunologically competent mice were compared for gross and histological pathology as well as immune responses after cutaneous and/or intravenous challenge with Candida albicans. In response to a first cutaneous inoculation with viable Candida, TXB, sham-operated (SXB), and unmanipulated (normal) mice, all developed lesions of comparable size, duration, and histopathology. When challenged a second time cutaneously, normal and SXB mice developed lesions which were greatly increased in size when compared with those produced by a first cutaneous infection, whereas TXB mice developed lesions comparable in size to those initiated by the first infection. Histologically, the first and second lesions in all animals were acute abscesses predominantly comprised of polymorphonuclear leukocytes. The larger second lesions in SXB and normal mice were accompanied by detectable circulating antibody and by delayed hypersensitivity. Neither circulating antibody nor delayed hypersensitivity were stimulated in the TXB mice. When challenged intravenously, all previously uninfected mice, regardless of T-cell status, were equally susceptible to C. albicans. Contrary to SXB or normal mice, however, TXB mice which had been infected cutaneously were not more resistant to a subsequent intravenous challenge as judged by 6-week survival. The results suggest that T-cells do not play a significant role in innate resistance of mice to systemic candidiasis, but that such cells are important in the development of acquired resistance. PMID:309437

  14. Transient elevation of adult hippocampal neurogenesis after dopamine depletion

    PubMed Central

    Park, June-Hee; Enikolopov, Grigori

    2010-01-01

    Degeneration of the midbrain dopaminergic neurons during Parkinson's disease (PD) may affect remote regions of the brain that are innervated by the projections of these neurons. The dentate gyrus (DG), a site of continuous production of new neurons in the adult hippocampus, receives dopaminergic inputs from the neurons of the substantia nigra (SN). Thus, depletion of the SN neurons during disease or in experimental settings may directly affect adult hippocampal neurogenesis. We show that experimental ablation of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydopyridine (MPTP) mouse model of PD results in a transient increase in cell division in the subgranular zone (SGZ) of the DG. This increase is evident for the amplifying neural progenitors and for their postmitotic progeny; our results also indicate that MPTP treatment affects division of the normally quiescent stem cells in the SGZ. We also show that L-DOPA, used in the clinical treatment of PD, while attenuating the MPTP-induced death of dopaminergic neurons, does not alter the effect of MPTP on cell division in the DG. Our results suggest that a decrease in dopaminergic signaling in the hippocampus leads to a transient activation of stem and progenitor cells in the DG. PMID:20079351

  15. Growth of mycobacterium bovis (BCG) in T lymphocyte-depleted mice.

    PubMed

    Collins, F M; Congdon, C C; Morrison, N E

    1975-01-01

    BCG Montreal (10-6 viable bacilli) injected intravenously into adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) C57Bl times C3H F1 hybrid mice induced a progressive systemic infection which killed 95% of the animals within 60 days. Control mice infected with this dose of BCG did not die. The infected THXB mice failed to develop detectable levels of tuberculin hypersensitivity although they did show considerable Arthus (3 h) reactivity. The BCG-infected THXB mice lost weight progressively, and the root spleen and root lung indices increased substantially as the infection proceeded. None of the THXB mice developed an antibacterial immune response to the systemic BCG infection, and this was reflected by the continued persistence of macroscopic lung granuloma in these animals. The BCG-infected control mice developed as many surface tubercles as did the THXB animals, but the granulomas rapidly regressed in size and numbers in the normal mice. The lung changes correlated with the amount of tritiated thymidine incorporated by the lung cells in the later stages of the BCG infection. T cell depletion depressed the early splenic peak normally seen in BCG-infected controls, but, on the other hand, there was a progressive increase in lung counts in the THXB mice as the infection progressed and this late peak was not seen in the control animals. The significance of these findings is discussed in relation to the development of antituberculous immunity by BCG-infected mice.

  16. Effect of CD4+ T lymphocyte depletion on resistance of Gulf Coast Native lambs to Haemonchus contortus infection.

    PubMed

    Peña, M T; Miller, J E; Horohov, D W

    2006-06-15

    It has been reported that CD4(+) T lymphocytes are important in acquired immunity to gastrointestinal nematode infection. Whether these lymphocytes are also involved in the immune response of naturally resistant Gulf Coast Native (GCN) sheep to Haemonchus contortus infection remains to be defined. The objective of this study was to determine the role of CD4(+) T lymphocytes in this resistance. Ten GCN lambs were randomly assigned to a control (n=5) or a treatment (n=5) group. The treatment consisted of a series of IV injections with mouse anti-ovine CD4(+) T lymphocyte monoclonal antibodies for a period of 3 weeks. After the second treatment, all lambs were experimentally infected with 10,000 H. contortus infective larvae by oral inoculation. All lambs were monitored for fecal egg counts, blood packed cell volumes, white blood cell differential counts and serum antibody responses on a weekly basis. Fluorescence-activated cell sorter (FACS) analysis was done biweekly to enumerate CD4(+) T lymphocytes in peripheral blood. Necropsies were performed at the end of the study and 10% of the contents of the gastrointestinal tract were preserved for nematode enumeration and identification. Also at necropsy, mesenteric lymph nodes were extracted and FACS analysis was run on lymphoid cells. Mean fecal egg counts on day 21 and 28 post-infection and nematode counts at necropsy of the treated group were significantly (p<0.05) higher than that of the control group. Percent CD4(+) T lymphocytes in peripheral blood was significantly (p<0.05) lower in the treatment group than in the control group from day 9 to the end of the study. No differences were found in blood packed cell volumes, white blood cell differential counts, antibody titer or lymph node CD4(+) lymphocytes between groups. Lambs depleted of their CD4(+) T lymphocytes were more susceptible to H. contortus infection than undepleted lambs. The results of this study suggest that CD4(+) T lymphocytes are associated with the

  17. Effect of indomethacin on swelling, lymphocyte influx, and cartilage proteoglycan depletion in experimental arthritis.

    PubMed Central

    Pettipher, E R; Henderson, B; Edwards, J C; Higgs, G A

    1989-01-01

    The effects of indomethacin on antigen induced arthritis in rabbits have been investigated. Arthritis was induced in the knee joints of sensitised rabbits by intra-articular injection of antigen. Swelling of the joints was measured for 14 days after antigen challenge, and groups of animals were killed on days 1, 7, or 14 for collection of synovial fluids and tissues. Indomethacin (1 mg/kg, three times daily) reduced joint swelling and the prostaglandin E2 concentrations in synovial fluid. In addition, indomethacin increased the loss of proteoglycan from articular cartilage and the numbers of lymphocytes in the inflamed synovial lining. These findings suggest that the symptomatic benefits of indomethacin and related drugs in inflammatory arthritis may be achieved at the expense of significant adverse effects on joint tissues. PMID:2782971

  18. Children's and Adults' Knowledge and Models of Reasoning about the Ozone Layer and Its Depletion.

    ERIC Educational Resources Information Center

    Leighton, Jacqueline P.; Bisanz, Gay L.

    2003-01-01

    Examines children's and adults' knowledge of the ozone layer and its depletion, whether this knowledge increases with age, and how the ozone layer and ozone hole might be structured as scientific concepts. Uses a standardized set of questions to interview children and adults in Canada. Discusses implications of the results for health…

  19. Lymphocyte-depleting induction and steroid minimization after kidney transplantation: A review.

    PubMed

    Naesens, Maarten; Berger, Stefan; Biancone, Luigi; Crespo, Marta; Djamali, Arjang; Hertig, Alexandre; Öllinger, Robert; Portolés, José; Zuckermann, Andreas; Pascual, Julio

    Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin®) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients given rATG induction, but while encouraging, the data are too sparse for firm conclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid-related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaited.

  20. Classical Hodgkin lymphoma, lymphocyte depleted type: clinicopathological analysis and prognostic comparison with other types of classical Hodgkin lymphoma.

    PubMed

    Karube, Kennosuke; Niino, Daisuke; Kimura, Yoshizo; Ohshima, Koichi

    2013-04-01

    The lymphocyte-depleted type (LD) is a morphological subtype of classical Hodgkin lymphoma (CHL), but its rarity and heterogeneous morphological character makes a definite clinicopathological identification difficult. To characterize this disease, LD cases were compared with other types of CHL. From 1982 to 2006, we collected 310 CHL cases. Among them, 29 cases were diagnosed as LD. We could additionally analyze clinical data of 157 CHL cases (including 28 LD cases) and the immunophenotype of 150 CHL cases (including 28 LD cases). We compared clinicopathological data between LD cases and other types of CHL cases and determined prognostic factors by univariate and multivariate analysis. LD showed a more progressive disease stage (stage 3/4, 64%) than other types of CHL (stage 3/4, 30%; P<0.001), more frequent B symptoms (89% vs. 40%; P<0.001) and extranodal invasion (50% vs. 11%; P<0.001), older age (median: 66 vs. 33; P<0.001), higher serum soluble interleukin 2 receptor levels (median: 8240U/ml vs. 1705U/ml; P<0.001), and much poorer prognosis regardless of the international prognostic score (IPS) (five-year overall survival: 29% vs. 86%; P<0.001). The morphological subtype of LD represented an independent prognostic factor as did age and IPS by multivariate analysis. Immunohistochemistry showed that the characteristics of Hodgkin and Reed-Sternberg (HRS) cells of LD are basically not different from those of other types of CHL in terms of CD30, CD15, and chemokine receptors, except for high-level EB-virus infection (72% vs. 41%; P=0.002). LD should be distinguished from other types of classical Hodgkin lymphoma because of its definitive clinicopathological characters.

  1. Children's and adults' knowledge and models of reasoning about the ozone layer and its depletion

    NASA Astrophysics Data System (ADS)

    Leighton, Jacqueline P.; Bisanz, Gay L.

    2003-01-01

    As environmental concepts, the ozone layer and ozone hole are important to understand because they can profoundly influence our health. In this paper, we examined: (a) children's and adults' knowledge of the ozone layer and its depletion, and whether this knowledge increases with age' and (b) how the 'ozone layer' and 'ozone hole' might be structured as scientific concepts. We generated a standardized set of questions and used it to interview 24 kindergarten students, 48 Grade 3 students, 24 Grade 5 students, and 24 adults in university, in Canada. An analysis of participants' responses revealed that adults have more knowledge than children about the ozone layer and ozone hole, but both adults and children exhibit little knowledge about protecting themselves from the ozone hole. Moreover, only some participants exhibited 'mental models' in their conceptual understanding of the ozone layer and ozone hole. The implications of these results for health professionals, educators, and scientists are discussed.

  2. Differential expression of HLA class II antigens on human fetal and adult lymphocytes and macrophages.

    PubMed Central

    Edwards, J A; Jones, D B; Evans, P R; Smith, J L

    1985-01-01

    A panel of monoclonal antibodies to monomorphic determinants of the MHC class II subregion locus products: DP, DR and DQ, was used to investigate the expression of these antigens on early lymphocytes and macrophages from human fetal liver (13-20 weeks), placenta (16 weeks and term) and cord blood, in relation to the class II phenotype of cells from adult tonsil and peripheral blood. Fetal liver sections and cell suspensions showed differential expression of class II antigens. DP was expressed at a higher frequency (11.0% of nucleated cells) than DR on lymphoid cells and macrophages from fetal liver, and DQ was either absent or expressed on less than 0.3% of nucleated cells. Consistent with this finding, DP but not DR or DQ antigens were observed on vascular elements and macrophages in the villi of 16-week placenta. At term, all three subregion locus products were expressed. Adult tonsil and peripheral blood B lymphocytes expressed DP, DR and DQ antigens with similar frequency; however, DQ was expressed at a lower frequency than DP and DR on cord blood B lymphocytes. In contrast, 30-50% macrophages from cord blood and adult peripheral blood expressed DP and DR, but fewer (5% and 18%, respectively) expressed DQ. These data suggest that class II antigens are expressed in the sequence DP, DR, DQ on developing lymphocytes. A similar sequence is suggested for macrophages. Images Figure 1 Figure 2 Figure 3 PMID:3894221

  3. Plasma vemurafenib exposure and pre-treatment hepatocyte growth factor level are two factors contributing to the early peripheral lymphocytes depletion in BRAF-mutated melanoma patients.

    PubMed

    Puszkiel, Alicja; White-Koning, Mélanie; Dupin, Nicolas; Kramkimel, Nora; Thomas-Schoemann, Audrey; Noé, Gaëlle; Chapuis, Nicolas; Vidal, Michel; Goldwasser, François; Chatelut, Etienne; Blanchet, Benoit

    2016-11-01

    The therapeutic response to vemurafenib, a BRAF serine-threonine kinase inhibitor, exhibits large variations between patients. Evaluation of factors predicting the clinical efficacy of vemurafenib may help to identify patients at high risk of non-response in the early phase of treatment. The aim of this study was to analyze the pharmacokinetics of vemurafenib by a population approach and to evaluate the relationship between plasma drug exposure and pre-treatment plasma hepatocyte growth factor (HGF) levels with clinical effects (progression-free survival (PFS), peripheral lymphocytes depletion) in patients with metastatic BRAF(V600) mutated melanoma treated with single agent vemurafenib. Concentration-time data (n=332) obtained in 44 patients were analyzed using the NONMEM program. Pre-treatment plasma levels of HGF (n=36) were assayed by ELISA method. A Cox model was used to identify prognostic factors associated with progression-free survival (PFS), and a linear regression to identify factors contributing to the depletion of peripheral lymphocytes at day 15. Steady-state pharmacokinetics of vemurafenib was described by a one compartment model with first order absorption and first order elimination. None of the tested covariates explained the inter-patient variability in CL/F. A significant decrease in total lymphocytes count was observed within the first 15days (median ratio Day15/Day0=0.66, p<0.0001). Patients with Day15/Day0 ratio below 0.66 had longer PFS (14 vs 4 months, HR=0.41, CI95%=[0.15-0.77], p=0.0095). In the multivariate Cox model analysis, ECOG PS was the only parameter independently associated with PFS (grade 1 vs 0, HR=3.26, CI95%=[1.29-8.22], p=0.01 and grade ≥2 vs 0, HR=4.77, CI95%=[1.52-14.95], p=0.007). Plasma vemurafenib exposure (p=0.046) and pre-treatment HGF levels (p=0.003) were independently associated with the total lymphocyte ratio Day15/Day0. These findings show that plasma vemurafenib exposure and pre-treatment HGF levels are two

  4. Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

    PubMed

    Waisman, Ari; Ginhoux, Florent; Greter, Melanie; Bruttger, Julia

    2015-10-01

    Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We examine different microglia depletion models, and discuss the origin of their rapid repopulation after depletion and outline important areas of future research.

  5. Sub-lethal concentrations of activated complement increase rat lymphocyte glutamine utilization and oxidation while lethal concentrations cause death by a mechanism involving ATP depletion.

    PubMed

    Bacurau, R F P; O'Toole, C E; Newsholme, P; Costa Rosa, L F B P

    2002-09-01

    Nucleated cells are more resistant to complement-mediated cell death than anucleated cells such as erythrocytes. There are few reports concerning the metabolic response of nucleated cells subjected to sub-lethal complement attack. It is possible that the rate of utilization of specific metabolic fuels by the cell is increased to enhance cell defence. We have measured the maximum activity of hexokinase, citrate synthase, glucose 6-phosphate dehydrogenase and glutaminase in rat mesenteric lymphocytes exposed to sub-lethal concentrations of activated complement (present in zymosan-activated serum, ZAS). These enzymes were carefully selected as they indicate changes of flux in glycolysis, TCA cycle, pentose phosphate pathway and glutaminolysis, respectively. The only enzyme activity to change on exposure of lymphocytes to ZAS was glutaminase, which was enhanced approximately by two-fold. Although rates of both glutamine and glucose utilization were enhanced by exposure to ZAS, only the rate of oxidation of glutamine was increased. Complement kills anucleated cells by simple osmotic lysis. However, it is likely that some nucleated cells will display characteristics of an ordered death mechanism and we have demonstrated that the concentration of lymphocyte ATP is dramatically decreased by activated complement. Nevertheless, the extent of cell death could be significantly reduced by the addition of inhibitors of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). We conclude that glutamine metabolism is not only important for lymphocyte proliferative responses but is also important for cell defence from sub-lethal concentrations of activated complement. The rapid rate of complement-induced lymphocyte death reported here is suggested to be a consequence of over-activation of the nuclear enzyme PARP and ATP depletion.

  6. Apoptotic depletion of infiltrating mucosal lymphocytes associated with Fas ligand expression by Helicobacter pylori-infected gastric mucosal epithelium: human glandular stomach as a site of immune privilege.

    PubMed

    Koyama, S

    2000-04-01

    H. pylori infection almost invariably results in chronic gastritis, but only a proportion of patients develops severe destruction of epithelial glandular structure or peptic ulcer. To confirm the recent data obtained in testis and eye, showing that Fas ligand is involved in the phenomenon of "immune privilege," expression of Fas receptor and its ligand of the stomach was investigated in a panel of gastric biopsies obtained from patients H. pylori-positive (N = 42) and with H. pylori-negative (N = 18) by two-color flow cytometry. The results show that membrane-bound Fas ligand protein is constitutively expressed on freshly isolated human gastric mucosal epithelium coupled with infiltrating lymphocytes. There was significant overexpression of Fas receptor and its ligand, and a higher frequency of apoptotic cell death detected by TUNEL in epithelium and infiltrating lymphocytes in H. pylori-infected patients. These findings suggest that involvement of Fas receptor and its ligand system contributes to some extent to mucosal damage in H. pylori-associated gastritis. However, the more specific findings are apoptotic depletion of invading mucosal lymphocytes associated with Fas ligand expression by gastric epithelium. These provide the first direct quantitative evidence to support Fas receptor counterattack and/or paracrine fratricide as a mechanism of immune privilege in vivo in the H. pylori-infected glandular stomach.

  7. Long-term effects of histidine depletion on whole-body protein metabolism in healthy adults.

    PubMed

    Kriengsinyos, Wantanee; Rafii, Mahroukh; Wykes, Linda J; Ball, Ronald O; Pencharz, Paul B

    2002-11-01

    The essentiality of histidine in healthy adults is a controversial topic. To study the potential metabolic effects of a lack of exogenous histidine, four healthy adults consumed a histidine-free diet, with adequate energy and 1.0 g/(kg. d) of an L-amino acid mixture for 48 d. Protein metabolism was monitored every 4 d by using indicator amino acid (L-[1-(13)C]phenylalanine) oxidation (in four subjects) and [(15)N]glycine (in one subject). Urine samples (24-h) were collected for measurement of urea, total nitrogen, creatinine, 3-methylhistidine (3-MH), histidine and beta-alanine. Albumin, transferrin and hematologic concentrations were measured on d 0, 24 and 48. Urinary excretion of nitrogen, urea, creatinine and 3-MH were not affected by the histidine-free diet. However, there was a significant (P < 0.001) linear decline (24-28%) in whole-body protein turnover. Significant (P < 0.05) decreases in albumin (12%), transferrin (17%) and hemoglobin (Hb) (11%) concentrations occurred slowly over the histidine depletion period. The urinary excretion of beta-alanine (an index of carnosine catabolism) generally increased in the smallest subject during the consumption of histidine-free diet. This study demonstrates that a lack of histidine in the diet for a prolonged period resulted in an accommodation of protein turnover and phenylalanine oxidation, measured by the (13)C-phenylalanine indicator amino acid. The extensive metabolic accommodation, together with decreases in Hb, albumin and transferrin during histidine depletion, leaves unresolved the issue of whether histidine is a dietary essential amino acid in healthy adults.

  8. [Reference intervals for peripheral blood lymphocyte subsets in healthy adults in Lima, Peru].

    PubMed

    Cóndor, José M; Álvarez, Marco; Cano, Luis; Matos, Edgar; Leiva, Christian; Paredes, José A

    2013-04-01

    In order to establish the reference intervals (RIs) of peripheral blood lymphocyte subsets (PBL) in healthy adults in Lima (Peru), a cross-sectional study was conducted among blood donors taken in between 2011 and 2012. Based on the criteria obtained from the guidelines of the Clinical and Laboratory Standards Institute (CLSI C28-A3), 318 samples were processed, 61.9% (197/318) coming from male donors. For PBL count, a flow cytometer with a simple platform was used. The RIs are established for each PBL in adults based on sex with their respective reference limits and 90% confidence intervals. Differences were found in CD3+ percentage counts (p=0.001) and in CD3-CD56+ absolute (p=0.003) and percentage counts (p?0.001). The RIs found are different to those described in studies conducted in other countries due to the characteristics of the population and the study model.

  9. Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction

    PubMed Central

    Truskaite, Kotryna

    2016-01-01

    Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17–96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI. PMID:27547221

  10. Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction.

    PubMed

    Truskaite, Kotryna; Dlugosz, Aldona

    2016-01-01

    Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17-96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI.

  11. Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.

    PubMed

    Tonon, Sandrine; Badran, Bassam; Benghiat, Fleur Samantha; Goriely, Stanislas; Flamand, Véronique; Willard-Gallo, Karen; Willems, Fabienne; Goldman, Michel; De Wit, Dominique

    2006-07-01

    Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA(+)CD4(+) T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-alpha and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4(+) T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-gamma by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-kappaB and NFAT transcription factors. Overall, responses of neonatal CD4(+) T cells to PTX were similar to those of adult CD45RA(+)CD4(+) naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T lymphocytes in addition to activation of antigen-presenting cells.

  12. Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses.

    PubMed

    Nyström, Sofia N; Bourges, Dorothée; Garry, Sarah; Ross, Ellen M; van Driel, Ian R; Gleeson, Paul A

    2014-12-01

    Depletion of Foxp3(+) CD4(+) regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg-cell depletion on self-reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4(+) T-cell responses to endogenous self-antigens. Short-term ablation of Treg cells in mice resulted in rapid activation of CD4(+) T cells, increased percentage of IFN-γ(+) and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self-reactive responses, we analyzed the activation of naïve gastric-specific CD4(+) T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric-specific T cells in the stomach draining LNs of Treg-cell-depleted mice, compared with untreated mice, either during Treg-cell depletion or after Treg-cell reconstitution. Moreover, the hyperproliferation of gastric-specific T cells in the Treg-cell-ablated mice was predominantly antigen-dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg-cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg-cell depletion results in ongoing antigen-driven self-reactive T-cell responses and emphasize the continual requirement for an intact Treg-cell population.

  13. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  14. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  15. Human T cell priming assay: depletion of peripheral blood lymphocytes in CD25(+) cells improves the in vitro detection of weak allergen-specific T cells.

    PubMed

    Vocanson, Marc; Achachi, Amine; Mutez, Virginie; Cluzel-Tailhardat, Magalie; Varlet, Béatrice Le; Rozières, Aurore; Fournier, Philippe; Nicolas, Jean-François

    2014-01-01

    To develop an in vitro assay that recapitulates the key event of allergic contact dermatitis (ACD), that is the priming of effector T cells by hapten-presenting dendritic cells, and then allows for the sensitive detection of chemical allergens represents a major challenge. Classical human T cell priming assays (hTCPA) that have been developed in the past, using hapten-loaded monocyte-derived dendritic cells (MDDCs) as antigen-presenting cells and peripheral blood lymphocytes (PBLs) as responding cells, were not efficient to prime T cells to common allergens with moderate/weak sensitizing properties. Recent progress in the understanding of the effector and regulatory mechanisms of ACD have shown that T cell priming requires efficient uptake of allergens by immunogenic DCs and that it is controlled by several subsets of regulatory cells including CD25(+) Tregs. We therefore analyzed various parameters involved in allergen-specific T cell activation in vitro and showed that priming of allergen-specific T cells is hampered by several subsets of immune cells comprising CD1a(neg) DCs, CD25(+) T cells, and CD56(+) regulatory cells.CD4(+)CD25(+)FoxP3(+) Tregs prevented the in vitro T cell priming to moderate/weak allergens, and depletion of human PBLs in CD25(+) cells significantly increased specific T cell proliferation and IFN-γ secretion. CD56(+) cells exerted an additional control of T cell priming since co-depletion of both CD56(+) and CD25(+) cells improved the magnitude of chemical-specific T cell activation. Finally, CD1a(low) MDDCs were able to inhibit T cell activation obtained by allergen-pulsed CD1a(high) MDDC. Moreover, we showed that uptake by DC of allergen-encapsulated nanoparticles significantly increased their activation status and their ability to prompt specific T cell activation. Hence, by combining the different strategies, i.e., depletion of CD25(+) and CD56(+) cells, use of CD1a(high) MDDC, and nanoparticle encapsulation of allergens, it was

  16. Discordant lymphocyte-depleted classical Hodgkin's and peripheral T-cell lymphoma arising in a patient 11 years after diagnosis of multicentric Castleman's disease.

    PubMed

    Park, Joonhong; Lee, Ji Eun; Kim, Myungshin; Lim, Jihyang; Kim, Yonggoo; Han, Kyungja; Park, Gyeongsin; Jung, Young Hee; Roh, Sang Young; Hong, Young Seon

    2013-07-01

    Castleman's disease (CD) is thought to be related with an initially benign viral disease with cytokine-driven propagation and malignant transformation. This paper reports the first case of a simultaneous discordant lymphoma consisting of lymphocyte-depleted classical Hodgkin's lymphoma (LDCHL) and peripheral T-cell lymphoma (PTCL) arising in a patient with multicentric CD (MCD). PTCL occurred 4 years after the diagnosis of MCD, and LDCHL was developed 6 years after the treatment of PTCL, sequentially. The following year, the patient presented with a relapse of a simultaneous discordant lymphoma. On excisional cervical LN biopsy, immunohistochemical stain pattern was identical with previously diagnosed LDCHL, which expressed CD30, CD15, PAX5, and Epstein-Barr virus (EBV)-encoded RNA. PTCL was positive for CD3, CD4, CD5, CD10, and CD56, and showed identical TCRB and TCRG gene rearrangements to those detected initially. MCD was thought to be the major contributing factor leading to initial PTCL, while EBV-positive LDCHL is thought to have promoted the development of PTCL, as a persistently abnormal immune microenvironment may induce the recurrence of PTCL. MCD runs a more aggressive course and can progress to Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or combined HL/NHL. Due to its malignant potential, prompt recognition and therapy is critical for these situations, which may be life threatening.

  17. Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

    PubMed

    Ueda, S; Sakakibara, S; Yoshimoto, K

    2005-01-01

    The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

  18. Depletion of naïve lymphocytes with fas ligand ex vivo prevents graft-versus-host disease without impairing T cell support of engraftment or graft-versus-tumor activity.

    PubMed

    Askenasy, Nadir; Mizrahi, Keren; Ash, Shifra; Askenasy, Enosh M; Yaniv, Isaac; Stein, Jerry

    2013-02-01

    Graft-versus-host disease (GVHD) can be prevented by Fas-mediated selective depletion of host-sensitized donor lymphocytes ex vivo. We tested the hypothesis that Fas-mediated depletion of lymphocytes in the absence of host-specific antigenic stimulation can alleviate GVHD. Brief exposure (24 hours) of unstimulated donor lymphocytes to Fas ligand (FasL) ex vivo results in balanced apoptosis of CD8(+) and CD4(+) subsets with preferential depletion of CD62L and CD69, increased T regulatory fractions, and sustained responses to stimulation. This procedure ameliorates weight loss and improves the clinical and histologic score of skin and gastrointestinal GVHD with and without concurrent transplantation of hematopoietic progenitors and irrespective of conditioning-induced tissue injury. Although FasL-resistant donor T cells are less potent effectors of GVHD, they facilitate hematopoietic progenitor engraftment when infused with or after the graft and retain the potential to elaborate graft-versus-tumor reactions. These findings in a preclinical model together with the known trophic effects of FasL on primitive hematopoietic progenitors suggest that brief ex vivo incubation of hematopoietic grafts with FasL may improve the outcome and safety of clinical T cell-replete allogeneic and haploidentical transplants.

  19. Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

    PubMed

    Bakhmutsky, Marina V; Squibb, Katherine; McDiarmid, Melissa; Oliver, Marc; Tucker, James D

    2013-10-09

    Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

  20. Effects of dietary tryptophan and phenylalanine–tyrosine depletion on phasic alertness in healthy adults – A pilot study

    PubMed Central

    Hildebrand, Patricia; Königschulte, Werner; Gaber, Tilman Jakob; Bubenzer-Busch, Sarah; Helmbold, Katrin; Biskup, Caroline Sarah; Langen, Karl-Josef; Fink, Gereon Rudolf; Zepf, Florian Daniel

    2015-01-01

    Background The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight–adapted dietary tryptophan and phenylalanine–tyrosine depletion (PTD) techniques were used. Methods The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. Results Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same

  1. Comparative study of quality of life of adult survivors of childhood acute lymphocytic leukemia and Wilms’ tumor

    PubMed Central

    de Souza, Clélia Marta Casellato; Cristofani, Lilian Maria; Cornacchioni, Ana Lucia Beltrati; Odone, Vicente; Kuczynski, Evelyn

    2015-01-01

    Abstract Objective To analyze and compare the health-related quality of life of adult survivors of acute lymphocytic leukemia and Wilms’ tumor amongst themselves and in relation to healthy participants. Methods Ninety participants aged above 18 years were selected and divided into three groups, each comprising 30 individuals. The Control Group was composed of physically healthy subjects, with no cancer history; and there were two experimental groups: those diagnosed as acute lymphocytic leukemia, and those as Wilms’ Tumor. Quality of life was assessed over the telephone, using the Medical Outcomes Study 36-Item Short Form Health Survey. Results Male survivors presented with better results as compared to female survivors and controls in the Vitality domain, for acute lymphocytic leukemia (p=0.042) and Wilms’ tumor (p=0.013). For acute lymphocytic leukemia survivors, in Social aspects (p=0.031), Mental health (p=0.041), and Emotional aspects (p=0.040), the latter also for survivors of Wilms’ tumor (p=0.040). The best results related to the Functional capacity domain were recorded for the experimental group that had a late diagnosis of acute lymphocytic leukemia. There were significant differences between groups except for the Social and Emotional domains for self-perceived health, with positive responses that characterized their health as good, very good, and excellent. Conclusion Survivors of acute lymphocytic leukemia showed no evidence of relevant impairment of health-related quality of life. The Medical Outcomes Study 36-Item Short Form Health Survey (via telephone) can be a resource to access and evaluate survivors. PMID:26537509

  2. Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish.

    PubMed

    Gombeau, Kewin; Pereira, Sandrine; Ravanat, Jean-Luc; Camilleri, Virginie; Cavalie, Isabelle; Bourdineaud, Jean-Paul; Adam-Guillermin, Christelle

    2016-04-01

    We examined the effects of chronic exposure to different concentrations (2 and 20 μg L(-)(1)) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5'-CCGG-3') and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L(-)(1) DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L(-)(1) DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L(-)(1) DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects.

  3. Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

    PubMed Central

    Benninghoff, Jens; Gritti, Angela; Rizzi, Matteo; LaMorte, Giuseppe; Schloesser, Robert J; Schmitt, Angelika; Robel, Stefanie; Genius, Just; Moessner, Rainald; Riederer, Peter; Manji, Husseini K; Grunze, Heinz; Rujescu, Dan; Moeller, Hans-Juergen; Lesch, Klaus-Peter; Vescovi, Angelo Luigi

    2010-01-01

    Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors. PMID:20010549

  4. Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells.

    PubMed

    Benninghoff, Jens; Gritti, Angela; Rizzi, Matteo; Lamorte, Giuseppe; Schloesser, Robert J; Schmitt, Angelika; Robel, Stefanie; Genius, Just; Moessner, Rainald; Riederer, Peter; Manji, Husseini K; Grunze, Heinz; Rujescu, Dan; Moeller, Hans-Juergen; Lesch, Klaus-Peter; Vescovi, Angelo Luigi

    2010-03-01

    Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.

  5. The utility of cytodiagnostic urinalysis as a tool to diagnose kidney allograft dysfunction in the era lymphocyte-depleting induction therapy.

    PubMed

    Mehta, T; Sanaei-Ardekani, M; Farooqi, A; Khan, S; Shammas, A; Boonyapredee, M; Allston, C; Wu, J; Nsouli, H; Pehlivanova, M

    2011-12-01

    Cytodiagnostic urinalysis (CDU) has been used to evaluate causes of kidney allograft dysfunction, such as an acute rejection episode (ARE), calcineurin inhibitor (CNI) toxicity, or polyoma virus infection. We examined the concordance between CDU and allograft biopsy in patients with allograft dysfunction. Between 2002 and 2006, 201 patients had CDU performed within 7 days of a biopsy. The cohort was black (73%) with, male preponderance (59.2%), and an overall mean age of 48±13 years with 46% having received a deceased donor kidney. The induction regimen consisted of either antithymocyte globulin or alemtuzumab. CDU results that demonstrated 5 to 10 lymphocytes per high-power field (HPF) and >20 lymphocytes/HPF had 2.5 increased odds of predicting acute rejection (AR) on biopsy (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.12-5.79; P=.025). In the era of antithymocyte globulin induction, a CDU result demonstrating>5 lymphocytes/HPF had a 4.3 increased odds of predicting AR (CI 1.76-10.50; P=.001). This association was lost with alemtuzumab induction. A positive CDU result for calcineurin inhibitor (CNI) toxicity did not predict CNI nephrotoxcity on biopsy, but a positive CDU for polyoma virus infection predicted polyoma virus nephropathy (OR 22.18; CI: 4.41-111.63; P<.001). In conclusion, CDU is an adjunctive diagnostic tool for kidney transplantation.

  6. Depletion of CD4 T Lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A calf model was used to determine if the depletion of CD4 T cells prior to inoculation of Mycobacterium avium subsp. paratuberculosis (Map) would delay development of an immune response to Map and accelerate disease progression. Ileal cannulas were surgically implanted in 5 bull calves at two month...

  7. Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome

    PubMed Central

    Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

    2016-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B

  8. Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus

    PubMed Central

    Skucas, Vanessa A.; Duffy, Aine M.; Harte-Hargrove, Lauren; Magagna-Poveda, Alejandra; Radman, Thomas; Chakraborty, Goutam; Schroeder, Charles E.; MacLusky, Neil J.; Scharfman, H.E.

    2013-01-01

    Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation (LTP) of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms, and found that Gdx induced a long-lasting upregulation of MF brain-derived neurotrophic factor (BDNF) immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins such as BDNF, reversed the increase in MF transmission, excitability and LTP in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF transmission but 50 nM 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth, but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity. PMID:23392664

  9. Caspase-8 deficiency presenting as late-onset multi-organ lymphocytic infiltration with granulomas in two adult siblings

    PubMed Central

    Niemela, Julie; Kuehn, Hye Sun; Kelly, Corin; Zhang, Mingchang; Davies, Joie; Jose, Melendez; Dreiling, Jennifer; Kleiner, David; Calvo, Katherine; Oliveira, João B.; Rosenzweig, Sergio D.

    2015-01-01

    Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C>T, p.248R>W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients. PMID:25814141

  10. Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

    PubMed

    Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2013-06-01

    This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.

  11. Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes depleted of graft-versus-host reactivity: a new source for graft facilitating cells in bone marrow transplantation.

    PubMed

    Aviner, Shraga; Yao, Xin; Krauthgamer, Rita; Gan, Yehudit; Goren-Arbel, Rinat; Klein, Tirza; Tabilio, Antonio; McMannis, John D; Champlin, Richard; Martelli, Massimo F; Bachar-Lustig, Esther; Reisner, Yair

    2005-06-01

    Induction of donor type chimerism in mildly prepared hosts without graft-versus-host disease (GvHD) is a most desirable goal in bone morrow transplantation. We have recently demonstrated in a mouse model that donor veto cytotoxic T lymphocytes (CTLs) can facilitate the induction of donor type chimerism in sublethally irradiated recipients without causing GvHD if they are effectively depleted of alloreactivity against host cells by means of stimulation against a third party. We extend this approach to human cells, by preparing CTLs in two major steps: primary culture in the absence of interleukin 2, leading to death by neglect of antihost clones, and addition of interleukin 2 and subsequent dilution of antihost clones as a consequence of the expansion of the anti-third-party clones. CTLs prepared in this way specifically suppress host cytotoxic T cells directed against antigens of the donor, but not against fourth-party antigens, as demonstrated in a standard (51)Cr release assay. We conclude that human anti-third-party CTLs afford a new source of veto cells that are depleted of potential graft-versus-host-reactive clones. The cells generated by this approach could potentially be used to facilitate engraftment of allogeneic hematopoietic stem cells.

  12. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults

    PubMed Central

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-01-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation. PMID:26886066

  13. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

    PubMed

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  14. Proteins in the cell wall and membrane of Cryptococcus neoformans stimulate lymphocytes from both adults and fetal cord blood to proliferate.

    PubMed Central

    Mody, C H; Sims, K L; Wood, C J; Syme, R M; Spurrell, J C; Sexton, M M

    1996-01-01

    Cryptococcus neoformans is an encapsulated yeast that infects patients who have defective cell-mediated immunity, including AIDS, but rarely infects individuals who have intact cell-mediated immunity. Studies of the immune response to C. neoformans have been hampered by a paucity of defined T-lymphocyte antigens, and hence, the understanding of the T-cell response is incomplete. The goal of this study was to separate C. neoformans into its component parts, determine whether those components stimulate lymphocyte proliferation, perform preliminary characterization of the proteins, and establish the potential mechanism of lymphocyte proliferation. The lymphocyte response to fungal culture medium, whole organisms, disrupted organisms, and the yeast intracellular fraction or cell wall and membrane was studied by determining thymidine incorporation and by determining the number of lymphocytes at various times after stimulation. The cell wall and membrane of C. neoformans stimulated lymphocyte proliferation, while the intracellular fraction and culture filtrate did not. The optimal response occurred on day 7 of incubation, with 4 x 10(5) peripheral blood mononuclear cells per well and with 13 microg of cryptococcal protein per ml. The number of lymphocytes increased with time in culture, indicating that thymidine incorporation was accompanied by proliferation. Proteinase K treatment of the cell wall and membrane abrogated lymphocyte proliferation, indicating that the molecule was a protein. [35S]methionine labeling, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography were performed to analyze the proteins contained in the cell wall and membrane, intracellular fraction, and culture filtrate. At least 18 discrete bands were resolved from the cell wall and membrane. Since a large percentage of healthy adults responded to the cryptococcal cell wall and membrane, a mitogenic effect was investigated by testing proliferation of fetal cord blood

  15. Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy

    PubMed Central

    Naranbhai, Vivek; Hill, Adrian V. S.; Abdool Karim, Salim S.; Naidoo, Kogieleum; Abdool Karim, Quarraisha; Warimwe, George M.; McShane, Helen; Fletcher, Helen

    2014-01-01

    Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis. PMID:24041796

  16. Establishment of reference values of CD4 and CD8 lymphocyte subsets in healthy Nigerian adults.

    PubMed

    Oladepo, D K; Idigbe, E O; Audu, R A; Inyang, U S; Imade, G E; Philip, A O; Okafor, G O; Olaleye, D; Mohammed, S B; Odunukwe, N N; Harry, T O; Edyong-Ekpa, M; Idoko, J; Musa, A Z; Adedeji, A; Nasidi, A; Ya'aba, Y; Ibrahim, K

    2009-09-01

    A total of 2,570 apparently healthy human immunodeficiency virus-negative adults from the six geopolitical zones in the country were enrolled in our study in 2006. The samples were assayed using the Cyflow technique. Data were analyzed using the Statistical Package for Social Scientists (SPSS). The majority (64%) of the participants had CD4 counts within the range of 501 to 1,000 cells/microl. The reference range for CD4 was 365 to 1,571 cells/microl, while the reference range for CD8 was 145 to 884 cells/microl.

  17. Ratios of T lymphocyte subpopulations predict survival of cadaveric renal allografts in adult patients on low dose corticosteroid therapy.

    PubMed

    Van Es, A; Tanke, H J; Baldwin, W M; Oljans, P J; Ploem, J S; Vanes, L A

    1983-04-01

    Peripheral blood T lymphocyte subpopulations were monitored in 45 consecutive adult recipients of cadaveric renal allografts by using monoclonal antibodies and flow cytometrie. All patients were treated with low dose corticosteroids and azathioprine. In 37 patients pre-transplant OKT4/OKT8 ratios were available. Six of 26 patients (23%) with pre-transplant OKT4/OKT8 ratios greater than 1.6 and seven of 11 patients (64%) with pre-transplant OKT4/OKT8 ratio less than or equal to 1.6 lost their graft due to rejection within 6 months. The difference in transplant survival between patients with pre-transplant OKT4/OKT8 ratios greater than 1.6 and less than or equal to 1.6i is just significant (P = 0 . 049 Fishers test). No correlation was found between post-transplant values of individual lymphocyte subpopulations or OKT4/OKT8 ratios and the incidence of subsequent rejection episodes. Forty out of 45 patients suffered one or more rejection episodes which were treated by raising the dosage of prednisone. In 24 of these patients the rejection episode was reversed, leading to a transplant survival of at least 6 months. In these 24 patients the OKT4/OKT8 ratio was greater than 1.6 for at least 3 days before the institution of any rejection treatments. Sixteen patients lost their graft due to rejection within 6 months after transplantation. In 11 of these 16 patients OKT4/OKT8 ratios less than or equal to 1.6 preceded the institution of all rejection treatments for at least 3 days, while in three patients the OKT4/OKT8 ratio was greater than 1.6 before the first rejection episode but this ratio was less than or equal to 1.6 before subsequent rejection episodes. Thus, OKT4/OKT8 ratios greater than 1.i6 correlated with reversible rejection episodes and OKT4/OKT8 ratios less than or equal to 1.6 correlated with irreversible rejection (P less than 0 . 001).

  18. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511.

    PubMed

    Wetzler, Meir; Sanford, Ben L; Kurtzberg, Joanne; DeOliveira, Divino; Frankel, Stanley R; Powell, Bayard L; Kolitz, Jonathan E; Bloomfield, Clara D; Larson, Richard A

    2007-05-15

    CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.

  19. Sarcoplasmic reticulum Ca2+ depletion in adult skeletal muscle fibres measured with the biosensor D1ER.

    PubMed

    Jiménez-Moreno, Ramón; Wang, Zhong-Ming; Messi, María Laura; Delbono, Osvaldo

    2010-04-01

    The endoplasmic/sarcoplasmic reticulum (ER/SR) plays a crucial role in cytoplasmic signalling in a variety of cells. It is particularly relevant to skeletal muscle fibres, where this organelle constitutes the main Ca2+ store for essential functions, such as contraction. In this work, we expressed the cameleon biosensor D1ER by in vivo electroporation in the mouse flexor digitorum brevis (FDB) muscle to directly assess SR Ca2+ depletion in response to electrical and pharmacological stimulation. The main conclusions are: (1) D1ER is expressed in the SR of FDB fibres according to both di-8-(amino naphthyl ethenyl pyridinium) staining experiments and reductions in the Förster resonance energy transfer signal consequent to SR Ca2+ release; (2) the amplitude of D1ER citrine/cyan fluorescent protein (CFP) ratio evoked by either 4-chloro-m-cresol (4-CmC) or electrical stimulation is directly proportional to the basal citrine/CFP ratio, which indicates that SR Ca2+ modulates ryanodine-receptor-isoform-1-mediated SR Ca2+ release in the intact muscle fibre; (3) SR Ca2+ release, measured as D1ER citrine/CFP signal, is voltage-dependent and follows a Boltzmann function; and (4) average SR Ca2+ depletion is 20% in response to 4-CmC and 6.4% in response to prolonged sarcolemmal depolarization. These results indicate that significantly depleting SR Ca2+ content under physiological conditions is difficult.

  20. Age Shall Not Weary Us: Deleterious Effects of Self-Regulation Depletion Are Specific to Younger Adults

    PubMed Central

    Dahm, Theresa; Neshat-Doost, Hamid Taher; Golden, Ann-Marie; Horn, Elizabeth; Hagger, Martin; Dalgleish, Tim

    2011-01-01

    Self-regulation depletion (SRD), or ego-depletion, refers to decrements in self-regulation performance immediately following a different self-regulation-demanding activity. There are now over a hundred studies reporting SRD across a broad range of tasks and conditions. However, most studies have used young student samples. Because prefrontal brain regions thought to subserve self-regulation do not fully mature until 25 years of age, it is possible that SRD effects are confined to younger populations and are attenuated or disappear in older samples. We investigated this using the Stroop color task as an SRD induction and an autobiographical memory task as the outcome measure. We found that younger participants (<25 years) were susceptible to depletion effects, but found no support for such effects in an older group (40–65 years). This suggests that the widely-reported phenomenon of SRD has important developmental boundary conditions casting doubt on claims that it represents a general feature of human cognition. PMID:22039469

  1. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant.

    PubMed

    McIver, Zachariah; Melenhorst, Jan Joseph; Wu, Colin; Grim, Andrew; Ito, Sawa; Cho, Irene; Hensel, Nancy; Battiwalla, Minoo; Barrett, Austin John

    2013-03-01

    Delayed immune recovery is a characteristic feature of allogeneic hematopoietic stem cell transplantation in adult recipients. Although recipient thymic T-cell neogenesis contributes to T-cell regeneration after transplantation, thymic recovery in the transplant recipient decreases with increasing age, and is diminished by intensive preconditioning regimens and graft-versus-host disease. In adult recipients, most events that determine transplant success or failure occur during the period when the majority of circulating T cells is derived from the donor's post thymic T-cell repertoire. As a result, the make-up of the donor lymphocyte compartment may strongly influence immune recovery and transplant outcomes. The aim of this study was to examine donor lymphocyte counts in a series of patients undergoing an allogeneic hematopoietic stem cell transplant to identify the potential contribution of donor regulatory and conventional T lymphocyte populations to immune recovery and transplant outcomes. We examined donor lymphocyte subset counts in relation to post-transplant lymphocyte recovery and transplant events in 220 consecutive myeloablative, T-cell-depleted, HLA-identical sibling hematopoietic stem cell transplant recipients with hematologic malignancies. In a multivariate analysis, absolute numbers of donor CD4(+) recent thymic emigrants were associated with overall survival (P=0.032). The donors' absolute lymphocyte count and thymic production of regulatory T cells were both associated with extensive chronic graft-versus-host disease (P=0.002 and P=0.022, respectively). In conclusion, these results identify donor immune characteristics that are associated with lymphocyte recovery, extensive chronic graft-versus-host disease, and survival in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using peripheral blood samples drawn from donors and patients enrolled in the ClinicalTrials.gov-registered trials

  2. NNKTT120, an anti-iNKT cell monoclonal antibody, produces rapid and sustained iNKT cell depletion in adults with sickle cell disease

    PubMed Central

    Majerus, Elaine; Ataga, Kenneth I.; Vichinsky, Elliot P.; Schaub, Robert; Mashal, Robert; Nathan, David G.

    2017-01-01

    Invariant NKT (iNKT) cells can be activated to stimulate a broad inflammatory response. In murine models of sickle cell disease (SCD), interruption of iNKT cell activity prevents tissue injury from vaso-occlusion. NKTT120 is an anti-iNKT cell monoclonal antibody that has the potential to rapidly and specifically deplete iNKT cells and, potentially, prevent vaso-occlusion. We conducted an open-label, multi-center, single-ascending-dose study of NKTT120 to determine its pharmacokinetics, pharmacodynamics and safety in steady-state patients with SCD. Doses were escalated in a 3+3 study design over a range from 0.001 mg/kg to 1.0 mg/kg. Twenty-one adults with SCD were administered NKTT120 as part of 7 dose cohorts. Plasma levels of NKTT120 predictably increased with higher doses. Median half-life of NKTT120 was 263 hours. All subjects in the higher dose cohorts (0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg) demonstrated decreased iNKT cells below the lower limit of quantification within 6 hours after infusion, the earliest time point at which they were measured. In those subjects who received the two highest doses of NKTT120 (0.3, 1 mg/kg), iNKT cells were not detectable in the peripheral blood for a range of 2 to 5 months. There were no serious adverse events in the study deemed to be related to NKTT120. In adults with SCD, NKTT120 produced rapid, specific and sustained iNKT cell depletion without any infusional toxicity or attributed serious adverse events. The next step is a trial to determine NKTT120’s ability to decrease rate of vaso-occlusive pain episodes. Trial Registration: clinicaltrials.gov NCT01783691. PMID:28152086

  3. [Anomalies in fatty acids distribution and superoxide dismutase activity in lymphocytes of an adult with atypical ceroid lipofuscinosis].

    PubMed

    Rumbach, L; Warter, J M; Coquillat, G; Marescaux, C; Collard, M; Rohmer, F; Bieth, R; Zawislak, R

    1983-01-01

    A 27-year-old Algerian patient presented a slowly progressive disease clinically characterized by a cerebellar syndrome, absence of deep reflexes, bilateral sign of Babinski, deep sensory disturbances, ophthalmologic disorders and pes cavus. The diagnosis of ceroid lipofuscinosis resulted from the presence of lipofuscin deposits evidenced as autofluorescent bodies, and a particular type of curvilinear, crystalloid ultrastructural inclusion bodies in muscle, lymphocytes and liver. Biochemical tests showed reduction in levels of linoleic and arachidonic acids, and of superoxide dismutase activity in lymphocytes. These findings suggest that the biochemical anomalies result from disturbances in polyunsaturated fatty acids metabolism. These results can be related to pathogenetic hypotheses for ceroid lipofuscinosis suggesting a predominant role for peroxidation of fatty acids.

  4. Clofarabine in Adult Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-02-04

    Solid Tumors; Leukemia, Lymphocytic, Acute, Pediatric; Leukemia, Lymphocytic, Acute, Adult; Leukemia, Myelocytic, Acute, Pediatric; Leukemia, Myelocytic, Acute, Adult; Myelodysplastic Syndromes, Adult

  5. EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults.

    PubMed

    Huppmann, Alison R; Nicolae, Alina; Slack, Graham W; Pittaluga, Stefania; Davies-Hill, Theresa; Ferry, Judith A; Harris, Nancy Lee; Jaffe, Elaine S; Hasserjian, Robert P

    2014-03-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL) are classified separately because of their distinct clinical and pathologic features. Whereas Epstein-Barr virus (EBV) is detected in the neoplastic cells of 25% to 70% of CHL, NLPHL is generally considered to be EBV(-). We assessed EBV status in 302 pediatric and adult cases of NLPHL. A total of 145 pediatric (age 18 y or younger) and 157 adult cases of NLPHL were retrieved from 3 North American centers and tested for EBV by in situ hybridization (EBV-encoded small RNA). Clinical and pathologic features were analyzed. Five (3.4%) pediatric and 7 (4.5%) adult NLPHL cases contained EBV(+) lymphocyte-predominant (LP) cells. Although all 12 cases met the criteria for diagnosis of NLPHL, atypical features were present, including capsular fibrosis, atrophic germinal centers, and pleomorphic or atypical LP cells. CD20 and OCT-2 were strongly and diffusely positive in all except 1 case. However, PAX5 and CD79a were weak and/or variable in 7/8 and 6/6 cases tested, respectively. EBV(+) cases were more likely to be CD30(+) (75%) compared with EBV(-) cases (25%) (P=0.0007); CD15 was negative in all cases. Our results show that EBV(+) LP cells may occur in NLPHL. Distinguishing EBV(+) NLPHL from CHL can be challenging, as EBV(+) NLPHL can have partial expression of CD30 and weak PAX5 staining as well as pleomorphic-appearing LP cells. However, the overall appearance and maintenance of B-cell phenotype, with strong and diffuse CD20 and OCT-2 expression, support the diagnosis of NLPHL in these cases.

  6. A comparison of murine T-cell-depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution.

    PubMed

    Chen, Benny J; Cui, Xiuyu; Sempowski, Gregory D; Gooding, Maria E; Liu, Congxiao; Haynes, Barton F; Chao, Nelson J

    2002-01-01

    Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery using an animal model of bone marrow and cord blood as sources of stem cells, hematopoietic engraftment and immune recovery were studied following infusion of T-cell-depleted adult bone marrow or full-term fetal blood cells, as a model of cord blood in a murine allogeneic transplantation model (C57BL/6 [H-2(b)] --> BALB/c [H-2(d)]). Allogeneic full-term fetal blood has poorer radioprotective capacity but greater long-term engraftment potential on a cell-to-cell basis compared with T-cell-depleted bone marrow. Allogeneic full-term fetal blood recipients had decreased absolute numbers of T, B, and dendritic cells compared with bone marrow recipients. Splenic T cells in allogeneic full-term fetal blood recipients proliferated poorly, were unable to generate cytotoxic effectors against third-party alloantigens in vitro, and failed to generate alloantigen-specific cytotoxic antibodies in vivo. In addition, reconstituting T cells in fetal blood recipients had decreased mouse T-cell receptor delta single-joint excision circles compared with bone marrow recipients. At a per-cell level, B cells from fetal blood recipients did not proliferate as well as those found in bone marrow recipients. These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution.

  7. The Toxicity of Depleted Uranium

    PubMed Central

    Briner, Wayne

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed. PMID:20195447

  8. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: effect of prednisone treatment.

    PubMed

    López-Karpovitch, Xavier; Graue, Gerardo; Crespo-Solís, Erick; Piedras, Josefa

    2008-07-01

    High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.

  9. Negative depletion of α/β+ T cells and of CD19+ B lymphocytes: a novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation.

    PubMed

    Locatelli, Franco; Bauquet, Aurelie; Palumbo, Giuseppe; Moretta, Francesca; Bertaina, Alice

    2013-01-01

    In recent years, infusion of T-cell depleted hematopoietic stem cells from an HLA-haploidentical relative has been shown to represent a suitable and effective, alternative option in patients in need of an allograft who lack an HLA-identical relative. In particular, this type of allograft is associated with the enormous advantage of offering an immediate transplant treatment to virtually all pediatric patients without an HLA-matched donor, whether related or unrelated, or a suitable umbilical cord blood unit. Several studies have shown that in patients given a T-cell depleted transplant relevant part of the anti-leukemia effect is mediated by alloreactive (i.e. KIR/HLA mismatched) Natural Killer cells originated from donor hematopoietic stem cells. After infusion of positively selected hematopoietic stem cell, fully functioning Natural Killer cells emerge in the recipient peripheral blood, persisting over time, only several weeks after the allograft. We have developed a new method of T-cell depletion (based on the physical elimination of mature T cells carrying α and β chains of the T-cell receptor), which permits to maintain mature donor-derived alloreactive Natural Killer cells and γδ(+) T cells in the graft. We, thus, started a formal study in children with hematological disorders aimed at evaluating the safety and efficacy of this approach. Preliminary results on 60 children transplanted so far after this type of graft manipulation are particularly promising.

  10. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

    PubMed Central

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C.; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G.

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world’s population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6–9 weeks of age, and were necropsied at 27–29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use

  11. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    PubMed

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp

  12. Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes.

    PubMed Central

    Seto, S; Carrera, C J; Kubota, M; Wasson, D B; Carson, D A

    1985-01-01

    Deoxyadenosine has been implicated as the toxic metabolite causing profound lymphopenia in immunodeficient children with a genetic deficiency of adenosine deaminase (ADA), and in adults treated with the potent ADA inhibitor deoxycoformycin. However, the biochemical basis for deoxyadenosine toxicity toward lymphocytes remains controversial. The present experiments have examined in detail the sequential metabolic changes induced in nondividing human peripheral blood lymphocytes by incubation with deoxyadenosine plus deoxycoformycin, or with 2-chlorodeoxyadenosine (CdA), an ADA resistant deoxyadenosine congener with anti-leukemic and immunosuppressive properties. The lymphotoxic effect of deoxyadenosine and CdA required their phosphorylation, and was inhibited by deoxycytidine. As early as 4 h after exposure to the deoxynucleosides, strand breaks in lymphocyte DNA began to accumulate, and RNA synthesis decreased. These changes were followed by a significant fall in intracellular NAD levels at 8 h, a drop in ATP pools at 24 h, and cell death by 48 h. Incubation of the lymphocytes with 5 mM nicotinamide, a NAD precursor and an inhibitor of poly(ADP-ribose) synthetase, prevented NAD depletion. The nicotinamide treatment also rendered the lymphocytes highly resistant to deoxyadenosine and CdA toxicity, without altering dATP formation or the accumulation of DNA strand breaks. The poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide exerted a similar although less potent effect. These results suggest that NAD depletion, probably triggered by poly(ADP-ribose) formation, is the principle cause of death in normal resting human lymphocytes exposed to deoxyadenosine plus deoxycoformycin, or to CdA. PMID:2579098

  13. In vitro synthesis of IgM rheumatoid factor in response to Staphylococcus aureus, by lymphocytes from healthy adults

    SciTech Connect

    Goldstein, R.; Karsh, J.

    1986-12-01

    Peripheral blood mononuclear cells from 20 healthy adults were tested in vitro for the production of IgM rheumatoid factor (RF) in response to Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen. Fifteen of the 20 normal subjects produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 46 +/- 55 ng/ml) in response to SAC, compared with only 2 of 20 who produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 2 +/- 4 ng/ml) in response to pokeweed mitogen (P = 0.0001). Separation and reconstitution of autologous T and B cell-enriched fractions, with and without prior T cell irradiation, provided evidence for a radiosensitive T helper/inducer cell involved in the IgM-RF response to SAC in 70% of the normal subjects studied. SAC appears to be a potent stimulus of IgM-RF production, with a cellular mechanism distinct from that of other in vitro systems.

  14. Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice.

    PubMed

    Cheng, Wen-Hsing; Holmstrom, Alexandra; Li, Xiangdong; Wu, Ryan T Y; Zeng, Huawei; Xiao, Zhengguo

    2012-05-01

    Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8(+) and CD4(+) T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na(2)SeO(4)) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10(6) cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se -  or Se++ diet and the CD4(+) T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4(+) or CD8(+) T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25(+)CD4(+) T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4(+), but not CD8(+) T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.

  15. Influence of sex and estrous cycle on the effects of acute tryptophan depletion induced by a gelatin-based mixture in adult Wistar rats.

    PubMed

    Jans, L A W; Lieben, C K J; Blokland, A

    2007-06-29

    Women are more vulnerable to develop depression and anxiety disorders than men. This may be related to higher serotonergic vulnerability in women. Serotonergic vulnerability entails that differences between people in the regulation of serotonin (5-HT) determine the vulnerability of an individual to develop depression or other 5-HT-related disorders. The aim of the present experiment was to evaluate whether male and female Wistar rats differ in serotonergic vulnerability. Here, a stronger behavioral response to acute tryptophan (TRP) depletion was assumed to reflect serotonergic vulnerability. Twenty-four male and 48 female rats were repeatedly subjected to treatment with a gelatin-based protein-carbohydrate mixture, either with or without L-tryptophan. Female estrous cycle phase was determined by means of vaginal smears and the females were divided into two groups based on their estrous cycle phase: pro-estrus/estrus and met-estrus/di-estrus. Blood samples showed stronger TRP depletion in males than females. There was no effect of estrous cycle on plasma TRP concentrations. In contrast, treatment effects on some brain TRP concentrations were influenced by estrous cycle phase, females in pro-estrus/estrus showed the strongest response to TRP depletion. In the open field test and home cage emergence test, females in pro-estrus/estrus also showed the strongest behavioral response to acute TRP depletion. In general, females showed more activity than males in anxiety-related situations and this effect appeared to be enhanced by TRP depletion. In the social interaction test, passive body contact in males and females in pro-estrus/estrus was decreased after TRP depletion whereas it was increased in females in the met-estrus/di-estrus phase. Acute TRP depletion affected object recognition, but did not affect behavior in the forced swimming test and a reaction time task. It is concluded that sex and estrous cycle phase can influence the behavioral response to TRP depletion

  16. How Is Acute Lymphocytic Leukemia Classified?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Classified? Most types of cancers are assigned numbered ... ALL are now named as follows: B-cell ALL Early pre-B ALL (also called pro-B ...

  17. How Is Acute Lymphocytic Leukemia Diagnosed?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Diagnosed? Certain signs and symptoms can suggest that ... described below. Tests used to diagnose and classify ALL If your doctor thinks you have leukemia, he ...

  18. A review of supportive care and recommended preventive approaches for patients with chronic lymphocytic leukemia.

    PubMed

    Randhawa, Jasleen K; Ferrajoli, Alessandra

    2016-03-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent type of adult leukemia encountered in the western world. Patients with CLL are typically older, with a median age in the 70s, and are at risk for certain complications due to the disease itself and due to the therapies imparted for this. Patients with CLL are at a higher risk of infections, partly due to disease and partly due to the immune dysfunction induced by treatment, such as purine analogous-based chemoimmunotherapy, which leads to lymphocyte depletion. Infections are a leading cause of complications and death in CLL patients. Also, CLL patients have been shown to have a higher incidence of other malignancies. Despite this knowledge, there are no definite guidelines as to what is the best approach to manage or prevent these associated complications of CLL. In this review, the authors discuss the data available and outline recommendations as to the best way to approach this issue in daily practice.

  19. Infection of the intermediate mite host with Wolbachia-depleted Litomosoides sigmodontis microfilariae: impaired L1 to L3 development and subsequent sex-ratio distortion in adult worms.

    PubMed

    Arumugam, Sridhar; Pfarr, Kenneth M; Hoerauf, Achim

    2008-07-01

    The rodent filaria Litomosoides sigmodontis harbour Wolbachia, endosymbionts essential for worm embryogenesis, larval development and adult survival. To study the effect of tetracycline, which depletes Wolbachia, on the development of microfilariae (L1s, MF) to L3 in the intermediate host Ornithonyssus bacoti, and to observe the development of Wolbachia-depleted L3s in Mongolian gerbils (Meriones unguiculatus); microfilaremic gerbils were treated orally with tetracycline for 6 weeks (primary infected Tet) or untreated (primary Con). Treatment resulted in a significant reduction of Wolbachia per MF in primary Tet gerbils. Naïve mites then fed on the primary Tet and primary Con gerbils in the week after treatment ended, when MF levels were not significantly different, and used to infect new gerbils (secondary infected ) Tet, secondary Con) via natural infection. The infection rate from dissected mites was 9% and 54% (primary Tet and primary Con, respectively). After 3 months, worms were isolated from secondary gerbils. Significantly fewer female worms developed in secondary Tet gerbils. In contrast, there was no difference in the number of male worms that developed in secondary gerbils, resulting in a male biased sex-ratio. Although secondary Tet male worms had fewer Wolbachia than secondary Con males, development was not impaired. Female worms that developed from Wolbachia-depleted MF had Wolbachia levels equivalent to worms from secondary Con animals. Thus, tetracycline pre-treatment selected for female worms with high numbers of Wolbachia, whereas male worms had median Wolbachia levels significantly lower than secondary Con males. Therefore, female worms require a higher threshold of Wolbachia for their development. The worms analysed were only exposed to tetracycline as MF, ruling out direct effects of tetracycline during larval development in the mites or secondary gerbils, suggesting that the depletion of Wolbachia in MF was the cause of impaired larval

  20. Boron-Doped Diamond Microelectrodes Reveal Reduced Serotonin Uptake Rates in Lymphocytes from Adult Rhesus Monkeys Carrying the Short Allele of the 5-HTTLPR

    PubMed Central

    2009-01-01

    Uptake resolved by high-speed chronoamperometry on a second-by-second basis has revealed important differences in brain serotonin transporter function associated with genetic variability. Here, we use chronoamperometry to investigate variations in serotonin transport in primary lymphocytes associated with the rhesus serotonin transporter gene-linked polymorphism (rh5-HTTLPR), a promoter polymorphism whose orthologues occur only in higher order primates including humans. Serotonin clearance by lymphocytes is Na+-dependent and inhibited by the serotonin-selective reuptake inhibitor paroxetine (Paxil), indicative of active uptake by serotonin transporters. Moreover, reductions in serotonin uptake rates are evident in lymphocytes from monkeys with one or two copies of the short ‘s’ allele of the rh5-HTTLPR (s/s < s/l < l/l). These findings illustrate that rh5-HTTLPR-related alterations in serotonin uptake are present during adulthood in peripheral blood cells natively expressing serotonin transporters. Moreover, they suggest that lymphocytes can be used as peripheral biomarkers for investigating genetic or pharmacologic alterations in serotonin transporter function. Use of boron-doped diamond microelectrodes for measuring serotonin uptake, in contrast to carbon fiber microelectrodes used previously in the brain, enabled these high-sensitivity and high-resolution measurements. Boron-doped diamond microelectrodes show excellent signal-to-noise and signal-to-background ratios due mainly to low background currents and are highly resistant to fouling when exposed to lymphocytes or high concentrations of serotonin. PMID:20352073

  1. An association, in adult Japanese, between the occurrence of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of "simple" chromosomal damage among the lymphocytes of persons exhibiting these rogue cells.

    PubMed Central

    Neel, J V

    1998-01-01

    Data from a previous study of the cytogenetic effects, in cultured lymphocytes, of exposure to the atomic bomb in Hiroshima have been reanalyzed to determine the relationship between the occurrence of "rogue" cells in an individual and the frequency of "simple" chromosomal damage in the nonrogue cells of the same individual. Rogue cells are cells with complex chromosomal damage, currently believed to be a manifestation of the activity of a human polyoma virus termed "JC." Among a total of 1,835 persons examined, there were 45 exhibiting rogue cells. A total of 179,599 cells were scored for simple chromosomal damage. In both the exposed and the control populations, there was an absolute increase of approximately 1.5% in the frequency of simple chromosomal damage in the nonrogue cells of those exhibiting rogue cells, when compared with the frequencies observed in those not exhibiting rogue cells, which is a statistically significant difference. It is argued that this phenomenon, occurring not only in lymphocytes but possibly also in other cells/tissues, may play a contributory role in the origin of malignancies characterized by clonal chromosome abnormalities. Unexpectedly, among those exhibiting rogue cells, there was a disproportionately greater representation of persons who had received relatively high radiation exposures from the bomb. The reason for this is unclear, but it is tempting to relate the finding to some lingering effect of the exposure (or the circumstances surrounding the exposure) on immunocompetence. PMID:9683586

  2. B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

    PubMed

    Oballah, Peter; Flach, Britta; Eller, Leigh A; Eller, Michael A; Ouma, Benson; de Souza, Mark; Kibuuka, Hannah N; Wabwire-Mangen, Fred; Brown, Bruce K; Michael, Nelson L; Robb, Merlin L; Montefiori, David; Polonis, Victoria R

    2011-01-01

    To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.

  3. T-cell receptor gamma--delta lymphocytes and Eimeria vermiformis infection.

    PubMed Central

    Rose, M E; Hesketh, P; Rothwell, L; Gramzinski, R A

    1996-01-01

    The role of T-cell receptor gamma--delta T lymphocytes in coccidiosis was examined by determining the course of infection with Eimeria vermiformis in BALB/c mice depleted of gamma--delta lymphocytes by treatment with GL3 monoclonal antibody. The replication of the parasite in primary infections was not greatly, or consistently, affected by this treatment, and there was no correlation between the extent of depletion of small intestinal intraepithelial lymphocytes and the number of oocysts produced. The resistance of immunized mice to challenge was not compromised by depletion of intraintestinal epithelial lymphocytes when their depletion was effected at the time of primary infection and/or administration of the challenge inoculum. Thus, T-cell receptor gamma--delta T lymphocytes do not appear to be crucial to the establishment, or the control, of primary infection with E. vermiformis and are not principal mediators of the solid immunity to challenge that this infection induces. PMID:8890252

  4. Interactions between B lymphocyte subpopulations. Augmentation of the responses of resting B lymphocytes by activated B lymphocytes.

    PubMed

    Uher, F; Dickler, H B

    1988-03-01

    Mouse B lymphocytes were fractionated from normal T lymphocyte-depleted spleen cell populations using discontinuous percoll gradients and were stimulated with rabbit F(ab')2 anti-mouse mu-specific antibodies (anti-mu) plus the supernatant of Con A-stimulated rat spleen cells (SN) as a source of lymphokines. The responses of small (mean volume 120 mu 3), dense (greater than 1.087 specific gravity), resting (least spontaneous thymidine incorporation) B lymphocytes were augmented by irradiated (4000 rad), larger (mean volume greater than 170 mu 3), less dense (less than 1.081 specific gravity), activated (greater spontaneous thymidine incorporation) B lymphocytes. Proliferation was augmented 2- to 4-fold and polyclonal antibody-forming cell responses three- to sixfold. Maximal augmentation of the responses of 5 X 10(4) resting B cells was obtained with 10(4) activated B cells. Augmenting activity was specific for activated B lymphocytes in that responses were not augmented by irradiated thymocytes, T lymphoblasts, macrophages, or additional supernatant. B lymphocytes activated in vitro by LPS or anti-mu also had augmenting activity. Augmentation of responses was maximal only when activated B lymphocytes were added simultaneously with anti-mu. The interaction between activated and resting B lymphocytes did not appear to be genetically restricted. Interestingly, the augmenting activity of activated B cells could be reconstituted by a combination of supernatant and cell membranes from these cells but not by either alone, suggesting that two components are required, one soluble and the other membrane-bound. Thus, a functional interaction has been demonstrated between B lymphocyte subpopulations which differ in their state of activation, and this interaction appears to involve a novel mechanism of action.

  5. Anti-NGF monoclonal antibody muMab 911 does not deplete neurons in the superior cervical ganglia of young or old adult rats.

    PubMed

    Marcek, John; Okerberg, Carlin; Liu, Chang-Ning; Potter, David; Butler, Paul; Boucher, Magalie; Zorbas, Mark; Mouton, Peter; Nyengaard, Jens R; Somps, Chris

    2016-10-01

    Nerve growth factor (NGF) blocking therapies are an emerging and effective approach to pain management. However, concerns about the potential for adverse effects on the structure and function of the peripheral nervous system have slowed their development. Early studies using NGF antisera in adult rats reported effects on the size and number of neurons in the sympathetic chain ganglia. In the work described here, both young adult (6-8 week) and fully mature (7-8 month) rats were treated with muMab 911, a selective, murine, anti-NGF monoclonal antibody, to determine if systemic exposures to pharmacologically active levels of antibody for 1 month cause loss of neurons in the sympathetic superior cervical ganglia (SCG). State-of-the-art, unbiased stereology performed by two independent laboratories was used to determine the effects of muMab 911 on SCG neuronal number and size, as well as ganglion size. Following muMab 911 treatment, non-statistically significant trends toward smaller ganglia, and smaller and fewer neurons, were seen when routine, nonspecific stains were used in stereologic assessments. However, when noradrenergic neurons were identified using tyrosine hydroxylase (TH) immunoreactivity, trends toward fewer neurons observed with routine stains were not apparent. The only statistically significant effects detected were lower SCG weights in muMab 911-treated rats, and a smaller volume of TH immunoreactivity in neurons from younger rats treated with muMab 911. These results indicate that therapeutically relevant exposures to the anti-NGF monoclonal antibody muMab 911 for 1 month have no effect on neuron numbers within the SCG from young or old adult rats.

  6. Lymphocyte Surface Markers and Serum Immunoglobulins in Persons with Down's Syndrome.

    ERIC Educational Resources Information Center

    And Others; Hann, Hie-Won L.

    1979-01-01

    Distributions of the serum immunoglobulins (IgM), of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. (Author)

  7. Comparisons of CVID and IgGSD: referring physicians, autoimmune conditions, pneumovax reactivity, immunoglobulin levels, blood lymphocyte subsets, and HLA-A and -B typing in 432 adult index patients.

    PubMed

    Barton, James C; Bertoli, Luigi F; Barton, J Clayborn

    2014-01-01

    Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren's syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)).

  8. Identification of Two New HLA-A*1101-Restricted Tax Epitopes Recognized by Cytotoxic T Lymphocytes in an Adult T-Cell Leukemia Patient after Hematopoietic Stem Cell Transplantation

    PubMed Central

    Harashima, Nanae; Tanosaki, Ryuji; Shimizu, Yukiko; Kurihara, Kiyoshi; Masuda, Takao; Okamura, Jun; Kannagi, Mari

    2005-01-01

    We previously reported that Tax-specific CD8+ cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo. PMID:16014972

  9. Identification of two new HLA-A*1101-restricted tax epitopes recognized by cytotoxic T lymphocytes in an adult T-cell leukemia patient after hematopoietic stem cell transplantation.

    PubMed

    Harashima, Nanae; Tanosaki, Ryuji; Shimizu, Yukiko; Kurihara, Kiyoshi; Masuda, Takao; Okamura, Jun; Kannagi, Mari

    2005-08-01

    We previously reported that Tax-specific CD8(+) cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo.

  10. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  11. Water Depletion Threatens Agriculture

    NASA Astrophysics Data System (ADS)

    Brauman, K. A.; Richter, B. D.; Postel, S.; Floerke, M.; Malsy, M.

    2014-12-01

    Irrigated agriculture is the human activity that has by far the largest impact on water, constituting 85% of global water consumption and 67% of global water withdrawals. Much of this water use occurs in places where water depletion, the ratio of water consumption to water availability, exceeds 75% for at least one month of the year. Although only 17% of global watershed area experiences depletion at this level or more, nearly 30% of total cropland and 60% of irrigated cropland are found in these depleted watersheds. Staple crops are particularly at risk, with 75% of global irrigated wheat production and 65% of irrigated maize production found in watersheds that are at least seasonally depleted. Of importance to textile production, 75% of cotton production occurs in the same watersheds. For crop production in depleted watersheds, we find that one half to two-thirds of production occurs in watersheds that have not just seasonal but annual water shortages, suggesting that re-distributing water supply over the course of the year cannot be an effective solution to shortage. We explore the degree to which irrigated production in depleted watersheds reflects limitations in supply, a byproduct of the need for irrigation in perennially or seasonally dry landscapes, and identify heavy irrigation consumption that leads to watershed depletion in more humid climates. For watersheds that are not depleted, we evaluate the potential impact of an increase in irrigated production. Finally, we evaluate the benefits of irrigated agriculture in depleted and non-depleted watersheds, quantifying the fraction of irrigated production going to food production, animal feed, and biofuels.

  12. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

    PubMed Central

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  13. SGN-30 and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-02-10

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  14. Halo Star Lithium Depletion

    SciTech Connect

    Pinsonneault, M. H.; Walker, T. P.; Steigman, G.; Narayanan, Vijay K.

    1999-12-10

    The depletion of lithium during the pre-main-sequence and main-sequence phases of stellar evolution plays a crucial role in the comparison of the predictions of big bang nucleosynthesis with the abundances observed in halo stars. Previous work has indicated a wide range of possible depletion factors, ranging from minimal in standard (nonrotating) stellar models to as much as an order of magnitude in models that include rotational mixing. Recent progress in the study of the angular momentum evolution of low-mass stars permits the construction of theoretical models capable of reproducing the angular momentum evolution of low-mass open cluster stars. The distribution of initial angular momenta can be inferred from stellar rotation data in young open clusters. In this paper we report on the application of these models to the study of lithium depletion in main-sequence halo stars. A range of initial angular momenta produces a range of lithium depletion factors on the main sequence. Using the distribution of initial conditions inferred from young open clusters leads to a well-defined halo lithium plateau with modest scatter and a small population of outliers. The mass-dependent angular momentum loss law inferred from open cluster studies produces a nearly flat plateau, unlike previous models that exhibited a downward curvature for hotter temperatures in the 7Li-Teff plane. The overall depletion factor for the plateau stars is sensitive primarily to the solar initial angular momentum used in the calibration for the mixing diffusion coefficients. Uncertainties remain in the treatment of the internal angular momentum transport in the models, and the potential impact of these uncertainties on our results is discussed. The 6Li/7Li depletion ratio is also examined. We find that the dispersion in the plateau and the 6Li/7Li depletion ratio scale with the absolute 7Li depletion in the plateau, and we use observational data to set bounds on the 7Li depletion in main-sequence halo

  15. The inhibition of dopamine synthesis in fetuses changes the pattern of T-lymphocyte maturation in the thymus of adult rats.

    PubMed

    Lifantseva, N V; Koneeva, Ts O; Voronova, S N; Zakharova, L A; Melnikova, V I

    2016-09-01

    The mRNA for dopamine receptors of type D1, D3, D5, but not type D2, was detected in the thymus of rats starting from day 16 of embryonic development (E16). Dopamine at concentrations of 10(-8)-10(‒6) M inhibited fetus thymocyte response to mitogen, confirming the functionality of the receptors and the possibility of a direct effect of dopamine on the developing thymus. Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes. The presence and functional activity of dopamine receptors in the fetal thymus indicates its ability to influence the development of the immune system of rats during ontogeny.

  16. Battery depletion monitor

    SciTech Connect

    Lee, Y.S.

    1982-01-26

    A cmos inverter is used to compare pacemaker battery voltage to a referenced voltage. When the reference voltage exceeds the measured battery voltage, the inverter changes state to indicate battery depletion.

  17. Addressing Ozone Layer Depletion

    EPA Pesticide Factsheets

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  18. Depleted Uranium: Technical Brief

    EPA Pesticide Factsheets

    This technical brief provides accepted data and references to additional sources for radiological and chemical characteristics, health risks and references for both the monitoring and measurement, and applicable treatment techniques for depleted uranium.

  19. Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-05-07

    Adult Favorable Prognosis Hodgkin Lymphoma; Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Adult Unfavorable Prognosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  20. Apolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-15

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

  1. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    PubMed

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-02-22

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  2. Lymphocyte Functions in Microgravity

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    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.

  3. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; 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; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. HIV-1 envelope-dependent restriction of CXCR4-using viruses in child but not adult untransformed CD4+ T-lymphocyte lines.

    PubMed

    Mariani, Samanta A; Brigida, Immacolata; Kajaste-Rudnitski, Anna; Ghezzi, Silvia; Rocchi, Alessia; Plebani, Anna; Vicenzi, Elisa; Aiuti, Alessandro; Poli, Guido

    2012-03-01

    Phytohemagglutin-stimulated child and adult leukocytes equally supported CCR5-dependent (R5) and CXCR4-dependent (X4) HIV-1 replication. In contrast, when phytohemagglutin-stimulated leukocytes from either healthy or congenitally immunodeficient children were cultured on feeder cells, they well supported R5, but not X4 HIV-1 replication, whereas both viruses equally spread in adult cells maintained in similar conditions. Both child and adult cells showed similar levels of proliferation and surface expression of CD4, CCR5, CXCR4, CD25, CD69, and HLA-DR. Lack of X4 HIV-1 replication in child versus adult cells was not caused by a differential expression of several known HIV-1 restriction factors. Similar levels of HIV DNA synthesis occurred in child cells infected with R5 and X4 viruses up to 48 hours after infection when R5 HIV-1 showed a significantly superior capacity to spread in culture than X4 virus. Cultured child cells well supported single round vescicular stomatitis virus-G pseudotyped virus replication, whereas superinfection of R5-infected cells with X4 HIV-1 (or vice versa) rescued the replication of this latter virus. Thus, child cells exposed to feeder cell culture represent a novel model system in which the superior capacity of R5 versus X4 viruses to spread can be investigated in primary, untransformed CD4(+) cells.

  5. SnapShot: chronic lymphocytic leukemia.

    PubMed

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

    2014-11-10

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

  6. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. FATE OF THE LYMPHOCYTE

    PubMed Central

    Bunting, C. H.; Huston, John

    1921-01-01

    Although the count of circulating lymphocytes in the blood stream remains constant, more lymphocytes enter the blood from the thoracic duct during 24 hours than are present in the blood at any one time. This excess of lymphocytes is not destroyed in the blood stream. The cells migrate from the blood vessels into the mucous membranes and through them to their surface. This occurs chiefly in the gastrointestinal tract, and it is apparently in the mucosa and especially within the intestinal lumen that the function of the lymphocyte is normally performed. PMID:19868519

  8. Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-10-06

    Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  9. Modulation of Haemonchus contortus infection by depletion of γδ(+) T cells in parasite resistant Canaria Hair Breed sheep.

    PubMed

    Hernández, Julia N; Meeusen, Els; Stear, Michael; Rodríguez, Francisco; Piedrafita, David; González, Jorge F

    2017-04-15

    Canaria Hair Breed (CHB) sheep display resistance against the adult stage of the nematode, Haemonchus contortus. Previous studies have suggested significant correlations between γδ(+) T lymphocytes and fecundity of female adult worms, suggesting a novel role in immune modulation by these cells. The largest proportion of γδ(+) T lymphocytes in sheep are the subpopulation of γδ(+)/WC1(+) T cells. The aim of this study was to evaluate the effect of γδ(+)⁄WC1(+) T cell depletion via infusion of anti-γδ/WC1 monoclonal antibody (mAb) on the subsequent immune response of CHB sheep infected with H. contortus. Significantly lower γδ(+) T cell levels in both peripheral blood and in the basal layers of the abomasal tissue resulted following anti-γδ/WC1 mAb infusion of CHB sheep compared to control animals. Worms recovered from the anti-γδ/WC1 mAb treated CHB sheep had significantly longer female worms with correspondingly more eggs in utero than the saline control group. Significant correlations between eosinophils and worm length and fecundity were no longer apparent in the anti-γδ/WC1 mAb treated CHB sheep. These results support the notion that γδ(+) T cells in CHB sheep play a critical role in fecundity regulation (length and eggs in utero) of H. contortus adult female worms, and highlights a new mechanism of modulation by this lymphocyte population, possibly involving eosinophil activation.

  10. Lymphocyte migration in murine malaria during the primary patent parasitaemia of Plasmodium chabaudi infections.

    PubMed Central

    Kumararatne, D S; Phillips, R S; Sinclair, D; Parrott, M V; Forrester, J B

    1987-01-01

    Inoculation of adult C57/BC mice with 10(6) red cells infected with Plasmodium chabaudi induces an acute primary parasitaemia peaking around the 8th or 9th day and lasting 10-14 days. Concomitantly, the spleen enlarges to reach 6-7 times its normal weight by the 11th day. The major component of this increase is between day 9 and 11, due primarily to an increase in erythropoietic cells in the red pulp. Although initially the white pulp increases in size, by day 11 it shows partial lymphocyte depletion which coincides with the occurrence of massive absolute lymphocytosis in the peripheral blood. 3H-Thymidine labelling in vivo suggests that this lymphocytosis is not due to lymphocytopoiesis. Collectively, these findings suggest a redistribution of lymphocytes. Lymphocyte migration was investigated around peak parasitaemia, using enriched populations of T and B cells labelled with 51Cr. The traffic patterns of these cells were followed over 36 h. These studies show decreased uptake (or decreased retention) of T and B cells by spleens of infected mice. Concomitantly, there is increased retention of T and B cells in the liver and lungs of infected mice, suggesting a complex redistribution of these cells. Lymphocyte migration to lymph nodes was unimpaired in these animals. Similar changes in T and B cell migration do not occur in Babesia microti infections in C57/BL mice. We relate our findings to histological and histochemical changes in the liver and spleen of malarious mice and discuss the significance of these findings to immunosuppression in malaria and to the development of parasiticidal immunity. Images Fig. 3a Fig. 3b Fig. 3c Fig. 3d Fig. 3 PMID:3498567

  11. Cholesterol depletion induces autophagy

    SciTech Connect

    Cheng, Jinglei; Ohsaki, Yuki; Tauchi-Sato, Kumi; Fujita, Akikazu; Fujimoto, Toyoshi . E-mail: tfujimot@med.nagoya-u.ac.jp

    2006-12-08

    Autophagy is a mechanism to digest cells' own components, and its importance in many physiological and pathological processes is being recognized. But the molecular mechanism that regulates autophagy is not understood in detail. In the present study, we found that cholesterol depletion induces macroautophagy. The cellular cholesterol in human fibroblasts was depleted either acutely using 5 mM methyl-{beta}-cyclodextrin or 10-20 {mu}g/ml nystatin for 1 h, or metabolically by 20 {mu}M mevastatin and 200 {mu}M mevalonolactone along with 10% lipoprotein-deficient serum for 2-3 days. By any of these protocols, marked increase of LC3-II was detected by immunoblotting and by immunofluorescence microscopy, and the increase was more extensive than that caused by amino acid starvation, i.e., incubation in Hanks' solution for several hours. The induction of autophagic vacuoles by cholesterol depletion was also observed in other cell types, and the LC3-positive membranes were often seen as long tubules, >50 {mu}m in length. The increase of LC3-II by methyl-{beta}-cyclodextrin was suppressed by phosphatidylinositol 3-kinase inhibitors and was accompanied by dephosphorylation of mammalian target of rapamycin. By electron microscopy, autophagic vacuoles induced by cholesterol depletion were indistinguishable from those seen after amino acid starvation. These results demonstrate that a decrease in cholesterol activates autophagy by a phosphatidylinositol 3-kinase-dependent mechanism.

  12. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  13. Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-12-26

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

  14. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma.

    PubMed

    Yamaguchi, Takahiro; Ohshima, Koichi; Tsuchiya, Takeshi; Suehuji, Hiroaki; Karube, Kennosuke; Nakayama, Juichiro; Suzumiya, Junji; Yoshino, Tadashi; Kikuchi, Masahiro

    2003-01-01

    Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1). In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial. In the present study, to discriminate MF and cutaneous lesion of ATLL using immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not in any MF cases. OX40 was expressed in the large transformed cell population in both disorders. These findings suggest that CLA and ST2 could be potentially useful immunohistochemical markers for discrimination of mycosis fungoides and cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker for the histopathological progression of both disorders.

  15. DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults.

    PubMed

    Gorse, Geoffrey J; Newman, Mark J; deCamp, Allan; Hay, Christine Mhorag; De Rosa, Stephen C; Noonan, Elizabeth; Livingston, Brian D; Fuchs, Jonathan D; Kalams, Spyros A; Cassis-Ghavami, Farah L

    2012-05-01

    We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.

  16. Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission.

    PubMed

    Nishiwaki, Satoshi; Inamoto, Yoshihiro; Sakamaki, Hisashi; Kurokawa, Mineo; Iida, Hiroatsu; Ogawa, Hiroyasu; Fukuda, Takahiro; Ozawa, Yukiyasu; Kobayashi, Naoki; Kasai, Masanobu; Mori, Takehiko; Iwato, Koji; Yoshida, Takashi; Onizuka, Makoto; Kawa, Keisei; Morishima, Yasuo; Suzuki, Ritsuro; Atsuta, Yoshiko; Miyamura, Koichi

    2010-11-18

    To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph(-) ALL in CR1 could be improved.

  17. T lymphocyte roles during Eimeria acervulina and Eimeria tenella infections.

    PubMed

    Trout, J M; Lillehoj, H S

    1996-09-01

    This study evaluated the effects of selective depletion of T lymphocytes on Eimeria infections in chickens. Cell depletions were initiated in day- or week-old Hyline SC strain chickens using intra-peritoneal injections of monoclonal antibodies to CD4, CD8, or T cell receptor (TCR) alpha/beta. Control chickens received injections of irrelevant monoclonal antibody or phosphate buffered saline (PBS). Following the establishment of cell depletion, chickens were infected orally with E. acervulina or E. tenella, 1 x 10(4) oocysts for primary infections and 2 x 10(5) oocysts for secondary infections. Chickens treated with anti CD4 monoclonal antibody produced significantly more oocysts than controls following primary E. tenella but not E. acervulina infections. Development of resistance to challenge infection was unaffected. These results suggest that CD4+ lymphocytes are important in controlling primary infection with E. tenella. Chickens treated with anti-CD8 or anti-TCR alpha/beta monoclonal antibodies produced significantly fewer oocysts than controls following primary infection but significantly more oocysts than controls following secondary infection with both E. tenella and E. acervulina. Additionally, anti-CD8 treatment abrogated resistance to challenge infection. CD8-depleted chickens may exhibit decreased oocyst production following primary infection due to a lack of CD8+ lymphocytes to serve as transporting cells for sporozoites. The abrogation of resistance to secondary infection in CD8- and TCR alpha/beta-depleted chickens suggests that these cells are necessary for the development of protective immunity to coccidia.

  18. In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis

    SciTech Connect

    Phillips, S.M.; Linette, G.P.; Doughty, B.L.; Byram, J.E.; Von Lichtenberg, F.

    1987-08-01

    These studies assessed the roles of subpopulations of T lymphocytes in inducing and modulating resistance to schistosomiasis and thereby influencing subsequent morbidity. C57BL/6 mice were depleted in vivo of Lyt-1+, Lyt-2+, and L3T4+ cells by the daily administration of monoclonal antibodies. The development of protective immunity, induced by exposure to irradiated Schistosoma mansoni cercariae as expressed in depleted animals, was compared to that demonstrated in undepleted, normal, and congenitally athymic C57BL/6 mice. The development of morbidity was determined by spleen weight, portal pressure and reticuloendothelial system activity. The results indicated that depletion of specific subpopulations of T lymphocytes minimally affected the primary development of parasites; however, depletion strongly influenced the development of resistance to the parasite and subsequent morbidity due to infection. Depletion of T lymphocytes by anti-Lyt-1+ or anti-L3T4+ antibody decreased the development of resistance, antibody and delayed-type hypersensitivity directed against schistosome antigens. Morbidity due to disease was increased. Depletion of Lyt-2+ cells produced opposite changes with augmented resistance and reduced morbidity. Congenitally athymic mice developed minimal resistance and morbidity. Moreover, resistance was inversely related to the morbidity shown by a given animal. These studies indicate that the development of protective immunity to S. mansoni cercariae is regulated by discrete subpopulations of T lymphocytes. The feasibility of decreasing morbidity by increasing specific immunologically mediated resistance is suggested.

  19. Lymphocyte emperipolesis revisited

    PubMed Central

    Sandilands, G. P.; Reid, Fiona M.; Gray, Kathleen G.; Anderson, J. R.

    1978-01-01

    A surprisingly high proportion of antibody (IgG) sensitized Chang liver cells apparently contained one or more intracytoplasmic human peripheral blood lymphocytes following a period of contact at 37°. Since various technical factors were found to influence this phenomenon of lymphocyte `emperipolesis', optimum conditions were selected for use in a standard quantitative in vitro assay. Lymphocytes from normal individuals varied considerably in their ability to participate in emperipolesis; an observation which suggested that a particular lymphocyte subpopulation may be involved. Preliminary characterization of emperipoletic cells indicated that they are Fc receptor bearing, non-T lymphocytes. The significance of these findings in relation to immune mechanisms is discussed. ImagesFigure 1Figure 2 PMID:312253

  20. Evaluation of spontaneous DNA damage in lymphocytes of healthy adult individuals from high-level natural radiation areas of Kerala in India.

    PubMed

    Kumar, P R Vivek; Cheriyan, V D; Seshadri, M

    2012-05-01

    Inhabitants of the high-level natural radiation areas (>1 mSv year(-1)) of Kerala in southwest India were evaluated for basal damage (spontaneous DNA strand breaks and alkali-labile sites) by the alkaline comet assay and oxidative DNA damage (ENDO III- and hOGG1-sensitive sites) by the enzyme-modified comet assay. Of the 67 adult male subjects studied, 45 were from high-level natural radiation areas and 22 subjects were from a nearby normal-level natural radiation area (≤1 mSv year(-1)). Basal damage due to the age and residential area (normal-level natural radiation area/high-level natural radiation areas) of the donors showed significant interaction (P < 0.001) when all subjects were analyzed using a general linear model (GLM). In subgroup analysis, basal damage increased with age in subjects from the normal-level natural radiation area (P = 0.02), while a significant negative correlation (P = 0.002) was observed in subjects from high-level natural radiation areas. Further, basal damage in elderly subjects from high-level natural radiation areas was significantly (P < 0.001) lower compared to the subjects from the normal-level natural radiation area. Oxidative DNA damage was not influenced by age, smoking habit or residential area in the entire sample. However, in a subgroup analysis, hOGG1-sensitive sites showed a significant increase with age in subjects from high-level natural radiation areas (P = 0.005). ENDO III-sensitive sites increased with natural radiation exposure in subjects from high-level natural radiation areas (P = 0.02), but when stratified according to smoking, a significant increase was observed only in smokers (P = 0.01). To the best of our knowledge, this is the first study on basal and oxidative DNA damage in healthy adults of this population. However, our findings need more validation in a larger study population.

  1. A majority of Ig H chain cDNA of normal human adult blood lymphocytes resembles cDNA for fetal Ig and natural autoantibodies

    SciTech Connect

    Huang, C.; Stollar, B.D. )

    1993-11-15

    Certain Ig V[sub H] gene segments, with few or no mutations, recur frequently in natural autoantibodies, fetal antibodies, and products of B cell tumors. The goal of this study was to determine whether similar Ig gene segment usage occurs in normal human adult PBL. Extending previous analyses, 105 randomly picked H chain V region clones of representative cDNA libraries from PBL were sequenced. Clones were from: IgM and IgG libraries from one RNA sample of a normal adult; a second IgM library from the same subject 11 mo later; and one IgM library from a second subject. Although some clones had clear evidence of mutation, 48 of 77 IgM clones (62%) shared 99% or more identity with known germline V[sub H] segments, and most of these had no mutations in the CDR3 portion of the J[sub H] segment. Certain V[sub H] gene segments, expressed in autoantibodies and fetal antibodies, occurred at high frequency in these libraries. Fourteen of the clones with 99% identity to known V[sub H] segments had CDR3 segments identical to portions of known germline D[sub H] gene sequences; two such clones had no N nucleotides at the V[sub H] D[sub H] or D[sub H]J[sub H] junctions. IgG-encoding sequences had more mutations than IgM-encoding sequences. J[sub H] and D[sub H] usage was not random. The circulating B cell population may represent a distinct compartment, with a large proportion of cells similar to those of the fetal and natural autoantibody repertoire. Polyreactive Ig products of these circulating cells may serve a screening function, binding and delivering diverse Ag to secondary lymphoid tissues where more highly selective antibodies are formed to foreign or Self-Ag. 40 refs., 2 figs., 6 tabs.

  2. Effects of exogenous vitamin A, C, E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects.

    PubMed

    Bouamama, Samia; Merzouk, Hafida; Medjdoub, Amel; Merzouk-Saidi, Amel; Merzouk, Sid Ahmed

    2017-01-23

    Aging is an inevitable biological event that is associated with immune alterations. These alterations are related to increased cellular oxidative stress and micronutrient deficiency. Antioxidant supplementation could improve these age-related abnormalities. The aim of this study was to determine in vitro effects of vitamin A, vitamin C, vitamin E, and NADH on T cell proliferation, cytokine release, and cell redox status in the elderly compared to young adults. Peripheral blood lymphocytes were isolated using a density gradient of Histopaque. They were cultured in vitro and stimulated with concanavalin A in the presence or absence of vitamins. Cell proliferation was determined by conducting MTT assays, and based on interleukin-2 and interleukin -4 secretions. Cell oxidant/antioxidant balance was assessed by assaying glutathione (GSH), malondialdehyde, carbonyl protein levels, and catalase activity. The present study demonstrated that T-lymphocyte proliferation was decreased with aging and was associated with cytokine secretion alterations, GSH depletion, and intracellular oxidative stress. In the elderly, vitamin C, vitamin E, and NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress, whereas vitamin A did not affect cell proliferation or cell redox status. In conclusion, vitamin C, vitamin E, and NADH supplementation improved T-lymphocytes response in the elderly, and could contribute to the prevention of age-related immune alterations. Consumption of food items containing these vitamins is recommended, and further investigation is necessary to evaluate the effect of vitamin supplementation in vivo.

  3. Human podocyte depletion in association with older age and hypertension.

    PubMed

    Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

    2016-04-01

    Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease.

  4. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-12-08

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  5. Supportive Care for Chronic Lymphocytic Leukemia

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Supportive Care for Chronic Lymphocytic Leukemia Supportive care for chronic lymphocytic leukemia (CLL) is ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  6. A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    ClinicalTrials.gov

    2017-01-24

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  7. Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    ClinicalTrials.gov

    2017-02-24

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  8. Tank depletion flow controller

    DOEpatents

    Georgeson, Melvin A.

    1976-10-26

    A flow control system includes two bubbler tubes installed at different levels within a tank containing such as radioactive liquid. As the tank is depleted, a differential pressure transmitter monitors pressure differences imparted by the two bubbler tubes at a remote, shielded location during uniform time intervals. At the end of each uniform interval, balance pots containing a dense liquid are valved together to equalize the pressures. The resulting sawtooth-shaped signal generated by the differential pressure transmitter is compared with a second sawtooth signal representing the desired flow rate during each time interval. Variations in the two signals are employed by a control instrument to regulate flow rate.

  9. Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

    NASA Astrophysics Data System (ADS)

    Shi, Yufang

    Space radiation, composed of high-energy charged nuclei (HZE particles) and protons, has been previously shown to severely impact immune homeostasis in mice. To determine the molecular mechanisms that mediate acute lymphocyte depletion following exposure to HZE particle radiation mice were exposed to particle radiation beams at Brookhaven National Laboratory. We found that mice given whole body 5 6Fe particle irradiation (1GeV /n) had dose-dependent losses in total lymphocyte numbers in the spleen and thymus (using 200, 100 and 50 cGy), with thymocytes being more sensitive than splenocytes. All phenotypic subsets were reduced in number. In general, T cells and B cells were equally sensitive, while CD8+ T cells were more senstive than CD4+ T cells. In the thymus, immature CD4+CD8+ double-positive thymocytes were exquisitely sensitive to radiation-induced losses, single-positive CD4 or CD8 cells were less sensitive, and the least mature double negative cells were resistant. Irradiation of mice deficient in genes encoding essential apoptosis-inducing proteins revealed that the mechanism of lymphocyte depletion is independent of Fas ligand and TRAIL (TNF-ralated apoptosis-inducing ligand), in contrast to γ-radiation-induced lymphocyte losses which require the Fas-FasL pathway. Using inhibitors in vitro, lymphocyte apoptosis induced by HZE particle radiation was found to be caspase dependent, and not involve nitric oxide or oxygen free radicals.

  10. Breast milk lymphocyte response to K1 antigen of Escherichia coli.

    PubMed Central

    Keller, M A; Turner, J L; Stratton, J A; Miller, M E

    1980-01-01

    Comparison milk and blood lymphocyte blastogenic responses to the K1 antigen of Escherichia coli and lipopolysaccharide (LPS) from E. coli O127,B8 were examined in 16 postpartum women by [3H]thymidine uptake. Rabbit hemolysincoated sheep erythrocyte monolayers were used to deplete macrophages from milk lymphocyte preparations and to enrich for T lymphocytes in order to make milk preparations more comparable to blood preparations. Response was defined as a stimulation index of greater than or equal to 2.0. There was no evidence of selective response to K1 antigen by milk lymphocytes, since both blood and milk lymphocytes responded in four women and neither blood nor milk lymphocytes responded in nine. Milk lymphocytes alone responded to K1 in one woman, whereas blood lymphocytes alone responded in two women. Additional nonpaired milk or blood cultures were available from three women. None of these responded to K1 antigen. Corresponding lymphocyte cultures were stimulated with LPS. A positive K1 response was always accompanied by an LPS response, and the LPS response correlated with the K1 response in 17 of 19 women. Stool cultures examined with an antiserum agar showed no correlation between the presence of K1 E. coli in the stool and milk or blood lymphocyte response to K1 antigen. In the system used here, no selectivity of response of breast milk lymphocytes to K1 antigen was noted. PMID:6991433

  11. Role of senescence marker p16 INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults.

    PubMed

    Pustavoitau, Aliaksei; Barodka, Viachaslau; Sharpless, Norman E; Torrice, Chad; Nyhan, Daniel; Berkowitz, Dan E; Shah, Ashish S; Bandeen Roche, Karen J; Walston, Jeremy D

    2016-02-01

    Adults older than 65 years undergo more than 120,000 coronary artery bypass (CAB) procedures each year in the United States. Chronological age alone, though commonly used in prediction models of outcomes after CAB, does not alone reflect variability in aging process; thus, the risk of complications in older adults. We performed a prospective study to evaluate a relationship between senescence marker p16(INK4a) expression in peripheral blood T-lymphocytes (p16 levels in PBTLs) with aging and with perioperative outcomes in older CAB patients. We included 55 patients age 55 and older, who underwent CAB in Johns Hopkins Hospital between September 1st, 2010 and March 25th, 2013. Demographic, clinical and laboratory data following outline of the Society of Thoracic Surgeons data collection form was collected, and p16 mRNA levels in PBTLs were measured using TaqMan® qRT-PCR. Associations between p16 mRNA levels in PBTLs with length of hospital stay, frailty status, p16 protein levels in the aortic and left internal mammary artery tissue, cerebral oxygen saturation, and augmentation index as a measure of vascular stiffness were measured using regression analyses. Length of hospital stay was the primary outcome of interest, and major organ morbidity, mortality, and discharge to a skilled nursing facility were secondary outcomes. In secondary analysis, we evaluated associations between p16 mRNA levels in PBTLs and interleukin-6 levels using regression analyses. Median age of enrolled patients was 63.5 years (range 56-81 years), they were predominantly male (74.55%), of Caucasian descent (85.45%). Median log2(p16 levels in PBTLs) were 4.71 (range 1.10-6.82). P16 levels in PBTLs were significantly associated with chronological age (mean difference 0.06 for each year increase in age, 95% CI 0.01-0.11) and interleukin 6 levels (mean difference 0.09 for each pg/ml increase in IL-6 levels, 95% CI 0.01-0.18). There were no significant associations with frailty status, augmentation

  12. Depletion of intense fields

    NASA Astrophysics Data System (ADS)

    Bulanov, S. S.; Seipt, D.; Heinzl, T.; Marklund, M.

    2017-03-01

    The problem of backreaction of quantum processes on the properties of the background field still remains on the list of outstanding questions of high intensity particle physics. Usually, photon emission by an electron or positron, photon decay into electron-positron pairs in strong electromagnetic fields, or electron-positron pair production by such fields are described in the framework of the external field approximation. It is assumed that the external field has infinite energy and is not affected by these processes. However, the above-mentioned processes have a multi-photon nature, i.e., they occur with the absorption of a significant number of field photons. As a result, the interaction of an intense electromagnetic field with either a highly charged electron bunch or a fast growing population of electrons, positrons, and gamma photons (as in the case of an electromagnetic cascade) may lead to a depletion of the field energy, thus making the external field approximation invalid. Taking the multi-photon Compton process as an example, we estimate the threshold of depletion and find it to become significant at field strengths (a0˜103) and electron bunch charge of about tens of nC.

  13. α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

    PubMed Central

    Bristow, Cynthia L.; Babayeva, Mariya A.; LaBrunda, Michelle; Mullen, Michael P.; Winston, Ronald

    2012-01-01

    Background The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLECS), it acts not as a proteinase, but as a receptor for α1proteinase inhibitor (α1PI, α1antitrypsin, SerpinA1). Binding of α1PI to HLECS forms a motogenic complex. We previously demonstrated that α1PI deficiency attends HIV-1 disease and that α1PI augmentation produces increased numbers of immunocompetent circulating CD4+ lymphocytes. Herein we investigated the mechanism underlying the α1PI deficiency that attends HIV-1 infection. Methods and Findings Active α1PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4+ lymphocytes were correlated with the combined factors α1PI, HLECS+ lymphocytes, and CXCR4+ lymphocytes (r2 = 0.91, p<0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/µl, CD4+ lymphocytes were correlated solely with active α1PI (r2 = 0.93, p<0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human α1PI. Chimpanzee α1PI differs from human α1PI by a single amino acid within the 3F5-binding epitope. Unlike human α1PI, chimpanzee α1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4+ lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-α1PI immune complexes correlated with decreased CD4+ lymphocytes in HIV-1 subjects. Conclusions This report identifies an autoimmune component of HIV-1 disease that can be overcome therapeutically. Importantly, results identify an achievable vaccine modification with the novel objective to protect against AIDS as opposed to the current objective to

  14. Serotonin and social norms: tryptophan depletion impairs social comparison and leads to resource depletion in a multiplayer harvesting game.

    PubMed

    Bilderbeck, Amy C; Brown, Gordon D A; Read, Judi; Woolrich, Mark; Cowen, Phillip J; Behrens, Tim E J; Rogers, Robert D

    2014-07-01

    How do people sustain resources for the benefit of individuals and communities and avoid the tragedy of the commons, in which shared resources become exhausted? In the present study, we examined the role of serotonin activity and social norms in the management of depletable resources. Healthy adults, alongside social partners, completed a multiplayer resource-dilemma game in which they repeatedly harvested from a partially replenishable monetary resource. Dietary tryptophan depletion, leading to reduced serotonin activity, was associated with aggressive harvesting strategies and disrupted use of the social norms given by distributions of other players' harvests. Tryptophan-depleted participants more frequently exhausted the resource completely and also accumulated fewer rewards than participants who were not tryptophan depleted. Our findings show that rank-based social comparisons are crucial to the management of depletable resources, and that serotonin mediates responses to social norms.

  15. Changes in phospholipid metabolism during B lymphocyte activation

    SciTech Connect

    Kriz, M.K.; Vitetta, E.S.; Sullivan, T.J.

    1986-07-15

    Phospholipid metabolism in murine B lymphocytes stimulated with anti-Ig bound to Sepharose has been examined. T cell-depleted splenic B lymphocytes cultured with Sepharose-coupled, affinity-purified goat anti-mouse Ig (GAMIg) increased the incorporation of /sup 32/PO/sub 4/ into phosphatidic acid and phosphatidylinositol within 3 hr and increased (/sup 3/H)-thymidine uptake at 48 hr. No increase in labeling was observed in phosphatidylethanolamine, phosphatidylcholine, or phosphatidylserine. Based on both negative and positive selection procedures, it was demonstrated that these responses occurred in B lymphocytes. In contrast to the thymidine uptake response did not require the presence of accessory cells or exogenous cytokines. The same selective changes in phospholipid metabolism were observed in neoplastic B lymphocytes (BCL/sub 1/) after treatment with Sepharose anti-..mu.., but not with Sepharose anti-Ia or Sepharose normal Ig. The dose-response relationships of /sup 32/PO/sub 4/ incorporation into phosphatidic acid and phosphatidylinositol and (/sup 3/H) thymidine uptake were nearly identical in BCL/sub 1/ cells. The results of these experiments indicate that interaction B lymphocytes with insolubilized anti-Ig results in prompt and selective changes in phospholipid metabolism that appear to be correlated with B lymphocyte proliferation.

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

    ClinicalTrials.gov

    2015-11-10

    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. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

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

  18. 12. VIEW OF DEPLETED URANIUM INGOT AND MOLDS. DEPLETED URANIUM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. VIEW OF DEPLETED URANIUM INGOT AND MOLDS. DEPLETED URANIUM CASTING OPERATIONS CEASED IN 1988. (11/14/57) - Rocky Flats Plant, Non-Nuclear Production Facility, South of Cottonwood Avenue, west of Seventh Avenue & east of Building 460, Golden, Jefferson County, CO

  19. Depleted Uranium in Repositories

    SciTech Connect

    Haire, M.J.; Croff, A.G.

    1997-12-31

    For uranium to be useful in most fission nuclear reactors, it must be enriched (i.e. the concentration of the fissile isotope 235U must be increased). Therefore, depleted uranium (DU)-uranium which has less than naturally occurring concentrations of 235U-is a co-product of the enrichment process. Four to six tons of DU exist for every ton of fresh light water reactor fuel. There were 407,006 MgU 407,000 metric tons (t) of DU stored on U.S. Department of Energy (DOE) sites as of July 1993. If this DU were to be declared surplus, converted to a stable oxide form, and emplaced in a near surface disposal facility, the costs are estimated to be several billion dollars. However, the U.S. Nuclear Regulatory Commission has stated that near surface disposal of large quantities of DU tails is not appropriate. Thus, there is the possibility that disposition via disposal will be in a deep geological repository. One alternative that may significantly reduce the cost of DU disposition is to use it beneficially. In fact, DOE has begun the Beneficial Uses of DU Project to identify large scale uses of DU and to encourage its reuse. Several beneficial uses, many of which involve applications in the repository per se or in managing the wastes to go into the repository, are discussed in this report.

  20. Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

    NASA Technical Reports Server (NTRS)

    Rubin, A. L.

    1977-01-01

    Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

  1. Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2015-09-27

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  2. Ego depletion impairs implicit learning.

    PubMed

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  3. Stratospheric ozone depletion

    PubMed Central

    Rowland, F. Sherwood

    2006-01-01

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290–320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime—the ‘Antarctic ozone hole’. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules. PMID:16627294

  4. Stratospheric ozone depletion.

    PubMed

    Rowland, F Sherwood

    2006-05-29

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime-the 'Antarctic ozone hole'. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules.

  5. Testing fully depleted CCD

    NASA Astrophysics Data System (ADS)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  6. Transequatorial Propagation and Depletion Precursors

    NASA Astrophysics Data System (ADS)

    Miller, E. S.; Bust, G. S.; Kaeppler, S. R.; Frissell, N. A.; Paxton, L. J.

    2014-12-01

    The bottomside equatorial ionosphere in the afternoon and evening sector frequently evolves rapidly from smoothly stratified to violently unstable with large wedges of depleted plasma growing through to the topside on timescales of a few tens of minutes. These depletions have numerous practical impacts on radio propagation, including amplitude scintillation, field-aligned irregularity scatter, HF blackouts, and long-distance transequatorial propagation at frequencies above the MUF. Practical impacts notwithstanding, the pathways and conditions under which depletions form remain a topic of vigorous inquiry some 80 years after their first report. Structuring of the pre-sunset ionosphere---morphology of the equatorial anomalies and long-wavelength undulations of the isodensity contours on the bottomside---are likely to hold some clues to conditions that are conducive to depletion formation. The Conjugate Depletion Experiment is an upcoming transequatorial forward-scatter HF/VHF experiment to investigate pre-sunset undulations and their connection with depletion formation. We will present initial results from the Conjugate Depletion Experiment, as well as a companion analysis of a massive HF propagation data set.

  7. Neutrophil depletion delays wound repair in aged mice

    PubMed Central

    Nishio, Naomi; Okawa, Yayoi; Sakurai, Hidetoshi

    2008-01-01

    One of the most important clinical problems in caring for elderly patients is treatment of pressure ulcers. One component of normal wound healing is the generation of an inflammatory reaction, which is characterized by the sequential infiltration of neutrophils, macrophages and lymphocytes. Neutrophils migrate early in the wound healing process. In aged C57BL/6 mice, wound healing is relatively inefficient. We examined the effects of neutrophil numbers on wound healing in both young and aged mice. We found that the depletion of neutrophils by anti-Gr-1 antibody dramatically delayed wound healing in aged mice. The depletion of neutrophils in young mice had less effect on the kinetics of wound healing. Intravenous G-CSF injection increased the migration of neutrophils to the wound site. While the rate of wound repair did not change significantly in young mice following G-CSF injection, it increased significantly in old mice. PMID:19424869

  8. Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-27

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma

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

    PubMed

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

    1999-08-01

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

  10. Traffic and proliferative responses of recirculating lymphocytes in fetal calves.

    PubMed Central

    Hein, W R; Shelton, J N; Simpson-Morgan, M W; Morris, B

    1988-01-01

    The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 5.4 to 48.8 ml/hr. Lymphocyte output ranged from 4.4 x 10(6) cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 x 10(8) cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 x 10(8) cells and 2 x 10(10) cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. PMID:2971606

  11. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    ClinicalTrials.gov

    2017-02-21

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  12. Immunostimulation by cytomegalovirus (CMV): helper T cell-dependent activation of immunoglobulin production in vitro by lymphocytes from CMV-immune donors

    SciTech Connect

    Yachie, A.; Tosato, G.; Straus, S.E.; Blaese, R.M.

    1985-08-01

    Cytomegalovirus (CMV) is the cause of a number of different diseases ranging from self-limited benign infections in healthy adults to life threatening illnesses among immunocompromised hosts and newborns. Suppression of cell-mediated immunity is often found in cases of acute CMV infection, and in addition, the virus may also be a potent stimulant of lymphoid cells in vivo. The authors studied cellular proliferation and immunoglobulin (Ig) production induced by CMV to determine its effect on human lymphocytes in vitro. The CMV that was added to cultures of lymphocytes from CMV-seronegative donors failed to induce either significant cellular proliferation or Ig production. By contrast, CMV-stimulated cultures from CMV-seropositive donors induced both prominent cellular proliferation and Ig production. B cell differentiation into Ig-secreting cells required the presence of T cells, and this T cell help was sensitive to irradiation with 2000 rad and to treatment with cyclosporin A. When T cells were depleted of OKT4+ cells with monoclonal antibody and complement, the co-cultured B cells failed to produce Ig, whereas the depletion of OKT8+ cells had no effect on the Ig-secreting cell response. Inactivation of CMV before culture did not result in a reduction of either cellular proliferation or Ig production. Thus, infection of target cells is not required for in vitro lymphocyte activation by CMV. These results demonstrate that CMV is a potent activator of B cells inducing Ig production in vitro, and that this process requires the presence of virus-specific memory T cells.

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

    ClinicalTrials.gov

    2016-10-04

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

  14. Chronic Lymphocytic Leukemia and Other Lymphoproliferative Disorders.

    PubMed

    Wall, Sarah; Woyach, Jennifer A

    2016-02-01

    Chronic lymphocytic leukemia affects less than 1% of US adults but is the most common leukemia and primarily affects older patients. Non-Hodgkin lymphomas are the seventh most common cancers in the United States and also primarily affect older patients. In general, older patients should be treated differently than their younger, fitter counterparts. Fitness level and comorbidities should be taken into account when planning treatment. First-line treatment of most of these B-cell lymphoproliferative disorders consists of chemoimmunotherapy. In relapsed and refractory disease, there is a growing role for therapies targeting the B-cell receptor signaling pathway.

  15. Chronic administration of the metastin/kisspeptin analog KISS1-305 or the investigational agent TAK-448 suppresses hypothalamic pituitary gonadal function and depletes plasma testosterone in adult male rats.

    PubMed

    Matsui, Hisanori; Tanaka, Akira; Yokoyama, Kotaro; Takatsu, Yoshihiro; Ishikawa, Kaori; Asami, Taiji; Nishizawa, Naoki; Suzuki, Atsuko; Kumano, Satoshi; Terada, Michiko; Kusaka, Masami; Kitada, Chieko; Ohtaki, Tetsuya

    2012-11-01

    Metastin/kisspeptin, a hypothalamic peptide, plays a pivotal role in controlling GnRH neurons. Here we studied the effect of chronic sc administration of two kisspeptin analogs, KISS1-305 and TAK-448, on hypothalamic-pituitary-gonadal function in male rats in comparison with a GnRH analogue leuprolide or bilateral orchiectomy (ORX). The prototype polypeptide, KISS1-305 (1-4 nmol/h), caused substantial elevations of plasma LH and testosterone, followed by abrupt reductions of both hormone levels. Notably, testosterone levels were reduced to castrate levels within 3 d and remained depleted throughout the 4-wk dosing period, an effect that was faster and more pronounced than leuprolide (1 nmol/h) dosing. KISS1-305 also reduced genital organ weight more profoundly than leuprolide. In mechanistic studies, chronic KISS1-305 administration only transiently induced c-Fos expression in GnRH neurons, suggesting that GnRH-neural response was attenuated over time. Hypothalamic GnRH content was reduced to 10-20% of control at 3 wk without any changes in Gnrh mRNA expression. Dosing with the investigational peptide TAK-448 was also studied to extend our understanding of hypothalamic-pituitary functions. Similar to ORX, TAK-448 (0.1 nmol/h) depleted testosterone and decreased GnRH content by 4 wk. However, in contrast to ORX, TAK-448 decreased gonadotropin levels in pituitary and plasma samples, implying the suppression of GnRH pulses. These results suggest that chronic administration of kisspeptin analogs disrupts endogenous kisspeptin signals to suppress intrinsic GnRH pulses, perhaps by attenuating GnRH-neural response and inducing continuous GnRH leakage from the hypothalamus. The potential utility of kisspeptin analogs as novel agents to treat hormone-related diseases, including prostate cancer, is discussed.

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

    PubMed Central

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

    2015-01-01

    Alemtuzumab, an anti-CD52 T-cell and B-cell depleting monoclonal antibody, is established for induction therapy in renal transplantation (KTx). We herein provide a comparative analysis between alemtuzumab and basiliximab induction therapy and correlate lymphocyte depletion and recovery with the clinical course after KTx. This is a single center retrospective analysis of 225 patients/consecutive kidney transplantations treated with alemtuzumab for lymphocyte depletion and 205 recipients treated with basiliximab. Mean lymphocyte counts were 22.8 ± 9.41% before Tx and 2.61 ± 3.11% between week 1 and week 3 in the alemtuzumab group and 23.77 ± 10.42% before Tx and 13.92 ± 8.20% in the basiliximab group. Delayed graft function (DGF), cytomegalovirus (CMV) status, and recipient age showed a significant correlation with lymphocyte counts in the alemtuzumab group only. The outcome was read in reference to the velocity of lymphocyte recovery and in comparison to the control group. Lymphocyte counts early after transplantation, following alemtuzumab treatment, could be identified as a predictive factor for kidney function early after transplantation. A detailed analysis of phenotype and function of lymphocytes after alemtuzumab induction together with a correlation with the clinical course is warranted. PMID:26171403

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

    PubMed

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

    2015-01-01

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

  18. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  19. Lymphocyte function in myasthenia gravis.

    PubMed Central

    Kawanami, S; Kanaide, A; Itoyama, Y; Kuroiwa, Y

    1979-01-01

    Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia. PMID:490180

  20. Lymphocyte 'homing' and chronic inflammation.

    PubMed

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

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

  1. Lymphocytic Interstitial Pneumonia.

    PubMed

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

    2016-09-01

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

  2. Depleting depletion: Polymer swelling in poor solvent mixtures

    NASA Astrophysics Data System (ADS)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  3. Leukemia cutis in a patient with chronic lymphocytic leukemia presenting as bilateral helical nodules

    PubMed Central

    Raufi, Ali; Alsharedi, Mohamed; Khelfa, Yousef; Griswold, Doreen C; Lebowicz, Yehuda

    2016-01-01

    Chronic lymphocytic leukemia, the most common adult leukemia worldwide, is considered an indolent but incurable non-Hodgkin lymphoma. Leukemia cutis is an uncommon manifestation of chronic lymphocytic leukemia. We present a case of an adult patient who presented with skin lesion of bilateral ears, which led to the diagnosis of chronic lymphocytic leukemia. We also reviewed the cases of auricular involvement in chronic lymphocytic leukemia patients reported in the literature. Local treatment is indicated in case of leukemia cutis; however, systemic treatment is recommended when there are systemic signs and symptoms. Better awareness of disease evolution and prompt diagnosis of this leukemia cutis of chronic lymphocytic leukemia will improve the effectiveness and outcome of its management. PMID:28228955

  4. Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover.

    PubMed

    Westera, Liset; van Hoeven, Vera; Drylewicz, Julia; Spierenburg, Gerrit; van Velzen, Jeroen F; de Boer, Rob J; Tesselaar, Kiki; Borghans, José A M

    2015-04-01

    In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics.

  5. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  6. [Morphometric analysis of lymphocyte nuclei in chronic lymphocytic leukemia].

    PubMed

    Ostapenko, V A; Kruchinskiĭ, N G; Smirnova, L A; Cherednik, A B; Nesterov, V N; Tepliakov, A I

    1994-01-01

    This work is dedicated to the study of use of quantitative analysis of cell nucleus structure for the analysis of peripheral blood lymphocytes in patients with chronic lymphocytic leukaemia. The structure of lymphocytic nuclei of healthy donors was evaluated by means of staining by toluidine blue purified cell suspensions smears. The preparations were analysed on the television measuring system "omnicon" with measurements of the following parameters: square of the nucleus, euchromatin, heterochromatin, and the ratio of heterochromatin and euchromatin squares. Actuarial analysis and nuclei classification of the previously mentioned parameters showed, that in peripheral blood of patients with chronic lymphocytic leukemia a large amount of atypical lymphocytes is present with reduced nucleus sizes. Atypical cells retain the ratio of structural components of chromatine, characteristic to normal cells, which show their low proliferative activity.

  7. Chronic lymphocytic leukaemia

    PubMed Central

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

    2017-01-01

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

  8. Fully depleted back illuminated CCD

    DOEpatents

    Holland, Stephen Edward

    2001-01-01

    A backside illuminated charge coupled device (CCD) is formed of a relatively thick high resistivity photon sensitive silicon substrate, with frontside electronic circuitry, and an optically transparent backside ohmic contact for applying a backside voltage which is at least sufficient to substantially fully deplete the substrate. A greater bias voltage which overdepletes the substrate may also be applied. One way of applying the bias voltage to the substrate is by physically connecting the voltage source to the ohmic contact. An alternate way of applying the bias voltage to the substrate is to physically connect the voltage source to the frontside of the substrate, at a point outside the depletion region. Thus both frontside and backside contacts can be used for backside biasing to fully deplete the substrate. Also, high resistivity gaps around the CCD channels and electrically floating channel stop regions can be provided in the CCD array around the CCD channels. The CCD array forms an imaging sensor useful in astronomy.

  9. Activated T lymphocytes in uveitis.

    PubMed Central

    Deschênes, J.; Char, D. H.; Kaleta, S.

    1988-01-01

    Two colour flow cytometry techniques were used to assess the activation stages of peripheral and intraocular T lymphocytes in uveitis. Increased numbers of T lymphocytes bearing the interleukin-2 (IL-2) receptors were found in intraocular fluids or peripheral blood or both of 35/51 patients with uveitis. This increased expression of IL-2 receptors on lymphocytes correlated with increased expression of other early T lymphocyte activation markers, HLA-DR and L-35. Both T helper cells (Leu-3A+) and suppressor cells (Leu 2A+) were activated in vivo. A positive correlation was seen between lymphocyte activation and clinical uveitis activity. In idiopathic uveitis activation of Leu-3A lymphocytes (helper/inducer) was significantly increased, and intraocular activation of the Leu-2A lymphocytes (cytotoxic/suppressor) was significantly decreased. These data show that some patients with idiopathic uveitis have a perturbation of T helper cells. Twenty-two of 31 patients with idiopathic uveitis, not associated with systemic disease, had increased peripheral T lymphocyte activation. This finding indicates that in some inflammations believed to be restricted to the eye an abnormal systemic immune activation exists. PMID:2964862

  10. Obinutuzumab in chronic lymphocytic leukemia.

    PubMed

    Dupuis, Jehan

    2015-09-01

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

  11. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.

    PubMed

    Salimi, Ahmad; Motallebi, Abbasali; Ayatollahi, Maryam; Seydi, Enayatollah; Mohseni, Ali Reza; Nazemi, Melika; Pourahmad, Jalal

    2017-04-01

    Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5(+) B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017.

  12. Scaling Aspects of Lymphocyte Trafficking

    PubMed Central

    Perelson, Alan S.; Wiegel, Frederik W.

    2010-01-01

    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 lymph node. Mass-dependent aspects of immune learning and of the immunological self are shown to be not very significant. Our treatment is somewhat heuristic and aims at a combination of immunological data with recent progress in biological scaling. PMID:19084024

  13. Role of Circulating Lymphocytes in Patients with Sepsis

    PubMed Central

    de Pablo, Raul; Monserrat, Jorge; Prieto, Alfredo; Alvarez-Mon, Melchor

    2014-01-01

    Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed. PMID:25302303

  14. Current concepts in diagnosis and treatment of chronic lymphocytic leukemia

    PubMed Central

    Roliński, Jacek

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed type of leukemia in Western Europe and North America, and represents about 30% of all leukemias in adults. Chronic lymphocytic leukemia is a disease of the elderly, who are often in poorer general health and burdened with multiple comorbidities. These factors affect the decision making when choosing an appropriate method of treatment. In recent years there has been significant progress in the treatment of chronic lymphocytic leukemia, first due to the introduction of immunochemotherapy with monoclonal antibodies and latterly small molecules, like tyrosine kinase inhibitors targeting B-cell receptor signaling. This article discusses the current diagnostic principles, the most important prognostic factors and therapeutic options, available in first-line treatment and in refractory/resistant disease, including high-risk CLL, both for patients with good and those with poor performance status. It also presents important novel molecules which have been evaluated in clinical trials. PMID:26793019

  15. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  16. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  17. Lymphocyte abnormalities in ankylosing spondylitis.

    PubMed Central

    Fan, P T; Clements, P J; Yu, D T; Opelz, G; Bluestone, R

    1977-01-01

    Peripheral blood T (SRBC rosette) and B (AgG- and C-receptor) lymphocyte subpopulations and responsiveness to phytohaemagglutinin (PHA) were assayed in 40 patients with ankylosing spondylitis and in 55 normal subjects. There was no significant difference in the lymphocyte concentrations or responsiveness to PHA between the two groups. However, the percentages of T lymphocytes were significantly lower in the patients irrespective of their HLA typing. This was probably due to an increase in the 'null' population since the percentages of both the AgG- and C-receptor cells were normal. PMID:303501

  18. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

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

    SciTech Connect

    Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.; Rosenblatt, L.S.; Reeves, J.D.; Misra, H.

    1981-06-01

    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 and colony formation assay. 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.

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

    SciTech Connect

    Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.; Rosenblatt, L.S.; Reeves, J.D.; Misra, H.

    1981-06-01

    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.

  1. Eimeria tenella infection induces local gamma interferon production and intestinal lymphocyte subpopulation changes.

    PubMed

    Yun, C H; Lillehoj, H S; Choi, K D

    2000-03-01

    The role of intestinal lymphocytes and gamma interferon (IFN-gamma) production in protective immunity to Eimeria tenella infection was evaluated in two inbred strains of chickens (SC and TK) that display different patterns of susceptibility to coccidiosis. Oral inoculation of either strain with E. tenella led to parasite invasion of the intestinal cecum and cecal tonsils. Greater fecal oocyst shedding was seen in TK chickens. Flow cytometric analyses of cecal tonsil lymphocytes demonstrated greater numbers of CD4(+) and T-cell receptor gammadelta-positive (TCR1(+)) cells in SC chickens and elevated numbers of CD8(+) and TCR2(+) cells in TK chickens following primary infection. IFN-gamma mRNA expression was significantly increased in cecal tonsil and intraepithelial lymphocytes at days 6 and 8, respectively, after primary infection in SC compared to TK chickens. While no differences were noted between cecal tonsil lymphocytes of the two strains following secondary infection, TK chickens showed elevated IFN-gamma transcript levels in intestinal intraepithelial lymphocytes at this time. Selective depletion of CD4(+), but not CD8(+), cecal tonsil lymphocytes in SC chickens resulted in a reduced IFN-gamma mRNA expression, indicating that CD4(+) cells are the primary source of this cytokine. Collectively, these results indicate that local lymphocyte responses and production of IFN-gamma are influenced by host genetic factors.

  2. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  3. Ozone depletion, paradigms, and politics

    SciTech Connect

    Iman, R.L.

    1993-10-01

    The destruction of the Earth`s protective ozone layer is a prime environmental concern. Industry has responded to this environmental problem by: implementing conservation techniques to reduce the emission of ozone-depleting chemicals (ODCs); using alternative cleaning solvents that have lower ozone depletion potentials (ODPs); developing new, non-ozone-depleting solvents, such as terpenes; and developing low-residue soldering processes. This paper presents an overview of a joint testing program at Sandia and Motorola to evaluate a low-residue (no-clean) soldering process for printed wiring boards (PWBs). Such processes are in widespread use in commercial applications because they eliminate the cleaning operation. The goal of this testing program was to develop a data base that could be used to support changes in the mil-specs. In addition, a joint task force involving industry and the military has been formed to conduct a follow-up evaluation of low-residue processes that encompass the concerns of the tri-services. The goal of the task force is to gain final approval of the low-residue technology for use in military applications.

  4. Ozone Depletion from Nearby Supernovae

    NASA Technical Reports Server (NTRS)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  5. Chronic Lymphocytic Leukemia

    PubMed Central

    Motta, Marina; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL. PMID:19536902

  6. Quantifying T Lymphocyte Turnover

    PubMed Central

    De Boer, Rob J.; Perelson, Alan S.

    2013-01-01

    Peripheral T cell populations are maintained by production of naive T cells in the thymus, clonal expansion of activated cells, cellular self-renewal (or homeostatic proliferation), and density dependent cell life spans. A variety of experimental techniques have been employed to quantify the relative contributions of these processes. In modern studies lymphocytes are typically labeled with 5-bromo-2′-deoxyuridine (BrdU), deuterium, or the fluorescent dye carboxy-fluorescein diacetate succinimidyl ester (CFSE), their division history has been studied by monitoring telomere shortening and the dilution of T cell receptor excision circles (TRECs) or the dye CFSE, and clonal expansion has been documented by recording changes in the population densities of antigen specific cells. Proper interpretation of such data in terms of the underlying rates of T cell production, division, and death has proven to be notoriously difficult and involves mathematical modeling. We review the various models that have been developed for each of these techniques, discuss which models seem most appropriate for what type of data, reveal open problems that require better models, and pinpoint how the assumptions underlying a mathematical model may influence the interpretation of data. Elaborating various successful cases where modeling has delivered new insights in T cell population dynamics, this review provides quantitative estimates of several processes involved in the maintenance of naive and memory, CD4+ and CD8+ T cell pools in mice and men. PMID:23313150

  7. Dopamine depletion impairs precursor cell proliferation in Parkinson disease.

    PubMed

    Höglinger, Günter U; Rizk, Pamela; Muriel, Marie P; Duyckaerts, Charles; Oertel, Wolfgang H; Caille, Isabelle; Hirsch, Etienne C

    2004-07-01

    Cerebral dopamine depletion is the hallmark of Parkinson disease. Because dopamine modulates ontogenetic neurogenesis, depletion of dopamine might affect neural precursors in the subependymal zone and subgranular zone of the adult brain. Here we provide ultrastructural evidence showing that highly proliferative precursors in the adult subependymal zone express dopamine receptors and receive dopaminergic afferents. Experimental depletion of dopamine in rodents decreases precursor cell proliferation in both the subependymal zone and the subgranular zone. Proliferation is restored completely by a selective agonist of D2-like (D2L) receptors. Experiments with neural precursors from the adult subependymal zone grown as neurosphere cultures confirm that activation of D2L receptors directly increases the proliferation of these precursors. Consistently, the numbers of proliferating cells in the subependymal zone and neural precursor cells in the subgranular zone and olfactory bulb are reduced in postmortem brains of individuals with Parkinson disease. These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation.

  8. Lymphocyte subpopulations in the blood of sheep persistently infected with border disease virus.

    PubMed Central

    Burrells, C; Nettleton, P F; Reid, H W; Miller, H R; Hopkins, J; McConnell, I; Gorrell, M D; Brandon, M R

    1989-01-01

    The surface phenotypes of peripheral blood lymphocytes in groups of lambs and adult sheep persistently infected with Border disease virus (P-I BD) were compared with those of healthy controls. The proportion and number of lymphocytes bearing surface immunoglobulin (sIg+) and expressing class II MHC antigen (B cells) were significantly increased. A significant increase in CD1+ lymphocytes was also evident. Conversely, the proportion of T lymphocytes in P-I BD lambs was reduced. A marked reduction in the proportion of circulating lymphocytes expressing class I MHC antigen was also observed. These findings were not affected by differences in the strain of the virus responsible for the persistent infection. PMID:2787717

  9. Issues in Stratospheric Ozone Depletion.

    NASA Astrophysics Data System (ADS)

    Lloyd, Steven Andrew

    Following the announcement of the discovery of the Antarctic ozone hole in 1985 there have arisen a multitude of questions pertaining to the nature and consequences of polar ozone depletion. This thesis addresses several of these specific questions, using both computer models of chemical kinetics and the Earth's radiation field as well as laboratory kinetic experiments. A coupled chemical kinetic-radiative numerical model was developed to assist in the analysis of in situ field measurements of several radical and neutral species in the polar and mid-latitude lower stratosphere. Modeling was used in the analysis of enhanced polar ClO, mid-latitude diurnal variation of ClO, and simultaneous measurements of OH, HO_2, H_2 O and O_3. Most importantly, such modeling was instrumental in establishing the link between the observed ClO and BrO concentrations in the Antarctic polar vortex and the observed rate of ozone depletion. The principal medical concern of stratospheric ozone depletion is that ozone loss will lead to the enhancement of ground-level UV-B radiation. Global ozone climatology (40^circS to 50^ circN latitude) was incorporated into a radiation field model to calculate the biologically accumulated dosage (BAD) of UV-B radiation, integrated over days, months, and years. The slope of the annual BAD as a function of latitude was found to correspond to epidemiological data for non-melanoma skin cancers for 30^circ -50^circN. Various ozone loss scenarios were investigated. It was found that a small ozone loss in the tropics can provide as much additional biologically effective UV-B as a much larger ozone loss at higher latitudes. Also, for ozone depletions of > 5%, the BAD of UV-B increases exponentially with decreasing ozone levels. An important key player in determining whether polar ozone depletion can propagate into the populated mid-latitudes is chlorine nitrate, ClONO_2 . As yet this molecule is only indirectly accounted for in computer models and field

  10. The effects of glutathione depletion on reproductive success in oysters, Crassostrea virginica.

    PubMed

    Ringwood, A H; Conners, D E

    2000-01-01

    Glutathione (GSH) is a ubiquitous tripeptide that functions as a very important modulator of cellular homeostasis, including detoxification of metals and oxyradicals. Therefore, depletion of GSH may predispose organisms to pollutant stress. Reproductively active oysters (Crassostrea virginica) were exposed to buthionine sulfoximine in the laboratory to deplete gonadal GSH. The effects of metal exposures (Cd and Cu) on fertilization and developmental assays were evaluated using gametes from control and GSH-depleted adults. Fertilization success was not affected by GSH status, i.e. the fertilization rates of gametes derived from GSH-depleted adults were the same or slightly higher. However, GSH depletion did increase the susceptibility of developing embryos to metal toxicity, i.e. adverse effects on embryonic development were observed at lower metal concentrations with gametes derived from GSH-depleted adults. These effects may be related to diminished removal of free radicals or increased availability of metals. Whereas sperm penetration of embryonic membranes and fertilization success may be facilitated by free radicals, the persistence of free radicals during subsequent developmental periods may adversely affect differentiation and normal development. GSH probably also plays an important role in scavenging toxic metals and reducing metal interactions with essential developmental processes. These results suggest that parental depletion of GSH may increase the susceptibility of embryos to metal toxicity.

  11. T-cell chronic lymphocytic leukemia in a double yellow-headed Amazon parrot (Amazona ochrocephala oratrix).

    PubMed

    Osofsky, Anna; Hawkins, Michelle G; Foreman, Oded; Kent, Michael S; Vernau, William; Lowenstine, Linda J

    2011-12-01

    An adult, male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was diagnosed with chronic lymphocytic leukemia based on results of a complete blood cell count and cytologic examination of a bone marrow aspirate. Treatment with oral chlorambucil was attempted, but no response was evident after 40 days. The bird was euthanatized, and the diagnosis of chronic lymphocytic leukemia was confirmed on gross and microscopic examination of tissues. Neoplastic lymphocytes were found in the bone marrow, liver, kidney, testes, and blood vessels. Based on CD3-positive immunocytochemical and immunohistochemical immunophenotyping, the chronic lymphocytic leukemia was determined to be of T-cell origin.

  12. The Case of Ozone Depletion

    NASA Technical Reports Server (NTRS)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  13. Protein depletion and metabolic stress in elderly patients who have a fracture of the hip.

    PubMed

    Patterson, B M; Cornell, C N; Carbone, B; Levine, B; Chapman, D

    1992-02-01

    A prospective study was performed to determine the effect of protein depletion and postoperative nutritional status on the outcome in sixty-three elderly patients who had been admitted to the hospital because of a fracture of the hip. The parameters that were used to determine the degree of protein depletion included levels of albumin, of prealbumin, and of transferrin; total lymphocyte count; and nitrogen-balance studies. The outcomes that were examined were the development of complications, the length of the stay in the hospital, the ability to return to the pre-fracture level of function, and over-all survivorship. The hypothesis was that the acute fracture and the subsequent operation are severe stresses in these elderly, often compromised patients. The results supported the hypothesis. Thirty-seven patients (58 per cent) in the study group were in a protein-depleted state during the period of hospitalization. The patients who were protein-depleted had a higher prevalence of complications, were less likely to return to their pre-fracture environment, and tended to stay in the hospital longer, as compared with the nonprotein-depleted patients. Survivorship analysis showed that protein-depleted patients had a significantly lower probability of survival one year after the fracture of the hip (p = 0.02). Elderly patients who sustain the trauma of a fracture of the hip should be managed appropriately with regard to intake of nutrients in the postoperative period.

  14. Action orientation overcomes the ego depletion effect.

    PubMed

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

  15. Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes.

    PubMed Central

    Mody, C H; Buser, D E; Syme, R M; Woods, D E

    1995-01-01

    Pseudomonas aeruginosa is a gram-negative bacterium that is responsible for devastating acute and chronic infections, which include bronchiectasis in cystic fibrosis, nosocomial pneumonia, and infection of burn wounds. Previous studies have demonstrated that these patients have impaired host responses, including cell-mediated immune responses, which are important in anti-Pseudomonas host defense. The P. aeruginosa exoproduct, exoenzyme S, has a number of characteristics which suggest that it might be important in cell-mediated immunity. To determine whether exoenzyme S activates lymphocytes to proliferate, peripheral blood mononuclear cells (PBMC) from normal volunteers were stimulated with purified exoenzyme S, and the lymphocyte response was assessed by measuring [3H]thymidine uptake and by counting the number of cells after various times in culture. Ninety-five percent of healthy adult donors had a lymphocyte response to exoenzyme S. The optimal lymphocyte response occurred on day 7, with 4 x 10(5) PBMC per microtiter well when cells were stimulated with 10 micrograms exoenzyme S per ml. [3H]thymidine uptake correlated with an increase in the number of mononuclear cells, indicating that proliferation occurred. In unseparated PBMC, T cells, and to a lesser extent B cells, proliferated. Purified T cells proliferated, while purified B cells proliferated only after the addition of irradiated T cells. Thus, T lymphocytes are necessary and sufficient for the proliferative response to exoenzyme S. We speculate that exoenzyme S from P. aeruginosa is important in T-lymphocyte-mediated host defense to P. aeruginosa. In strategies to enhance impaired cell-mediated immunity, exoenzyme S should be considered as a potential stimulant. PMID:7537248

  16. Biomedical consequences of ozone depletion

    NASA Astrophysics Data System (ADS)

    Coohill, Thomas P.

    1994-07-01

    It is widely agreed that a portion of the earth's protective stratospheric ozone layer is being depleted. The major effect of this ozone loss will be an increase in the amount of ultraviolet radiation (UV reaching the biosphere. This increase will be completely contained within the UVB (290nm - 320nm). It is imperative that assessments be made of the effects of this additional UVB on living organisms. This requires a detailed knowledge of the UVB photobiology of these life forms. One analytical technique to aid in the approximations is the construction of UV action spectra for such important biological end-points as human skin cancer, cataracts, immune suppression; plant photosynthesis and crop yields; and aquatic organism responses to UVB, especially the phytoplankton. Combining these action spectra with the known solar spectrum (and estimates for various ozone depletion scenarios) can give rise to a series of effectiveness spectra for these parameters. This manuscript gives a first approximation, rough estimate, for the effectiveness spectra for some of these bioresponses, and a series of crude temporary values for how a 10% ozone loss would affect the above end-points. These are not intended to masquerade as final answers, but rather, to serve as beginning attempts for a process which should be continually refined. It is hoped that these estimates will be of some limited use to agencies, such as government and industry, that have to plan now for changes in human activities that might alter future atmospheric chemistry in a beneficial manner.

  17. Tumor infiltrating lymphocytes in ovarian cancer.

    PubMed

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

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

  18. B-1a Lymphocytes Attenuate Insulin Resistance

    PubMed Central

    Shen, Lei; Chng, MH; Alonso, Michael N.; Yuan, Robert

    2015-01-01

    Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell–derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell–deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell–activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell–depleting, B-1a cell–sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance. PMID:25249575

  19. Splenic lymphoma with villous lymphocytes.

    PubMed

    Gupta, Ritu; Naseem, Shano; Sukumaran, Shawgi; Kashyap, Rajesh; Kaur, Sukhpreet; Paul, Lily

    2008-01-01

    Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.

  20. Fatty acids and lymphocyte functions.

    PubMed

    Calder, P C; Yaqoob, P; Thies, F; Wallace, F A; Miles, E A

    2002-01-01

    The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.

  1. Glucose, glycolysis and lymphocyte responses.

    PubMed

    Donnelly, Raymond P; Finlay, David K

    2015-12-01

    Activated lymphocytes engage in robust growth and rapid proliferation. To achieve this, they tend to adopt a form of glucose metabolism termed aerobic glycolysis. This type of metabolism allows for the use of large amounts of glucose to generate energy, but also to support biosynthetic processes. This review article will discuss how aerobic glycolysis supports the biosynthetic demands of activated T cells, B cells and Natural Killer cells, and the emerging concept that glycolysis is integrally linked to the differentiation and function of these lymphocyte populations.

  2. Depleted Argon from Underground Sources

    SciTech Connect

    Back, H. O.; Galbiati, C.; Goretti, A.; Loer, B.; Montanari, D.; Mosteiro, P.; Alexander, T.; Alton, A.; Rogers, H.; Kendziora, C.; Pordes, S.

    2011-04-27

    Argon is a strong scintillator and an ideal target for Dark Matter detection; however {sup 39}Ar contamination in atmospheric argon from cosmic ray interactions limits the size of liquid argon dark matter detectors due to pile-up. Argon from deep underground is depleted in {sup 39}Ar due to the cosmic ray shielding of the earth. In Cortez, Colorado, a CO{sub 2} well has been discovered to contain approximately 600 ppm of argon as a contamination in the CO{sub 2}. We first concentrate the argon locally to 3% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation, and then the N{sub 2} and He will be removed by continuous distillation to purify the argon. We have collected 26 kg of argon from the CO{sub 2} facility and a cryogenic distillation column is under construction at Fermilab to further purify the argon.

  3. Characterization of lymphocyte transformation induced by zinc ions.

    PubMed

    Berger, N A; Skinner, A M

    1974-04-01

    Lymphocyte cultures from all normal human adults are stimulated by zinc ions to increase DNA and RNA synthesis and undergo blast transformation. Optimal stimulation occurs at 0.1 mM Zn(++). Examination of the effects of other divalent cations reveals that 0.01 mM Hg(++) also stimulates lymphocyte DNA synthesis. Ca(++) and Mg(++) do not affect DNA synthesis in this culture system, while Mn(++), Co(++), Cd(++), Cu(++), and Ni(++) at concentrations of 10(-7)-10(-3) M are inhibitory. DNA and RNA synthesis and blast transformation begin to increase after cultures are incubated for 2-3 days with Zn(++) and these processes reach a maximum rate after 6 days. The increase in Zn(++)-stimulated lymphocyte DNA synthesis is prevented by rendering cells incapable of DNA-dependent RNA synthesis with actinomycin D or by blocking protein synthesis with cycloheximide or puromycin. Zn(++)-stimulated DNA synthesis is also partially inhibited by 5'-AMP and chloramphenicol. Zn(++) must be present for the entire 6-day culture period to produce maximum stimulation of DNA synthesis. In contrast to its ability to independently stimulate DNA synthesis, 0.1 mM Zn(++) inhibits DNA synthesis in phytohemagglutinin-stimulated lymphocytes and L1210 lymphoblasts.

  4. Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD)

    MedlinePlus

    ... for Hodgkin Disease Treating Classic Hodgkin Disease, by Stage Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD) Treating Hodgkin Disease in Children Hodgkin Disease in Pregnancy Hodgkin Disease Treating Hodgkin Disease Treating Nodular Lymphocyte ...

  5. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, Suresh C.; Fawwaz, Rashid A.; Richards, Powell

    1985-01-01

    Lymphocytes labelled with .beta.-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

  6. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, S.C.; Fawwaz, R.A.; Richards, P.

    1983-05-03

    Lymphocytes labelled with ..beta..-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

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

    MedlinePlus

    ... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  8. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  9. What Should You Ask Your Doctor about Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Should You Ask Your Doctor About Chronic Lymphocytic Leukemia? As you cope with cancer and cancer treatment, ... About Chronic Lymphocytic Leukemia? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  10. Do We Know What Causes Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Prevention Do We Know What Causes Chronic Lymphocytic Leukemia? The exact cause of most cases of chronic ... Lymphocytic Leukemia Be Prevented? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  11. What Are the Risk Factors for Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... What Are the Risk Factors for Chronic Lymphocytic Leukemia? A risk factor is something that affects a ... Lymphocytic Leukemia Be Prevented? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  12. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

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

  13. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    PubMed Central

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

    2017-01-01

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

  14. Lymphocyte receptors for pertussis toxin

    SciTech Connect

    Clark, C.G.; Armstrong, G.D. )

    1990-12-01

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

  15. High-voltage-compatible, fully depleted CCDs

    SciTech Connect

    Holland, Stephen E.; Bebek, Chris J.; Dawson, Kyle S.; Emes, JohnE.; Fabricius, Max H.; Fairfield, Jessaym A.; Groom, Don E.; Karcher, A.; Kolbe, William F.; Palaio, Nick P.; Roe, Natalie A.; Wang, Guobin

    2006-05-15

    We describe charge-coupled device (CCD) developmentactivities at the Lawrence Berkeley National Laboratory (LBNL).Back-illuminated CCDs fabricated on 200-300 mu m thick, fully depleted,high-resistivity silicon substrates are produced in partnership with acommercial CCD foundry.The CCDs are fully depleted by the application ofa substrate bias voltage. Spatial resolution considerations requireoperation of thick, fully depleted CCDs at high substrate bias voltages.We have developed CCDs that are compatible with substrate bias voltagesof at least 200V. This improves spatial resolution for a given thickness,and allows for full depletion of thicker CCDs than previously considered.We have demonstrated full depletion of 650-675 mu m thick CCDs, withpotential applications in direct x-ray detection. In this work we discussthe issues related to high-voltage operation of fully depleted CCDs, aswell as experimental results on high-voltage-compatible CCDs.

  16. Mixed lymphocyte culture stimulatory and responding capacity of lymphocytes from patients with lymphoproliferative diseases.

    PubMed Central

    Rühl, H; Vogt, W; Bochert, G; Schmidt, S; Moelle, R; Schaoua, H

    1975-01-01

    Lymphocyte reactivity in vitro was studied in patients with Hodgkin's disease, chronic lymphocytic leukaemia and lymphosarcoma. The responding capacity to phytohaemagglutinin (PHA) was markedly depressed and delayed in all three groups of patients compared with the PHA response observed in lymphocyte cultures from normal individuals. In one-way mixed lymphocyte culture experiments a significant decrease in responding capacity of the patients' lymphocytes to lymphocytes from normal donors could be demonstrated. In contrast, the stimulatory capacity of the patients' lymphocytes was found to be intact, or only slightly reduced. PMID:128426

  17. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease

    PubMed Central

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-01-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2–6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L+ T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4+CD25hiFoxP3+ Treg, which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT. PMID:21498586

  18. Ego depletion increases risk-taking.

    PubMed

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  19. CO depletion in the Gould Belt clouds

    NASA Astrophysics Data System (ADS)

    Christie, H.; Viti, S.; Yates, J.; Hatchell, J.; Fuller, G. A.; Duarte-Cabral, A.; Sadavoy, S.; Buckle, J. V.; Graves, S.; Roberts, J.; Nutter, D.; Davis, C.; White, G. J.; Hogerheijde, M.; Ward-Thompson, D.; Butner, H.; Richer, J.; Di Francesco, J.

    2012-05-01

    We present a statistical comparison of CO depletion in a set of local molecular clouds within the Gould Belt using Sub-millimetre Common User Bolometer Array (SCUBA) and Heterodyne Array Receiver Programme (HARP) data. This is the most wide-ranging study of depletion thus far within the Gould Belt. We estimate CO column densities assuming local thermodynamic equilibrium and, for a selection of sources, using the radiative transfer code RADEX in order to compare the two column density estimation methods. High levels of depletion are seen in the centres of several dust cores in all the clouds. We find that in the gas surrounding protostars, levels of depletion are somewhat lower than for starless cores with the exception of a few highly depleted protostellar cores in Serpens and NGC 2024. There is a tentative correlation between core mass and core depletion, particularly in Taurus and Serpens. Taurus has, on average, the highest levels of depletion. Ophiuchus has low average levels of depletion which could perhaps be related to the anomalous dust grain size distribution observed in this cloud. High levels of depletion are often seen around the edges of regions of optical emission (Orion) or in more evolved or less dynamic regions such as the bowl of L1495 in Taurus and the north-western region of Serpens.

  20. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

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

    ClinicalTrials.gov

    2016-07-18

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

  2. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  3. Beneficial Uses of Depleted Uranium

    SciTech Connect

    Brown, C.; Croff, A.G.; Haire, M. J.

    1997-08-01

    Naturally occurring uranium contains 0.71 wt% {sup 235}U. In order for the uranium to be useful in most fission reactors, it must be enriched the concentration of the fissile isotope {sup 235}U must be increased. Depleted uranium (DU) is a co-product of the processing of natural uranium to produce enriched uranium, and DU has a {sup 235}U concentration of less than 0.71 wt%. In the United States, essentially all of the DU inventory is in the chemical form of uranium hexafluoride (UF{sub 6}) and is stored in large cylinders above ground. If this co-product material were to be declared surplus, converted to a stable oxide form, and disposed, the costs are estimated to be several billion dollars. Only small amounts of DU have at this time been beneficially reused. The U.S. Department of Energy (DOE) has begun the Beneficial Uses of DU Project to identify large-scale uses of DU and encourage its reuse for the primary purpose of potentially reducing the cost and expediting the disposition of the DU inventory. This paper discusses the inventory of DU and its rate of increase; DU disposition options; beneficial use options; a preliminary cost analysis; and major technical, institutional, and regulatory issues to be resolved.

  4. Depleted argon from underground sources

    SciTech Connect

    Back, H.O.; Alton, A.; Calaprice, F.; Galbiati, C.; Goretti, A.; Kendziora, C.; Loer, B.; Montanari, D.; Mosteiro, P.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  5. Depleted uranium--the growing concern.

    PubMed

    Abu-Qare, Aqel W; Abou-Donia, Mohamed B

    2002-01-01

    Recently, several studies have reported on the health and environmental consequences of the use of depleted uranium. Depleted uranium is a heavy metal that is also radioactive. It is commonly used in missiles as a counterweight because of its very high density (1.6 times more than lead). Immediate health risks associated with exposure to depleted uranium include kidney and respiratory problems, with conditions such as kidney stones, chronic cough and severe dermatitis. Long-term risks include lung and bone cancer. Several published reports implicated exposure to depleted uranium in kidney damage, mutagenicity, cancer, inhibition of bone, neurological deficits, significant decrease in the pregnancy rate in mice and adverse effects on the reproductive and central nervous systems. Acute poisoning with depleted uranium elicited renal failure that could lead to death. The environmental consequences of its residue will be felt for thousands of years. It is inhaled and passed through the skin and eyes, transferred through the placenta into the fetus, distributed into tissues and eliminated in urine. The use of depleted uranium during the Gulf and Kosovo Wars and the crash of a Boeing airplane carrying depleted uranium in Amsterdam in 1992 were implicated in a health concern related to exposure to depleted uranium.

  6. Lymphocytic hypophysitis in a man.

    PubMed

    Guay, A T; Agnello, V; Tronic, B C; Gresham, D G; Freidberg, S R

    1987-03-01

    Fewer than 20 patients with lymphocytic adenohypophysitis have been reported, all of them women, and it usually occurs during pregnancy or the postpartum period. We report the recognition of lymphocytic adenohypophysitis in a man. The patient presented with anterior hypopituitarism and an intrasellar mass on computed tomography. Antipituitary antibodies, found in only one of the previous patients, were not present in this man, although low titer antinuclear antibodies were found. The implications of this latter finding are unclear. The patient's histocompatibility antigen (HLA) types were A2, B8, Bw58, DR1, and DR5. The degree of pituitary failure seemed out of proportion to the size of the mass seen on computed tomographic scan.

  7. High homocysteine induces betaine depletion

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

    2015-01-01

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

  8. Gulf war depleted uranium risks.

    PubMed

    Marshall, Albert C

    2008-01-01

    US and British forces used depleted uranium (DU) in armor-piercing rounds to disable enemy tanks during the Gulf and Balkan Wars. Uranium particulate is generated by DU shell impact and particulate entrained in air may be inhaled or ingested by troops and nearby civilian populations. As uranium is slightly radioactive and chemically toxic, a number of critics have asserted that DU exposure has resulted in a variety of adverse health effects for exposed veterans and nearby civilian populations. The study described in this paper used mathematical modeling to estimate health risks from exposure to DU during the 1991 Gulf War for both US troops and nearby Iraqi civilians. The analysis found that the risks of DU-induced leukemia or birth defects are far too small to result in an observable increase in these health effects among exposed veterans or Iraqi civilians. The analysis indicated that only a few ( approximately 5) US veterans in vehicles accidentally targeted by US tanks received significant exposure levels, resulting in about a 1.4% lifetime risk of DU radiation-induced fatal cancer (compared with about a 24% risk of a fatal cancer from all other causes). These veterans may have also experienced temporary kidney damage. Iraqi children playing for 500 h in DU-destroyed vehicles are predicted to incur a cancer risk of about 0.4%. In vitro and animal tests suggest the possibility of chemically induced health effects from DU internalization, such as immune system impairment. Further study is needed to determine the applicability of these findings for Gulf War exposure to DU. Veterans and civilians who did not occupy DU-contaminated vehicles are unlikely to have internalized quantities of DU significantly in excess of normal internalization of natural uranium from the environment.

  9. High homocysteine induces betaine depletion.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  10. Specification for the VERA Depletion Benchmark Suite

    SciTech Connect

    Kim, Kang Seog

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  11. Depletion of NK cells in a murine polytrauma model is associated with improved outcome and a modulation of the inflammatory response.

    PubMed

    Barkhausen, Tanja; Frerker, Christian; Pütz, Claudia; Pape, Hans-Christoph; Krettek, Christian; van Griensven, Martijn

    2008-10-01

    Sepsis and associated diseases such as systemic inflammatory response syndrome and multiple organ dysfunction syndrome represent common posttraumatic complications on intensive care units induced by a variety of body defense mechanisms. Natural killer (NK) cells are part of the innate immune system. They are thought to play an important role in the development of such syndromes by interplay with other immune cell types and subsequent activation of the inflammatory cascade. To test this hypothesis, NK cells were depleted by administration of antimouse asialo-GM1 antibody in a murine polytrauma model consisting of femur fracture, hemorrhagic shock, and subsequent sepsis. Mortality and immune parameters such as cytokine expression in lung and liver, lymphocyte phenotyping, lymphocyte apoptosis, and organ pathology were determined 96 h after sepsis induction. Survival values showed 50% in the control sepsis group and 100% after NK cell depletion. Thus, NK cell depletion resulted in 50% mortality reduction. Furthermore, we found reductions in the inflammatory response, represented by IL-6 expression in liver, and a decrease in infiltrating neutrophils in the liver and lung. In addition, lymphocyte apoptosis in spleen was decreased by depletion of NK cells. Taken together, these data demonstrate that NK cells contribute to the pathogenetic pathways in a murine polytrauma model. One main mechanism of action seems to be the induction of systemic inflammatory events. Thus, depletion of NK cells results in attenuated inflammation and an overall improvement in outcome. Therefore, NK cells can be considered as important targets for therapeutic strategies.

  12. Lymphocytic enteritis in a filly.

    PubMed

    Clark, E S; Morris, D D; Allen, D; Tyler, D E

    1988-11-15

    A yearling Hanoverian filly had intermittent colic for 6 weeks, chylous peritoneal effusion, and a firm mass palpable per rectum. Exploratory laparotomy revealed mesenteric lymphadenopathy, adhesion of the mesenteric root to the duodenum and jejunum, distention of the mesenteric veins and lymphatic vessels, and increased jejunal venous pressure. Lesions in the duodenum, jejunum, and colon included infiltration of lymphocytes and plasma cells in the lamina propria.

  13. THE USE OF SPECIFIC "LYMPHOCYTE" ANTISERA TO INHIBIT HYPERSENSITIVE REACTIONS OF THE "DELAYED" TYPE

    PubMed Central

    Waksman, Byron H.; Arbouys, Simone; Arnason, Barry G.

    1961-01-01

    Rabbit antisera against normal guinea pig lymph node, when injected into guinea pigs, produced transient depression of the level of blood lymphocytes. It had no effect on other circulating cellular elements. Repeated injection over several days produced lymphopenia, which became progressively less marked with continued treatment, and clear-cut depletion of small lymphocytes in lymph nodes, whether draining an inoculation site or remote. In guinea pigs treated with lymphocyte antiserum, there was marked suppression of the tuberculin and contact allergic reactions and the "delayed" skin reaction to purified diphtheria toxoid, and a relative suppression of allergic encephalomyelitis and the rejection of first set skin homografts. There was a slight effect on second set graft rejection and no effect on PCA or the reversed passive Arthus reaction. Non-specific reactions to intradermal turpentine or to concentrated dinitrochlorobenzene placed on the skin were moderately reduced. The suppression of these reactions (except allergic encephalomyelitis) was closely correlated with the degree of lymphopenia. Lymphocyte antiserum absorbed with normal blood white cells lost both its lymphopenic effect and its ability to suppress the tuberculin reaction. It is tentatively concluded that a circulating mononuclear cell, probably the small lymphocyte, is the primary reactant in the various types of delayed hypersensitive reactions. PMID:14004486

  14. Evolution of the peripheral blood lymphocyte populations in multiparous rabbit does with two reproductive management rhythms.

    PubMed

    Guerrero, Irene; Ferrian, Selena; Blas, Enrique; Pascual, Juan J; Cano, José L; Corpa, Juan M

    2011-03-15

    The emergence of epizootic rabbit enteropathy is leading to changes in weaning protocols in commercial rabbitries. Traditional weaning protocols are being replaced with late weaning, beyond 35 days postpartum (dpp). The main objectives of this study were to compare the peripheral blood lymphocyte populations of multiparous rabbit does under two reproductive rhythms (insemination at 11 dpp and weaning at 28 dpp, insemination at 25 dpp and weaning at 42 dpp), and to assess the influence on those of kits. Samples of peripheral blood were taken in 22 adult females and 44 of their kits at different critical times, and several lymphocytic populations were evaluated by flow cytometry. Additionally, the perirenal fat thickness of does was also measured at partum and weaning to observe if body condition correlates with lymphocyte populations. During whole lactation, counts of total, CD5(+), CD4(+) and CD8(+) lymphocytes of females were generally lower with weaning at 42 dpp compared to 28 dpp. Moreover, counts of total, B and CD5(+) lymphocytes in rabbit does weaned at 42 dpp correlated to their body condition (+0.60 to 0.82; P<0.05), contrary to that observed in rabbit does weaned at 28 dpp. Some correlations between lymphocyte counts in both groups of does and weaning rabbits were observed. At weaning, those young rabbits weaned at 42 dpp had a significantly lower number of CD4(+) lymphocytes than those weaned at 28 dpp (P<0.01). In conclusion, the 42 ddp rabbit does presented a lower number of total lymphocytes and lymphocytic subpopulations during lactation and at weaning, as well as lesser capacity of adjustment during the gestation-lactation cycle.

  15. B Lymphocytes Differentially Influence Acute and Chronic Allograft Rejection in Mice1

    PubMed Central

    DiLillo, David J.; Griffiths, Robert; Seshan, Surya V.; Magro, Cynthia M.; Ruiz, Phillip; Coffman, Thomas M.; Tedder, Thomas F.

    2013-01-01

    The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD19 mAbs. Both CD20 and CD19 mAbs effectively depleted mature B cells, while CD19 mAb treatment depleted plasmablasts and some plasma cells. B cell depletion did not affect acute cardiac allograft rejection, although CD19 mAb treatment prevented allograft-specific IgG production. Strikingly, CD19 mAb treatment significantly reduced renal allograft rejection and abrogated allograft-specific IgG development, while CD20 mAb treatment did not. By contrast, B cell depletion exacerbated skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells, demonstrating that B cells can also negatively regulate allograft rejection. Thereby, B cells can either positively or negatively regulate allograft rejection depending on the nature of the allograft and the intensity of the rejection response. Moreover, CD19 mAb may represent a new approach for depleting both B cells and plasma cells to concomitantly impair T cell activation, inhibit the generation of new allograft-specific Abs, or reduce preexisting allograft-specific Ab levels in transplant patients. PMID:21248259

  16. Reference ranges of hematology and lymphocyte subsets in healthy Korean native cattle (Hanwoo) and Holstein dairy cattle.

    PubMed

    Kim, Yun-Mi; Lee, Jin-A; Jung, Bock-Gie; Kim, Tae-Hoon; Lee, Bong-Joo; Suh, Guk-Hyun

    2016-06-01

    There are no accurate reference ranges for hematology parameters and lymphocyte subsets in Korean native beef cattle (Hanwoo). This study was performed to establish reliable reference ranges of hematology and lymphocyte subsets using a large number of Hanwoo cattle (n = 350) and to compare differences between Hanwoo and Holstein dairy cattle (n = 334). Additionally, age-related changes in lymphocyte subsets were studied. Bovine leukocyte subpopulation analysis was performed using mono or dual color flow cytometry. The leukocyte subpopulations investigated in healthy cattle included: CD2(+) cells, sIgM(+) cells, MHC class II(+) cells, CD3(+) CD4(+) cells, CD3(+) CD8(+) cells, and WC1(+) cells. Although Hanwoo and Holstein cattle are the same species, results showed several differences in hematology and lymphocyte subsets between Hanwoo and Holstein cattle. This study is the first report to establish reference ranges of hematology and lymphocyte subsets in adult Hanwoo cattle.

  17. Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  18. Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T-lymphocytes.

    PubMed

    Telford, G; Wheeler, D J; Appleby, P; Bowen, J G; Pritchard, D I

    1998-12-01

    Experiments were performed to investigate the immunological site of action of an immunomodulatory factor (IMF), isolated from the gastrointestinal nematode Heligmosomoides polygyrus. IMF inhibited antibody production in murine and human 'T-helper (Th-2) driven' immunoassays. The effects were mediated via T lymphocytes as T cell-depleted cultures failed to respond to IMF, a result confirmed by prepulsing discrete cell subsets with the immunomodulant. Although the molecular nature and mode of action of IMF has yet to be determined, it would appear to be a relatively small non-proteinaceous molecule. From this data, we suggest that H. polygyrus secretes a systemically-active IMF from the intestinal lumen, to down-regulate Th-2 cell development in order to promote its survival in a potentially immunologically hostile environment.

  19. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle.

    PubMed

    McCarthy, John J; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B; Srikuea, Ratchakrit; Lawson, Benjamin A; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S; Esser, Karyn A; Dupont-Versteegden, Esther E; Peterson, Charlotte A

    2011-09-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca(2+) sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.

  20. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation.

    PubMed

    Shah, Nirali N; Baird, Kristin; Delbrook, Cynthia P; Fleisher, Thomas A; Kohler, Mark E; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K; Kleiner, David E; Merchant, Melinda S; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F; Wayne, Alan S; Zhang, Hua; Fry, Terry J; Mackall, Crystal L

    2015-01-29

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 × 10(4) T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+)IL-15Rα(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104.

  1. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell–depleted stem cell transplantation

    PubMed Central

    Shah, Nirali N.; Baird, Kristin; Delbrook, Cynthia P.; Fleisher, Thomas A.; Kohler, Mark E.; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K.; Kleiner, David E.; Merchant, Melinda S.; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F.; Wayne, Alan S.; Zhang, Hua; Fry, Terry J.

    2015-01-01

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL–activated NK cells (aNK-DLI) following HLA-matched, T-cell–depleted (1-2 × 104 T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3+-depleted, CD56+-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL+IL-15Rα+ artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104. PMID:25452614

  2. In vitro incubation of bone marrow and peripheral stem cells with vincristine and methylprednisolone: functional T-cell depletion for haploidentical and autologous transplants.

    PubMed

    Fragonas, E; Perticarari, S; Presani, G; Rabusin, M; Andolina, M; Mangiarotti, M A

    2000-11-01

    A mismatched bone marrow transplantation is feasible only if the donor's marrow lymphocytes are eliminated from the graft. This can be achieved by several methods, but all have the disadvantage of inducing a long-lasting immune deficiency while the risk of graft rejection and leukemic relapse increase. We use a sort of functional T-cell depletion by treating the cells with vincristine and methylprednisolone. This method is surely the cheapest and has allowed us to perform 60 transplants with a tolerable risk of GVHD. The treatment of the donor's lymphocytes has already been demonstrated to be able to block the mixed lymphocyte culture reaction in vitro. In this experiment Th1 and Th2 activities were almost completely blocked without reduction of lymphocyte viability and apoptosis induction.

  3. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  4. Fully Depleted Charge-Coupled Devices

    SciTech Connect

    Holland, Stephen E.

    2006-05-15

    We have developed fully depleted, back-illuminated CCDs thatbuild upon earlier research and development efforts directed towardstechnology development of silicon-strip detectors used inhigh-energy-physics experiments. The CCDs are fabricated on the same typeof high-resistivity, float-zone-refined silicon that is used for stripdetectors. The use of high-resistivity substrates allows for thickdepletion regions, on the order of 200-300 um, with corresponding highdetection efficiency for near-infrared andsoft x-ray photons. We comparethe fully depleted CCD to thep-i-n diode upon which it is based, anddescribe the use of fully depleted CCDs in astronomical and x-ray imagingapplications.

  5. Possible ozone depletions following nuclear explosions

    NASA Technical Reports Server (NTRS)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  6. Developing Connections among B Lymphocytes and Deregulated Pathways in Autoimmunity

    PubMed Central

    Zouali, Moncef; Tsay, Gregory

    2016-01-01

    Immunologists have long investigated B lymphocytes as solely antibody-producing cells. With further studies, it became clear that B cells can exert a variety of functions within the immune system and beyond. As a result, B cells are considered promising targets for immunotherapy in a variety of disorders. Recently, experts in B cell biology and autoimmunity convened to discuss important stepping stones to decipher the complexity of B lymphocyte–mediated pathways in autoimmune diseases. Twenty-five years ago, the first report describing the clinical efficacy of depleting B lymphocytes in autoimmune diseases was published (1). This also marked organization of the first International Conference on B Cells and Autoimmunity, held in 2001 in Bergen, Norway. Since then, the credentials of B cells as essential players in autoimmune disease have been well established. For its sixth edition, this conference series settled along the shores of Sun Moon Lake in the heart of Taiwan on August 16–18, 2016, to view and discuss recent advances in different facets of B cell biology and put them in the perspective of understanding autoimmunity and designing effective immunointervention strategies. Following the tradition established in 2001, the conference was a forum where basic immunologists and their clinically trained colleagues met to discuss hot topics of autoimmunity research. Speakers from four continents discussed some of their new data and insights and brought considerable excitement to the conference in the refreshingly beautiful and elegant landscape of Sun Moon Lake and its indescribable charm. PMID:27730250

  7. Obinutuzumab for the treatment of chronic lymphocytic leukemia.

    PubMed

    Rogers, K A; Jones, J A

    2014-06-01

    Obinutuzumab is a novel therapeutic anti-CD20 monoclonal antibody recently approved by the United States Food and Drug Administration (FDA) for use in combination with chlorambucil as first-line treatment of chronic lymphocytic leukemia (CLL). It is distinguished from other anti-B-lymphocyte antigen CD20 (anti-CD20) therapeutic antibodies in current clinical use by its type II properties and glycoengineered Fc region. In vitro these unique properties translate into higher rates of antibody-dependent cytotoxicity and direct cell death compared to rituximab, and obinutuzumab demonstrates improved efficacy in human lymphoma xenograft models and whole blood lymphocyte depletion assays. FDA approval was based upon results from a randomized phase III trial comparing treatment with single-agent chlorambucil to the combination of chlorambucil and either rituximab or obinutuzu-mab. The obinutuzumab arm resulted in higher rates of complete remission and significant improvements in progression-free survival versus either comparator regimen. The majority of patients in the obinutuzumab and chlorambucil arm finished all six planned treatment cycles, and therapy was well tolerated. Toxicities of obinutuzumab are similar to those of other anti-CD20 antibodies, although infusion-related reactions and neutropenia appear to be more common. This trial establishes chemoimmunotherapy with obinutuzumab and chlorambucil as an attractive treatment option for CLL patients, particularly those with comorbid medical illnesses or advanced age. Obinutuzumab remains under study in combination with both chemotherapy and novel agents for CLL and non-Hodgkin's lymphoma, where it is expected to find additional clinical applications.

  8. Cross-reactivity of sperm and T lymphocyte antigens.

    PubMed

    Mathur, S; Goust, J M; Williamson, H O; Fudenberg, H H

    1981-01-01

    Evidence is presented for cross-reactivity between antigens on human sperm and T lymphocytes. In 25 infertile couples in which both the males and females had significant antisperm immunity, antibody (Ab) titers to thymocytes (mean +/- S.E.M. 159 +/- 4 and 72 +/- 14, respectively, in males and females), T cell lines CCRF-CEM (69 +/- 5 and 48 +/- 8) and HSB-2 (56 +/- 15) and 41 +/- 8), suppressor-enriched (TG) cells (26 +/- 6 and 66 +/- 28) and helper-enriched (TG-) cells (26 +/- 4 and 46 +/- 14) were significantly elevated, as compared with Ab titers in 45 normal males and 45 normal females without antisperm immunity. Antibody titers to adult B cells, B cell line RAJI, and granulocytes were similar in the two groups. Antisperm Ab titers in sera, sperm extracts, and seminal plasma of the infertile subjects were significantly reduced after absorption with sperm, thymocytes, or T cell line CCRF-CEM but not with the B cell line RAJI. Antithymocyte Ab titers in the sera were significantly reduced (p less than 0.001) after absorption with thymocytes, CCRF-CEM, or sperm, but not RAJI. Lymphocytes from the infertile patients, when stimulated with pokeweed mitogen in vitro, produced antisperm and anti-T-lymphocyte antibodies at significantly higher titers than normal controls.

  9. Lymphocytic esophagitis: Still an enigma a decade later

    PubMed Central

    Rouphael, Carol; Gordon, Ilyssa O; Thota, Prashanthi N

    2017-01-01

    Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity. PMID:28246468

  10. Lymphocytic esophagitis: Still an enigma a decade later.

    PubMed

    Rouphael, Carol; Gordon, Ilyssa O; Thota, Prashanthi N

    2017-02-14

    Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity.

  11. Human mixed lymphocyte culture using separated lymphocyte populations.

    PubMed Central

    Potter, M R; Moore, M

    1977-01-01

    The ability of human blood lymphocyte populations enriched with T or B cells to act as responder and stimulator populations in the one-way mixed lymphocyte reaction (MLR) was investigated. T- and B-cell-enriched populations were obtained by separation of rosette-forming and non rosette-forming cells and T-cell-enriched populations were also obtained by nylon-fibre column filtration. Using cells prepared by rosette sedimentation, control unseparated and T-cell-enriched populations responded well when stimulated by mitomycin C-treated unseparated cells from a second individual; and stimulation by T- and B-enriched populations generally produced some response, although the magnitude was variable. B-cell-enriched populations gave virtually no response regardless of the composition of the stimulating populations. Nylon-column-enriched T-cell populations responded to stimulation by control unseparated cells but not to T cells purified by the same procedure. T-cell enriched populations prepared by the two methods thus had different activities in the MLR despite containing similar numbers of T cells suggesting that other factors, such as the presence of small numbers of accessory cells, are important in determining the magnitude of the MLR. PMID:139361

  12. Adipose tissue lymphocytes: types and roles.

    PubMed

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  13. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2017-01-06

    B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  14. Exhaustible Resource Depletion: A Modified Graphical Approach.

    ERIC Educational Resources Information Center

    Tisato, Peter

    1995-01-01

    Presents a graphical analysis of the exhaustible resource depletion problem. Applies Hotelling's "r percent rule" as a new approach that operates in an "N"-period context. Includes two figures illustrating the approach. (CFR)

  15. Polar stratospheric clouds and ozone depletion

    NASA Technical Reports Server (NTRS)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  16. A definition of depletion of fish stocks

    USGS Publications Warehouse

    Van Oosten, John

    1949-01-01

    Attention was focused on the need of a common and better understanding of the term depletion as applied to the fisheries in order to eliminate if possible the existing inexactness of thought on the subject. Depletion has been confused at various times with at least ten different ideas associated with it but which, as has has heen pointed out, are not synonymous at all. In defining depletion we must recognize that the term represents a condition and must not he confounded with the cause (overfishing) that leads to this condition or with the symptoms that identify it. Depletion was defined as a reduction, through overfishing, in the level of abundance of the exploitable segment of a stock that prevents the realization of the maximum productive capacity.

  17. The cloning of T lymphocytes.

    PubMed

    Schwartz, R H

    1982-02-01

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

  18. Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy

    ClinicalTrials.gov

    2014-06-18

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Childhood Lymphocyte Depletion Hodgkin Lymphoma; Childhood Lymphocyte Predominant Hodgkin Lymphoma; Childhood Mixed Cellularity Hodgkin Lymphoma; Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma; Childhood Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Childhood Hodgkin Lymphoma

  19. Depleted uranium: A DOE management guide

    SciTech Connect

    1995-10-01

    The U.S. Department of Energy (DOE) has a management challenge and financial liability in the form of 50,000 cylinders containing 555,000 metric tons of depleted uranium hexafluoride (UF{sub 6}) that are stored at the gaseous diffusion plants. The annual storage and maintenance cost is approximately $10 million. This report summarizes several studies undertaken by the DOE Office of Technology Development (OTD) to evaluate options for long-term depleted uranium management. Based on studies conducted to date, the most likely use of the depleted uranium is for shielding of spent nuclear fuel (SNF) or vitrified high-level waste (HLW) containers. The alternative to finding a use for the depleted uranium is disposal as a radioactive waste. Estimated disposal costs, utilizing existing technologies, range between $3.8 and $11.3 billion, depending on factors such as applicability of the Resource Conservation and Recovery Act (RCRA) and the location of the disposal site. The cost of recycling the depleted uranium in a concrete based shielding in SNF/HLW containers, although substantial, is comparable to or less than the cost of disposal. Consequently, the case can be made that if DOE invests in developing depleted uranium shielded containers instead of disposal, a long-term solution to the UF{sub 6} problem is attained at comparable or lower cost than disposal as a waste. Two concepts for depleted uranium storage casks were considered in these studies. The first is based on standard fabrication concepts previously developed for depleted uranium metal. The second converts the UF{sub 6} to an oxide aggregate that is used in concrete to make dry storage casks.

  20. Chronic Δ-9-tetrahydrocannabinol administration increases lymphocyte CXCR4 expression in rhesus macaques.

    PubMed

    LeCapitaine, Nicole J; Zhang, Ping; Winsauer, Peter; Walker, Edith; Vande Stouwe, Curtis; Porretta, Constance; Molina, Patricia E

    2011-12-01

    Cannabinoids have been reported to produce various immunomodulatory effects, which could potentially impact the host response to bacterial or viral infection. We have recently demonstrated that chronic Δ-9-tetrahydrocannabinol (THC; 0.32 mg/kg i.m., BID) decreased early mortality in rhesus macaques infected with simian immunodeficiency virus (SIV). However, the possibility that prolonged THC administration affects lymphocyte counts, phenotype, and proliferation indices has not been addressed. We examined expression of proliferative and phenotypic markers in circulating lymphocytes of male young adult rhesus macaques chronically-treated with THC (i.m. twice daily 0.32 mg/kg) for 12 months. Chronic THC administration did not alter lymphocyte subtypes, naïve and memory subsets, proliferation, or apoptosis of T lymphocytes when compared to time-matched vehicle-treated controls. However, chronic THC increased T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes compared to control. These results show that chronic THC administration produces changes in T cell phenotype, which can potentially contribute to host immunomodulation to infectious challenges.

  1. Anatomy of Depleted Interplanetary Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B., IV

    2017-01-01

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE/SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C6+/C5+ and O7+/O6+ depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  2. Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+) conventional T cells in intestinal tumors.

    PubMed

    Akeus, Paulina; Langenes, Veronica; Kristensen, Jonas; von Mentzer, Astrid; Sparwasser, Tim; Raghavan, Sukanya; Quiding-Järbrink, Marianne

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent tumor types worldwide and tumor-infiltrating T cells are crucial for anti-tumor immunity. We previously demonstrated that Treg cells from CRC patients inhibit transendothelial migration of conventional T cells. However, it remains unclear if local Treg cells affect lymphocyte migration into colonic tumors. By breeding APC(Min/+) mice with depletion of regulatory T cells mice, expressing the diphtheria toxin receptor under the control of the FoxP3 promoter, we were able to selectively deplete Treg cells in tumor-bearing mice, and investigate the impact of these cells on the infiltration of conventional T cells into intestinal tumors. Short-term Treg-cell depletion led to a substantial increase in the frequencies of T cells in the tumors, attributed by both increased infiltration and proliferation of T cells in the Treg-cell-depleted tumors. We also demonstrate a selective increase of the chemokines CXCL9 and CXCL10 in Treg-cell-depleted tumors, which were accompanied by accumulation of CXCR3(+) T cells, and increased IFN-γ mRNA expression. In conclusion, Treg-cell depletion increases the accumulation of conventional T cells in intestinal tumors, and targeting Treg cells could be a possible anti-tumor immunotherapy, which not only affects T-cell effector functions, but also their recruitment to tumors.

  3. Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2014-04-03

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  4. [Laboratory diagnosis of lymphocytic meningitis].

    PubMed

    Marí, José María Navarro; Ruiz, Mercedes Pérez; Anza, Diego Vicente

    2010-01-01

    Lymphocytic meningitis, mainly those with an acute and benign course, are caused by viruses. In our area, the most commonly involved agents are enteroviruses, herpes simplex, varicella zoster and Toscana viruses. Nucleic acids amplification techniques (NAAT) are the methods of choice to diagnose viral meningitis from cerebrospinal fluid (CSF) samples. They are more rapid and sensitive, and indeed, they are not influenced by the viability of the virus in the clinical specimen as traditional methods are. The development of commercial equipments, the degree of automation, and the use of real-time polymerase chain reaction (PCR) systems are the most important premises to choose the molecular method in each laboratory. Recently, commercial kits of real-time PCR are available for the detection of enteroviruses and herpesviruses, which are the most frequently viruses involved in meningitis. Although NAAT from the clinical sample have replaced cell culture for diagnostic purposes, the combination of both methods remain useful. When the detection of the causal agent from the CSF sample is not possible, other specimens (pharyngeal exudates, stools) or serological methods can be used. Serology is the reference method for meningitis caused by West Nile virus and lymphocytic choriomeningitis virus, which are less frequently detected in our area.

  5. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  6. Effects of atomic bomb radiation on the differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes.

    PubMed

    Yamada, Y; Neriishi, S; Ishimaru, T; Shimba, N; Hamilton, H B; Ohgushi, Y; Koyanagi, M; Ichimaru, M

    1985-02-01

    The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC.

  7. B lymphocytes play a limited role in clearance of Campylobacter jejuni from the chicken intestinal tract

    PubMed Central

    Lacharme-Lora, Lizeth; Chaloner, Gemma; Gilroy, Rachel; Humphrey, Suzanne; Gibbs, Kirsty; Jopson, Sue; Wright, Elli; Reid, William; Ketley, Julian; Humphrey, Tom; Williams, Nicola; Rushton, Steven; Wigley, Paul

    2017-01-01

    Campylobacter jejuni is the leading cause of foodborne bacterial gastroenteritis with contaminated poultry meat its main source. Control of C. jejuni is a priority for the poultry industry but no vaccines are available and their development hampered by poor understanding of the immunobiology of C. jejuni infection. Here we show the functional role of B lymphocytes in response to C. jejuni in the chicken through depletion of the B lymphocyte population (bursectomy) followed by challenge. B lymphocyte depletion has little effect on bacterial numbers in the ceca, the main site of colonisation, where C. jejuni persist to beyond commercial slaughter age, but reduces clearance from the small intestine. In longer-term experiments we show antibody leads to reduction in C. jeuni numbers in the ceca by nine weeks post infection. Whilst we did not examine any protective role to re-challenge, it illustrates the difficulty in producing a vaccine in a young, immunologically naïve host. We believe this is first study of functional immunity to C. jejuni in chicken and shows antibody is ineffective in clearing C. jejuni from the ceca within the production lifetime of chickens, although is involved in clearance from the small intestine and longer-term clearance from the ceca. PMID:28332622

  8. Identification and characterization of pro-T lymphocytes and lineage- uncommitted lymphocyte precursors from mice with three novel surface markers

    PubMed Central

    1990-01-01

    The study of prethymic stages of T cell development has been limited because specific markers for mouse pro-T lymphocytes were not available. We developed a panel of rat monoclonal antibodies (mAbs) that bind to our pro-T lymphocyte clones obtained from bone marrow of young adult mice and the thymus of 14-d-old embryos. The mAbs, called Joro 30-8, Joro 37-5, and Joro 75, were found to bind to all pro-T clones tested but not to cell lines representing later stages of T cell development, B lymphocyte, or myeloid lineages. We determined the frequency and tissue distribution in normal and immunodeficient mouse strains as well as the ontogeny in liver and thymus of cells positive for these mAbs. The results were consistent with the pattern of reactivity observed with cell lines. We isolated Joro 30-8+, Joro 37- 5+, and Joro 75+ bone marrow cells by cell sorter and found that: (a) phenotypically, they are Thy-1+, CD4-, CD8-, CD3-, B-220-, IgM-, F4/80- , and PgP-1+; (b) they grew in response to the combination of interleukin 3 (IL-3) + IL-4 or IL-3 + IL-4 + IL-6; and (c) Joro 37-5+ and Joro 75+ marrow cells gave rise to mature T lymphocytes but not to B lymphocytes, while Joro 30-8+ marrow cells generated both T and B lymphocytes after 8-12 wk of transfer into severe combined immunodeficient (Scid) mice. In normal mice subjected to 600 rad of irradiation to induce a wave of thymus recolonization, we found by flow fluorocytometry analysis that Joro+ cells entered the thymus 2 d after irradiation, expanded during the next 4 d, and underwent further differentiation, and from day 8 up to day 21, post-irradiation Joro+ cells were no longer detectable in the thymuses. Immunohistochemical analysis of normal thymus shows the presence of very few Joro 30-8+, Joro 37-5+, and Joro 75+ lymphoid cells in the subcapsular area and outer cortex but not in the medulla. The kinetic analysis of tissue sections from thymuses at various days post-irradiation suggests that Joro+ cells enter

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

    PubMed

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

    2005-02-10

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

  10. Dengue virus-specific murine T-lymphocyte proliferation: serotype specificity and response to recombinant viral proteins.

    PubMed Central

    Rothman, A L; Kurane, I; Zhang, Y M; Lai, C J; Ennis, F A

    1989-01-01

    Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. In this study, we demonstrated that dengue virus-specific T lymphocytes were detected in spleen cells from dengue virus-immune mice using an in vitro proliferation assay. Following immunization with a single dose of infectious dengue virus, murine lymphocytes showed increased proliferation when incubated in the presence of viral antigens of the same serotype but not in the presence of control antigens. Depletion experiments with antibody and complement showed that the population of responding cells expressed the Thy1+ L3T4+ Lyt2- phenotype. This indicates that the predominant proliferating cells are T lymphocytes of the helper-inducer phenotype. Dengue virus-specific memory lymphocyte responses were detectable for at least 22 weeks after immunization. The response to primary infection was primarily serotype specific, with some serotype cross-reactivity present at a low level. We demonstrated that lymphocytes from mice immunized with dengue 4 virus proliferate in response to a combination of dengue 4 virus C, pre-M, E, NS1, and NS2a proteins expressed in Sf9 cells with a recombinant baculovirus, and, to a lesser extent, to the dengue 4 virus E protein alone. PMID:2786087

  11. What Are the Key Statistics for Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... What Are the Key Statistics for Chronic Lymphocytic Leukemia? The American Cancer Society's estimates for leukemia in ... Leukemia Research and Treatment? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  12. Suppression of mixed lymphocyte reactivity by human chorionic gonadotrophin

    PubMed Central

    Beling, C. G.; Weksler, M. E.

    1974-01-01

    Highly purified human chorionic gonadotrophin inhibits the response of lymphocytes from both male and female subjects to allogeneic cells in mixed lymphocyte culture. Human chorionic gonadotrophin is not cytotoxic for human lymphocytes. PMID:4283122

  13. New Approach For Prediction Groundwater Depletion

    NASA Astrophysics Data System (ADS)

    Moustafa, Mahmoud

    2017-01-01

    Current approaches to quantify groundwater depletion involve water balance and satellite gravity. However, the water balance technique includes uncertain estimation of parameters such as evapotranspiration and runoff. The satellite method consumes time and effort. The work reported in this paper proposes using failure theory in a novel way to predict groundwater saturated thickness depletion. An important issue in the failure theory proposed is to determine the failure point (depletion case). The proposed technique uses depth of water as the net result of recharge/discharge processes in the aquifer to calculate remaining saturated thickness resulting from the applied pumping rates in an area to evaluate the groundwater depletion. Two parameters, the Weibull function and Bayes analysis were used to model and analyze collected data from 1962 to 2009. The proposed methodology was tested in a nonrenewable aquifer, with no recharge. Consequently, the continuous decline in water depth has been the main criterion used to estimate the depletion. The value of the proposed approach is to predict the probable effect of the current applied pumping rates on the saturated thickness based on the remaining saturated thickness data. The limitation of the suggested approach is that it assumes the applied management practices are constant during the prediction period. The study predicted that after 300 years there would be an 80% probability of the saturated aquifer which would be expected to be depleted. Lifetime or failure theory can give a simple alternative way to predict the remaining saturated thickness depletion with no time-consuming processes such as the sophisticated software required.

  14. Radiation-induced bystander effect in healthy G(o) human lymphocytes: biological and clinical significance.

    PubMed

    Belloni, Paola; Latini, Paolo; Palitti, Fabrizio

    2011-08-01

    To study the bystander effects, G(0) human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H(2)O(2)) and superoxide anion (O(2)(-)) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  15. CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy.

    PubMed

    Cartwright, Emily K; Spicer, Lori; Smith, S Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O; Nega, Melon; Easley, Kirk; Schmitz, Joern E; Bosinger, Steven E; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H; Estes, Jacob D; Lifson, Jeffrey D; Derdeyn, Cynthia A; Silvestri, Guido

    2016-09-20

    Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.

  16. Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.

    PubMed

    Daly, Eileen; Ecker, Christine; Hallahan, Brian; Deeley, Quinton; Craig, Michael; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Gudbrandsen, Maria; Brammer, Michael; Giampietro, Vincent; Lamar, Melissa; Page, Lisa; Toal, Fiona; Schmitz, Nicole; Cleare, Anthony; Robertson, Dene; Rubia, Katya; Murphy, Declan G M

    2014-09-01

    It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target.

  17. Lymphocyte subpopulations in Sheehan's syndrome.

    PubMed

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

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in

  18. The New MCNP6 Depletion Capability

    SciTech Connect

    Fensin, Michael Lorne; James, Michael R.; Hendricks, John S.; Goorley, John T.

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  19. The new MCNP6 depletion capability

    SciTech Connect

    Fensin, M. L.; James, M. R.; Hendricks, J. S.; Goorley, J. T.

    2012-07-01

    The first MCNP based in-line Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology. (authors)

  20. The selective expression of distinct fucosylated glycoproteins on murine T and B lymphocyte subsets.

    PubMed

    Abdul-Salam, Fatma; Mansour, Mohamed H; Al-Shemary, Tahany

    2005-01-01

    The putative expression of distinct terminally fucosylated glycoconjugates among murine lymphocyte subpopulations was sought using Ulex europaeus agglutinin-I (UEA-I) and Anguilla anguilla agglutinin (AAA), each with a distinctive primary binding preference to type II and type I blood group H oligosaccharide determinants, respectively. In newly born and adult mice, direct labeling of isolated lymphocyte subsets in suspension, as well as immunohistochemical assays were indicative of the age-regulated co-expression of the UEA-I-reactive ligand among thymic epithelial cells and a subset of the mature (PNA-), medullary thymocytes. In the spleen, UEA-I-ligand expression was selectively confined to a subset of the CD4+ T lymphocytes scattered around red pulp sinuses in newly born mice, but distinctively localized within the T cell-dependent periarteriolar lymphoid sheath compartment in adult mice. Among thymocytes of adult mice, two-dimensional Western blots demonstrated the expression of the UEA-I-reactive ligand among multiple isoforms of three major 50, 114 and 180kDa acidic glycoproteins, of which, heterogeneous weight and charge variants of the 114kDa component were also evident among splenocytes. The expression of the AAA-reactive ligand was, on the other hand, restricted to a single major 120 kDa acidic glycoprotein, in addition to a minor molecular weight variant of 115kDa, associated with a subset of immature IgM+ B lymphocytes localized within the red pulp, in both newly born and adult mice. The significance of these findings is discussed in relation to mechanisms that govern lymphocyte maturation, selection and migration.

  1. Lenalidomide and Chronic Lymphocytic Leukemia

    PubMed Central

    González-Rodríguez, Ana Pilar; Payer, Angel R.; Acebes-Huerta, Andrea; Huergo-Zapico, Leticia; Villa-Alvarez, Monica; Gonzalez-García, Esther; Gonzalez, Segundo

    2013-01-01

    Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS) and tumor flare reaction (TFR), that make its management different from other hematologic malignancies. PMID:24163824

  2. Transplantation in chronic lymphocytic leukemia.

    PubMed

    Le Dieu, Rifca; Gribben, John G

    2007-02-01

    Although there have been no randomized trials comparing the outcome of stem cell transplantation (SCT) with standard chemotherapy for patients with chronic lymphocytic leukemia (CLL), increasingly, both autologous and allogeneic SCT approaches are being explored in this disease. Clinical trials have demonstrated that these approaches are feasible, but current data suggest that autologous transplantation is not curative and myeloablative SCT, although offering the potential for cure, is associated with high treatment-related mortality. There is a clear demonstration of a graft-versus-leukemia effect in CLL, with encouraging results seen after SCT with reduced-intensity conditioning. Because no other treatment modalities are currently capable of improving survival in this disease, the treatment of choice for younger patients with poor-risk CLL may well be SCT, but continued enrollment of appropriate patients into well-designed clinical trials is vital to compare advances in SCT with the advances occurring in chemoimmunotherapy in CLL.

  3. Modified lymphocyte response to mitogens after intraperitoneal injection of glycopeptidolipid antigens from Mycobacterium avium complex.

    PubMed Central

    Brownback, P E; Barrow, W W

    1988-01-01

    Intraperitoneal injection of glycopeptidolipid (GPL) antigens from Mycobacterium avium complex serovar 4 resulted in the decreased ability of murine splenic lymphocytes to respond to nonspecific-mitogen-induced blastogenesis when exposed to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Adherent cell depletion and cell mixing experiments with T lymphocytes indicated that macrophages were not a major contributor to the immunosuppression observed in this study. Enumeration of splenic lymphocytes by means of flow-cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies demonstrated that intraperitoneal injection of GPL antigens resulted in a significant decrease in Thy-1+ and Lyt-1+ cells but no change in the numbers of Lyt-2+ cells. Treatment with GPL antigens in vitro affected the ability of splenic mononuclear cells to respond optimally for concanavalin A-induced blastogenesis at 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml and lipopolysaccharide-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. However, in vitro treatment with GPL antigens did not affect phytohemagglutinin-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. These findings suggest that GPL antigens or their metabolites affect lymphocyte function and may be important cofactors in the overall pathogenesis of M. avium complex infections. PMID:3258582

  4. Cell death of bioenergetically compromised and transcriptionally challenged CLL lymphocytes by chlorinated ATP

    PubMed Central

    Balakrishnan, Kumudha; Stellrecht, Christine M.; Genini, Davide; Ayres, Mary; Wierda, William G.; Keating, Michael J.; Leoni, Lorenzo M.; Gandhi, Varsha

    2005-01-01

    Myeloid cell leukemia-1 (MCL-1) acts as a key survival factor for chronic lymphocytic leukemia (CLL) cells. In addition, dissipation of cellular bioenergy may impose a lethal effect on these quiescent cells. Previously, in multiple myeloma cell lines we demonstrated that halogenated adenosine (8-Cl-Ado) was phosphorylated to triphosphate (8-Cl–adenosine triphosphate [ATP]), which preferentially incorporated into mRNA and inhibited RNA synthesis by premature transcription termination. Furthermore, 8-Cl-ATP accumulation was associated with a decline in cellular bioenergy. Based on these actions, we hypothesized that 8-Cl-Ado would be ideal to target CLL lymphocytes. In the present study we demonstrate that leukemic lymphocytes incubated with 8-Cl-Ado display time- and dose-dependent increase in the accumulation of 8-Cl-ATP, with a parallel depletion of the endogenous ATP pool. Inhibition of global RNA synthesis resulted in a significant decline in the expression of transcripts with a short half-life such as MCL1. Consistent to this, protein expression of MCL-1 but not B-cell lymphoma–2 (BCL-2) was decreased. Furthermore, 8-Cl-ATP induced programmed cell death, as suggested by caspases activation, cleavage of caspase 3, and PARP (poly–adenosine diphosphate [ADP]–ribose polymerase), and increased DNA fragmentation. In conclusion, 8-Cl-Ado induces apoptosis in CLL lymphocytes by targeting cellular bioenergy as well as RNA transcription and translation of key survival genes such as MCL1. PMID:15718423

  5. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction.

    PubMed

    Hofmann, Ulrich; Frantz, Stefan

    2015-01-16

    A large body of evidence produced during decades of research indicates that myocardial injury activates innate immunity. On the one hand, innate immunity both aggravates ischemic injury and impedes remodeling after myocardial infarction (MI). On the other hand, innate immunity activation contributes to myocardial healing, as exemplified by monocytes' central role in the formation of a stable scar and protection against intraventricular thrombi after acute infarction. Although innate leukocytes can recognize a wide array of self-antigens via pattern recognition receptors, adaptive immunity activation requires highly specific cooperation between antigen-presenting cells and distinct antigen-specific receptors on lymphocytes. We have only recently begun to examine lymphocyte activation's relationship to adaptive immunity and significance in the context of ischemic myocardial injury. There is some experimental evidence that CD4(+) T-cells contribute to ischemia-reperfusion injury. Several studies have shown that CD4(+) T-cells, especially CD4(+) T-regulatory cells, improve wound healing after MI, whereas depleting B-cells is beneficial post MI. That T-cell activation after MI is induced by T-cell receptor signaling implicates autoantigens that have not yet been identified in this context. Also, the significance of lymphocytes in humans post MI remains unclear, primarily as a result of methodology. This review summarizes current experimental evidence of lymphocytes' activation, functional role, and crosstalk with innate leukocytes in myocardial ischemia-reperfusion injury, wound healing, and remodeling after myocardial infarction.

  6. Lymphocyte-based model systems for allergy research: a historic overview.

    PubMed

    Neunkirchner, Alina; Schmetterer, Klaus G; Pickl, Winfried F

    2014-01-01

    During the last decades, a multitude of studies applying distinct in vitro and in vivo model systems have contributed greatly to our better understanding of the initiation and regulation of inflammatory processes leading to allergic diseases. Over the years, it has become evident that among lymphocytes, not only IgE-producing B cells and allergy-orchestrating CD4(+) helper cells but also cytotoxic CD8(+) T cells, γδ-T cells and innate lymphoid cells, as well as regulatory lymphocytes, might critically shape the immune response towards usually innocuous allergens. In this review, we provide a historic overview of pioneering work leading to the establishment of important lymphocyte-based model systems for allergy research. Moreover, we contrast the original findings with our currently more refined knowledge to appreciate the actual validity of the respective models and to reassess the conclusions obtained from them. Conflicting studies and interpretations are identified and discussed. The tables are intended to provide an easy overview of the field not only for scientists newly entering the field but also for the broader readership interested in updating their knowledge. Along those lines, herein we discuss in vitro and in vivo approaches to the investigation of lymphocyte effector cell activation, polarization and regulation, and describe depletion and adoptive transfer models along with gene knockout and transgenic (tg) methodologies. In addition, novel attempts to establish humanized T cell antigen receptor tg mouse models for allergy research are described and discussed.

  7. Antibacterial activity of neem nanoemulsion and its toxicity assessment on human lymphocytes in vitro.

    PubMed

    Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, R S; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7-1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2-2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes.

  8. Rap1 and its effector RIAM are required for lymphocyte trafficking.

    PubMed

    Su, Wenjuan; Wynne, Joseph; Pinheiro, Elaine M; Strazza, Marianne; Mor, Adam; Montenont, Emilie; Berger, Jeffrey; Paul, David S; Bergmeier, Wolfgang; Gertler, Frank B; Philips, Mark R

    2015-12-17

    Regulation of integrins is critical for lymphocyte adhesion to endothelium and trafficking through secondary lymphoid organs. Inside-out signaling to integrins is mediated by the small GTPase Rap1. Two effectors of Rap1 regulate integrins, RapL and Rap1 interacting adaptor molecule (RIAM). Using mice conditionally deficient in both Rap1a and Rap1b and mice null for RIAM, we show that the Rap1/RIAM module is not required for T- or B-cell development but is essential for efficient adhesion to intercellular adhesion molecule (ICAM) 1 and vascular cell adhesion molecule (VCAM) 1 and for proper trafficking of lymphocytes to secondary lymphoid organs. Interestingly, in RIAM-deficient mice, whereas peripheral lymph nodes (pLNs) were depleted of both B and T cells and recirculating B cells were diminished in the bone barrow (BM), the spleen was hypercellular, albeit with a relative deficiency of marginal zone B cells. The abnormality in lymphocyte trafficking was accompanied by defective humoral immunity to T-cell-dependent antigens. Platelet function was intact in RIAM-deficient animals. These in vivo results confirm a role for RIAM in the regulation of some, but not all, leukocyte integrins and suggest that RIAM-regulated integrin activation is required for trafficking of lymphocytes from blood into pLNs and BM, where relatively high shear forces exist in high endothelial venules and sinusoids, respectively.

  9. Management of chronic lymphocytic leukemia.

    PubMed

    Stilgenbauer, Stephan; Furman, Richard R; Zent, Clive S

    2015-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for "active disease," which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

  10. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    PubMed

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion.

  11. Ozone depletion and chlorine loading potentials

    NASA Technical Reports Server (NTRS)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  12. Self-regulation, ego depletion, and inhibition.

    PubMed

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  13. Neutral depletion and the helicon density limit

    SciTech Connect

    Magee, R. M.; Galante, M. E.; Carr, J. Jr.; Lusk, G.; McCarren, D. W.; Scime, E. E.

    2013-12-15

    It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup −3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 μs. The ionization rate inferred from these data implies that the electron temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.

  14. Mitochondrial Hyperpolarization and ATP Depletion in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Gergely, Peter; Grossman, Craig; Niland, Brian; Puskas, Ferenc; Neupane, Hom; Allam, Fatme; Banki, Katalin; Phillips, Paul E.; Perl, Andras

    2014-01-01

    Objective Peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients exhibit increased spontaneous and diminished activation-induced apoptosis. We tested the hypothesis that key biochemical checkpoints, the mitochondrial transmembrane potential (ΔΨm) and production of reactive oxygen intermediates (ROIs), mediate the imbalance of apoptosis in SLE. Methods We assessed the ΔΨm with potentiometric dyes, measured ROI production with oxidation-sensitive fluorochromes, and monitored cell death by annexin V and propidium iodide staining of lymphocytes, using flow cytometry. Intracellular glutathione levels were measured by high-performance liquid chromatography, while ATP and ADP levels were assessed by the luciferin–luciferase assay. Results Both ΔΨm and ROI production were elevated in the 25 SLE patients compared with the 25 healthy subjects and the 10 rheumatoid arthritis patients. Intracellular glutathione contents were diminished, suggesting increased utilization of reducing equivalents in SLE. H2O2, a precursor of ROIs, increased ΔΨm and caused apoptosis in normal PBLs. In contrast, H2O2-induced apoptosis and ΔΨm elevation were diminished, particularly in T cells, and the rate of necrotic cell death was increased in patients with SLE. The intracellular ATP content and the ATP:ADP ratio were reduced and correlated with the ΔΨm elevation in lupus. CD3:CD28 costimulation led to transient elevation of the ΔΨm, followed by ATP depletion, and sensitization of normal PBLs to H2O2-induced necrosis. Depletion of ATP by oligomycin, an inhibitor of F0F1–ATPase, had similar effects. Conclusion T cell activation and apoptosis are mediated by ΔΨm elevation and increased ROI production. Mitochondrial hyperpolarization and the resultant ATP depletion sensitize T cells for necrosis, which may significantly contribute to inflammation in patients with SLE. PMID:11817589

  15. [Evolution and phylogeny of B lymphocytes].

    PubMed

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

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

  16. Reprogramming T cell Lymphocytes to Induced Pluripotent Stem Cells

    NASA Astrophysics Data System (ADS)

    Bared, Kalia

    The discovery of induced pluripotent stem cells (iPSC) provided a novel technology for the study of development and pharmacology and complement embryonic stem cells (ES) for cell therapy applications. Though iPSC are derived from adult tissue they are comparable to ES cells in their behavior; multi-lineage differentiation and self-renewal. This makes iPSC research appealing because they can be studied in great detail and expanded in culture broadly. Fibroblasts were the first cell type reprogrammed to an iPSC using a retrovirus vector, since then alternative cell types including lymphocytes have been used to generate iPSC. Different types of vectors have also been developed to enhance iPSC formation and quality. However, specific T lymphocyte subsets have not been shown to reprogram to a pluripotent state to date. Here, we proposed to derive iPSC from peripheral blood effector and central memory T cells, reasoning that the resultant iPSC will maintain the epigenetic memory of a T lymphocyte, including the T cell receptor (TCR) gene rearrangement. This epigenetic memory will enable the differentiation and expansion of T cell iPSC into professional T cells containing a specific TCR. These could then be used for cell therapy to target specific antigens, as well as to improve culture techniques to expand T cells in vitro. We studied different gene delivery methods to derive iPSC from different types of T lymphocytes. We assessed the viability of viral transduction using flow cytometry to detect green fluorescent marker contained in the viral construct and quantitative real time polymerase chain reaction (qRT-PCR) to detect Oct4, Klf4, Sox2, and c-Myc gene expression. Our results demonstrate that the Sendai virus construct is the most feasible platform to reprogram T lymphocytes. We anticipate that this platform will provide an efficient and safe approach to derive iPSC from different T cell subsets, including memory T cells.

  17. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  18. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  19. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  20. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  1. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  2. Chylothorax Associated with Chronic Lymphocytic Leukemia

    PubMed Central

    Kohmoto, Osamu; Kawabe, Kazumi; Ono, Hideya; Yanagimoto, Ryuta; Arimoto, Junji; Hatada, Atsutoshi; Suruda, Tadatoshi; Minakata, Yoshiaki

    2016-01-01

    An 80-year-old man who had suffered from chronic lymphocytic leukemia (CLL) and achieved complete remission was admitted to our hospital due to right pleural effusion. Thoracentesis revealed that the effusion was chyle. Lymphoscintigraphy showed an obstruction of the thoracic duct below the sternum. CD45-gated flow cytometry of the pleural effusion showed elevated numbers of CD5- and CD23-positive lymphocytes and a high serum level of soluble interleukin-2 receptor. These results suggested that the chylothorax was caused by the obstruction of the thoracic duct by the sludging of either abnormal lymphocytes of CLL or transformed malignant lymphoma cells. PMID:27980266

  3. Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility.

    PubMed

    Tooley, Aaron J; Gilden, Julia; Jacobelli, Jordan; Beemiller, Peter; Trimble, William S; Kinoshita, Makoto; Krummel, Matthew F

    2009-01-01

    The systems that refine actomyosin forces during motility remain poorly understood. Septins assemble on the T-cell cortex and are enriched at the mid-zone in filaments. Septin knockdown causes membrane blebbing, excess leading-edge protrusions and lengthening of the trailing-edge uropod. The associated loss of rigidity permits motility, but cells become uncoordinated and poorly persistent. This also relieves a previously unrecognized restriction to migration through small pores. Pharmacologically rigidifying cells counteracts this effect, and relieving cytoskeletal rigidity synergizes with septin depletion. These data suggest that septins tune actomyosin forces during motility and probably regulate lymphocyte trafficking in confined tissues.

  4. Dissolution Treatment of Depleted Uranium Waste

    SciTech Connect

    Gates-Anderson, D D; Laue, C A; Fitch, T E

    2004-02-09

    Researchers at LLNL have developed a 3-stage process that converts pyrophoric depleted uranium metal turnings to a solidified final product that can be transported to and buried at a permitted land disposal site. The three process stages are: (1) pretreatment; (2) dissolution; and (3) solidification. Each stage was developed following extensive experimentation. This report presents the results of their experimental studies.

  5. Demonstration of jackhammer incorporating depleted uranium

    SciTech Connect

    Fischer, L E; Hoard, R W; Carter, D L; Saculla, M D; Wilson, G V

    2000-04-01

    The United States Government currently has an abundance of depleted uranium (DU). This surplus of about 1 billion pounds is the result of an enrichment process using gaseous diffusion to produce enriched and depleted uranium. The enriched uranium has been used primarily for either nuclear weapons for the military or nuclear fuel for the commercial power industry. Most of the depleted uranium remains at the enrichment process plants in the form of depleted uranium hexafluoride (DUF{sub 6}). The Department of Energy (DOE) recently began a study to identify possible commercial applications for the surplus material. One of these potential applications is to use the DU in high-density strikers/hammers in pneumatically driven tools, such as jack hammers and piledrivers to improve their impulse performance. The use of DU could potentially increase tunneling velocity and excavation into target materials with improved efficiency. This report describes the efforts undertaken to analyze the particulars of using DU in two specific striking applications: the jackhammer and chipper tool.

  6. Contrasts between Antarctic and Arctic ozone depletion.

    PubMed

    Solomon, Susan; Portmann, Robert W; Thompson, David W J

    2007-01-09

    This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.

  7. Neutral depletion versus repletion due to ionization

    SciTech Connect

    Fruchtman, A.; Makrinich, G.; Raimbault, J.-L.; Liard, L.; Rax, J.-M.; Chabert, P.

    2008-05-15

    Recent theoretical analyses which predicted unexpected effects of neutral depletion in both collisional and collisionless plasmas are reviewed. We focus on the depletion of collisionless neutrals induced by strong ionization of a collisionless plasma and contrast this depletion with the effect of strong ionization on thermalized neutrals. The collisionless plasma is analyzed employing a kinetic description. The collisionless neutrals and the plasma are coupled through volume ionization and wall recombination only. The profiles of density and pressure both of the plasma and of the neutral-gas and the profile of the ionization rate are calculated. It is shown that for collisionless neutrals the ionization results in neutral depletion, while when neutrals are thermalized the ionization induces a maximal neutral-density at the discharge center, which we call neutral repletion. The difference between the two cases stems from the relation between the neutral density and pressure. The pressure of the collisionless neutral-gas turns out to be maximal where its density is minimal, in contrast to the case of a thermalized neutral gas.

  8. Global Warming: Lessons from Ozone Depletion

    ERIC Educational Resources Information Center

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  9. Direct Visualization of an Impurity Depletion Zone

    NASA Technical Reports Server (NTRS)

    Chernov, Alex A.; Garcia-Ruiz, Juan Ma; Thomas, Bill R.

    2000-01-01

    When a crystal incorporates more impurity per unit of its volume than the impurity concentration in solution, the solution in vicinity of the growing crystal is depleted with respect to the impurity I,2. With a stagnant solution, e. g. in microgravity or gels, an impurity depletion zone expands as the crystal grows and results in greater purity in most of the outer portion of the crystal than in the core. Crystallization in gel provides an opportunity to mimic microgravity conditions and visualize the impurity depletion zone. Colorless, transparent apoferritin (M congruent to 450 KDa) crystals were grown in the presence of red holoferritin dimer as a microheterogeneous impurity (M congruent to 900 KDa) within agarose gel by counterdiffusion with Cd(2+) precipitant. Preferential trapping of dimers, (distribution coefficient K = 4 (exp 1,2)) results in weaker red color around the crystals grown in the left tube in the figure as compared to the control middle tube without crystals. The left and the middle tubes contain colored ferritin dimers, the right tube contains colored trimers. The meniscus in the left tube separate gel (below) and liquid solution containing Cd(2+) (above). Similar solutions, though without precipitants, were present on top of the middle and right tube allowing diffusion of dimers and trimers. The area of weaker color intensity around crystals directly demonstrates overlapped impurity depletion zones.

  10. Maternal cigarette smoking and its effect on neonatal lymphocyte subpopulations and replication

    PubMed Central

    2013-01-01

    Background Significant immunomodulatory effects have been described as result of cigarette smoking in adults and pregnant women. However, the effect of cigarette smoking during pregnancy on the lymphocyte subpopulations in newborns has been discussed, controversially. Methods In a prospective birth cohort, we analyzed the peripheral lymphocyte subpopulations of smoking (SM) and non-smoking mothers (NSM) and their newborns and the replicative history of neonatal, mostly naive CD4 + CD45RA + T cells by measurements of T-cell-receptor-excision-circles (TRECs), relative telomere lengths (RTL) and the serum cytokine concentrations. Results SM had higher lymphocyte counts than NSM. Comparing SM and NSM and SM newborns with NSM newborns, no significant differences in proportions of lymphocyte subpopulations were seen. Regardless of their smoking habits, mothers had significantly lower naive T cells and higher memory and effector T cells than newborns. NSM had significantly lower percentages of CD4 + CD25++ T cells compared to their newborns, which was not significant in SM. There were no differences regarding cytokine concentrations in newborns of SM and NSM. However, NSM had significantly higher Interleukin-7 concentrations than their newborns. Regardless of smoking habits of mothers, newborns had significantly longer telomeres and higher TRECs than their mothers. Newborns of SM had significantly longer telomeres than newborns of NSM. Conclusions Apart from higher lymphocyte counts in SM, our results did not reveal differences between lymphocyte subpopulations of SM and NSM and their newborns, respectively. Our finding of significantly longer RTL in newborns of SM may reflect potential harm on lymphocytes, such as cytogenetic damage induced by smoking. PMID:23597118

  11. Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease.

    PubMed

    Chiang, Eugene Y; Kolumam, Ganesh A; Yu, Xin; Francesco, Michelle; Ivelja, Sinisa; Peng, Ivan; Gribling, Peter; Shu, Jean; Lee, Wyne P; Refino, Canio J; Balazs, Mercedesz; Paler-Martinez, Andres; Nguyen, Allen; Young, Judy; Barck, Kai H; Carano, Richard A D; Ferrando, Ron; Diehl, Lauri; Chatterjea, Devavani; Grogan, Jane L

    2009-07-01

    Uncontrolled T helper type 1 (T(H)1) and T(H)17 cells are associated with autoimmune responses. We identify surface lymphotoxin-alpha (LT-alpha) as common to T(H)0, T(H)1 and T(H)17 cells and employ a unique strategy to target these subsets using a depleting monoclonal antibody (mAb) directed to surface LT-alpha. Depleting LT-alpha-specific mAb inhibited T cell-mediated models of delayed-type hypersensitivity and experimental autoimmune encephalomyelitis. In collagen-induced arthritis (CIA), preventive and therapeutic administration of LT-alpha-specific mAb inhibited disease, and immunoablated T cells expressing interleukin-17 (IL-17), interferon-gamma and tumor necrosis factor-alpha (TNF-alpha), whereas decoy lymphotoxin-beta receptor (LT-betaR) fusion protein had no effect. A mutation in the Fc tail, rendering the antibody incapable of Fcgamma receptor binding and antibody-dependent cellular cytotoxicity activity, abolished all in vivo effects. Efficacy in CIA was preceded by a loss of rheumatoid-associated cytokines IL-6, IL-1beta and TNF-alpha within joints. These data indicate that depleting LT-alpha-expressing lymphocytes with LT-alpha-specific mAb may be beneficial in the treatment of autoimmune disease.

  12. How Depleted is the MORB mantle?

    NASA Astrophysics Data System (ADS)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  13. 21 CFR 864.8500 - Lymphocyte separation medium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  14. 21 CFR 864.8500 - Lymphocyte separation medium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  15. 21 CFR 864.8500 - Lymphocyte separation medium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  16. 21 CFR 864.8500 - Lymphocyte separation medium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  17. 21 CFR 864.8500 - Lymphocyte separation medium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  18. Adenovirus-receptor interaction with human lymphocytes.

    PubMed

    Mentel, R; Döpping, G; Wegner, U; Seidel, W; Liebermann, H; Döhner, L

    1997-03-01

    Lymphocytes play a key role in cell-mediated immunity and are host cells for several viral and bacterial pathogens. Their importance in adenovirus (Ad) infections is not yet fully understood. The initial event, the attachment of Ad to lymphocytes and their subsets, was examined using flow cytometry. The study included analysis of stimulated T cells in binding assays with FITC-labeled Ad fiber. The results confirm that native peripheral lymphocytes express very small amounts of Ad receptors. Stimulation with PHA and interleukin 2 induced the expression. The presence of Ad DNA as a sign of internalization in stimulated cells was demonstrated using the polymerase chain reaction. The findings suggest that lymphocytes after stimulation can turn into target cells for Ad. This is particularly important if there are indications for persistence of Ad, and in the case of immunocompromised patients severe, life-threatening diseases can develop.

  19. T-lymphocyte subpopulations in uveitis.

    PubMed Central

    Murray, P. I.; Dinning, W. J.; Rahi, A. H.

    1984-01-01

    Following an inconclusive study of differential lymphocyte counts in uveitis in which the peripheral blood was examined only once in the course of each case a longitudinal study has been carried out in patients with acute anterior uveitis. Venous blood lymphocytes were examined at intervals throughout the course of the illness, from presentation until six months later. No changes in E-rosetting T cells or total lymphocyte values have been found, nor any variations from normal in the helper (OKT4)/suppressor (OKT8) T-cell ratio. Random studies performed in a sample of patients with heterochromic cyclitis have also failed to reveal consistent abnormalities in peripheral blood lymphocyte parameters. PMID:6236843

  20. Monoclonal antibodies in chronic lymphocytic leukemia.

    PubMed

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

    2006-09-01

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

  1. Lymphocyte populations in acute viral gastroenteritis.

    PubMed Central

    Dolin, R; Reichman, R C; Fauci, A S

    1976-01-01

    Viral gastroenteritis was induced in 16 of 24 normal volunteers after oral administration of either the Norwalk or Hawaii agents. Clinical illness lasted for 24 to 48 h and resolved spontaneously. During acute illness, a transient lymphopenia was noted which involved all lymphocyte subpopulations (thymus-and bone marrow-derived, and null cells). No circulating lymphocytotoxins were detected, and the lymphocytes remaining in the circulation responded normally to mitogenic stimuli. The acute lymphopenia occurred at the time that mononuclear cell infiltration of the jejunal mucosa has been noted. These findings are consistent with the occurrence of a redistribution of circulating lymphocytes during acute illness, with accumulation of lymphocytes at the site of infection in the gut. PMID:1085751

  2. Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism

    PubMed Central

    Liu, Jinyun; Chen, Gang; Pelicano, Helene; Liao, Jianwei; Huang, Jie; Feng, Li; Keating, Michael J.; Huang, Peng

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Loss of p53 function in CLL cells due to chromosome 17p deletion or p53 mutations often leads to a more malignant disease phenotype and is associated with drug resistance and poor clinical outcome. Thus, development of novel therapeutic strategies to effectively target CLL cells with p53 deficiency is clinically important. Here we showed that p53-null CLL cells were highly sensitive to ROS-mediated cell killing due to their intrinsic ROS stress. We further demonstrated that a natural compound phenethyl isothiocyanate (PEITC) was able to effectively kill CLL cells with loss of p53, even under the protection of stromal cells. In p53-defficient CLL cells, PEITC induced a rapid depletion of glutathione and a severe accumulation of ROS, leading to massive leukemia cell death in the stromal microenvironment. The drug-induced cell death was associated with a significant decrease of in MCL-1 survival molecule. We further showed that ROS-mediated cell death was the key mechanism by which PEITC induced cytotoxicity, since such cell death could be prevented by addition of antioxidant NAC. Importantly, in vivo study showed that PEITC was able to induce substantial leukemia cell death in mice. Treatment of CLL mice harboring TCL1-Tg:p53−/− genotype with PEITC significantly prolonged the median survival time of the animals. Our study identifies a vulnerability of p53-null CLL cells with high sensitivity to ROS-generating agents, and suggests that PEITC may potentially be useful for clinical treatment of CLL with 17p deletion and p53 mutations. PMID:27655686

  3. Reed-Sternberg/lymphocyte rosette: lymphocyte subpopulations as defined by monoclonal antibodies.

    PubMed Central

    Morris, C S; Stuart, A E

    1984-01-01

    The Reed-Sternberg cell/lymphocyte rosette characteristic of Hodgkin's disease tissue and cell suspensions was investigated with monoclonal antibodies on fresh viable cell suspensions prepared from nine cases of Hodgkin's disease. The biopsy material comprised six spleens and three lymph nodes. The majority of the rosetting lymphocytes were T cells, primarily of the helper subset. Some of the attached lymphocytes were suppressor T cells. In addition, a few of the rosetting lymphocytes around Reed-Sternberg cells were B cells. Images PMID:6378976

  4. Role of yessotoxin in calcium and cAMP-crosstalks in primary and K-562 human lymphocytes: the effect is mediated by anchor kinase A mitochondrial proteins.

    PubMed

    Tobío, Araceli; Fernández-Araujo, Andrea; Alfonso, Amparo; Botana, Luis M

    2012-12-01

    Yessotoxin (YTX) is a marine polyether toxin previously described as a phosphodiesterase (PDE) activator in fresh human lymphocytes. This toxin induces a decrease of adenosine 3',5'-cyclic monophosphate (cAMP) levels in fresh human lymphocytes in a medium with calcium (Ca(2+) ), whereas the contrary effect has been observed in a Ca(2+) -free medium. In the present article, the effect of YTX in K-562 lymphocytes cell line has been analysed. Surprisingly, results obtained in K-562 cell line are completely opposite than in fresh human lymphocytes, since in K-562 cells YTX induces an increase of cAMP levels. YTX cytotoxicity was also studied in both K-562 cell line and fresh human lymphocytes. Results demonstrate that YTX does not modify fresh human lymphocytes viability, whereas in K-562 cells, YTX has a highly cytotoxic effect. It has been described in a previous study that YTX induces a small cytosolic Ca(2+) increase in fresh human lymphocytes but no effect was observed on Ca(2+) pools depletion in these cells. However, our results show that, in K-562 cells, YTX has no effect on cytosolic Ca(2+) levels in a medium with Ca(2+) and induces an increase on Ca(2+) pools depletion followed by a Ca(2+) influx. As far as Ca(2+) modulation is concerned these results demonstrate that YTX has a clear opposite effect in tumoural and fresh human lymphocytes. In addition, intracellular Ca(2+) reservoirs affected by YTX are different than thapsigargin-sensible pools. Furthermore, YTX-dependent Ca(2+) pools depletion was abolished by cAMP analogue (dibutyryl cAMP), phosphodiesterase-4 (PDE4) inhibitor (rolipram), protein kinase A inhibitor (H89) and oxidative phosphorylation uncoupler carbonyl cyanide p-(trifluoromethoxy) (FCCP) treatments. This evidences the crosstalks between Ca(2+) , YTX and cAMP pathways. Also, results obtain demonstrate that YTX-dependent Ca(2+) influx was only abolished by FCCP pre-treatment, which indicates a link between YTX and mitochondria in K-562 cell

  5. Chemotaxis of large granular lymphocytes

    SciTech Connect

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

    1986-01-01

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-..beta.. 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/sup +/ 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 ..mu..m 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(/sup 3/H)P, suggesting that LGL bear receptors for the chemotactic peptide.

  6. How T lymphocytes see antigen

    NASA Astrophysics Data System (ADS)

    Chakraborty, Arup K.

    2009-03-01

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

  7. Obinutuzumab for chronic lymphocytic leukemia.

    PubMed

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

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

  8. Indium 111 toxicity in the human lymphocyte

    SciTech Connect

    Silberstein, E.B.; Watson, S.; Mayfield, G.; Kereiakes, J.G.; Bullock, W.

    1985-05-01

    Indium-labeled lymphocytes were examined for response to a variety of mitogens, ability to synthesize immunoglobulins, mitotic index, and presence of chromosome aberrations at a range of exposures from 0.2 to 500 muCi/10(8) cells. Results of all four tests were found to be abnormal when the lymphocytes were labeled with /sup 111/In activities well within those employed for diagnostic testing.

  9. T and B lymphocytes in myasthenia gravis.

    PubMed Central

    Itoyama, Y; Kawanami, S; Goto, I; Kuroiwa, Y

    1979-01-01

    Peripheral blood lymphocytes from seventeen non-thymectomized and nine thymectomized patients with myasthenia gravis (MG) and thirteen healthy controls were examined for the presence of surface markers characteristic of T and B lymphocytes by rosette formation with sheep red blood cells (SRBC). T cells were identified by their capacity to spontaneously form rosettes with SRBCs. The percentage of B lymphocytes was determined by the erythrocyte antibody complement (EAC) rosette-forming test. The EAC complex was prepared with either whole rabbit anti-SRBC serum or with the IgM fraction of rabbit anti-SRBC serum. The two kind of erythrocyte complement rosette-forming cells (EAC-RFC) are designated erythrocyte-haemolysin-complement RFC (EA(H)C-RFC), and erythrocyte-IgM-complement RFC (EA(M)C-RFC). The percentage of total lymphocytes and T cells was not altered in MG patients. The percentage of 'active' T cells, which have been considered to be more actively involved in cellular immunity, was also similar in MG patients and controls. A significant increase in EA(H)C-RFC occurred in both thymectomized and non-thymectomized MG patients, while in B cells detected by EA(M)C-RFC no alterations were found. The increase in EA(H)C-RFC in lymphocytes from MG patients may be due to an increase in the 19S antibody-forming B lymphocytes or to an increase in T cells which have Fc receptors on their surface. PMID:315844

  10. Effects of isolation on various lymphocyte activities

    SciTech Connect

    Jessop, J.J.

    1986-01-01

    Prolonged exposure of Sprague Dawley male rats to isolation, water scheduling, or their combination resulted in an enhanced lymphocyte proliferative response to mitogen. Time course studies of effects of isolation on mitogenic response of splenic and/or blood T and B lymphocytes and splenic NK cell activity demonstrated a suppression with short term exposure followed by an enhancement with prolonged exposure. Use of immunoperoxidase staining techniques to identify splenic T or T helper cells revealed that prolonged exposure to isolation had no significant effect on the proportion of these cell populations in the spleen. Examination of the data by Lineweaver-Burke plot and plot of the data as % maximum response showed that prolonged exposure to isolation did not alter the sensitivity of the lymphocytes to mitogen. Involvement of corticosteroids and opioid peptides in mediation of the effects of exposure to isolation on lymphocyte activity was assessed by measurement of plasma corticosterone by radioimmunoassay and by examination of the ability of the opioid antagonist naltrexone to alter the effects of isolation on lymphocyte proliferative response to mitogen. Attempts were made to mimic the effects of short-term isolation on lymphocyte activity by morphine sulfate administration.

  11. Immunoregulatory effects of morphine on human lymphocytes.

    PubMed Central

    Nair, M P; Schwartz, S A; Polasani, R; Hou, J; Sweet, A; Chadha, K C

    1997-01-01

    It is now well established that parenteral drug abuse is a significant risk factor for contracting human immunodeficiency virus type 1 (HIV-1) infection and subsequently developing AIDS. Earlier studies have shown that morphine can modulate various immune responses and therefore support the premise that morphine is a cofactor in susceptibility to and progression of HIV infection. Dysregulation of interferon (IFN) production, nonspecific apoptosis of T cells, and the immune response to soluble HIV gene products have been associated with potential mechanisms of pathogenesis in HIV disease. The present study was undertaken to examine the immunomodulatory role of morphine on HIV protein-induced lymphocyte proliferative responses, Sendai and Newcastle disease virus-induced alpha IFN (IFN-alpha) and IFN-beta production by lymphocytes and fibroblast cells, respectively, and induction of apoptosis of normal lymphocytes in vitro. Our results demonstrate that HIV protein-induced human lymphocyte proliferative responses were significantly inhibited by morphine in a dose-dependent manner. Furthermore, morphine significantly inhibited both IFN-alpha and IFN-beta production by normal lymphocytes and fibroblasts but induced apoptosis of normal lymphocytes. Inhibition of IFN-alpha production by morphine could be reversed by the opiate receptor antagonist naloxone. This suggests that the immunomodulatory effects of morphine are mediated through the opioid receptor. These studies support a role of morphine as a cofactor in the pathogenesis of HIV infection and describe some of the possible pathologic mechanisms which underlie the immunoregulatory effects of morphine. PMID:9067644

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

    ClinicalTrials.gov

    2017-03-24

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

  13. Aquaporin 2-labeled cells differentiate to intercalated cells in response to potassium depletion.

    PubMed

    Kim, Wan-Young; Nam, Sun Ah; Choi, Arum; Kim, Yu-Mi; Park, Sang Hee; Kim, Yong Kyun; Kim, Jin

    2016-01-01

    The mammalian renal collecting duct consists of principal cells (PCs) and intercalated cells (ICs). Both PCs and ICs are involved in potassium (K(+)) homeostasis, PCs through their role in K(+) secretion and ICs through their ability to facilitate K(+) resorption. We previously hypothesized that PCs may differentiate into ICs upon K(+) depletion. However, no direct evidence has yet been obtained to conclusively demonstrate that PCs differentiate into ICs in response to K(+) depletion. Here, we present direct evidence for the differentiation of PCs into ICs by cell lineage tracing using aquaporin 2 (AQP2)-Cre mice and R26R-EYFP transgenic mice. In control mice, AQP2-EYFP(+) cells exhibited mainly a PC phenotype (AQP2-positive/H(+)-ATPase-negative). Interestingly, some AQP2-EYFP(+) cells exhibited an IC phenotype (H(+)-ATPase-positive/AQP2-negative); these cells accounted for 1.7 %. After K(+) depletion, the proportion of AQP2-EYFP(+) cells with an IC phenotype was increased to 4.1 %. Furthermore, some AQP2-EYFP(+) cells exhibited a "null cell" phenotype (AQP2-negative/H(+)-ATPase-negative) after K(+) depletion. Collectively, our data demonstrate that AQP2-labeled cells can differentiate into ICs, as well as null cells, in response to K(+) depletion. This finding indicates that some of AQP2-labeled cells possess properties of progenitor cells and that they can differentiate into ICs in the adult mouse kidney.

  14. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    ClinicalTrials.gov

    2016-10-24

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Iron isotope composition of depleted MORB

    NASA Astrophysics Data System (ADS)

    Labidi, J.; Sio, C. K. I.; Shahar, A.

    2015-12-01

    In terrestrial basalts, iron isotope ratios are observed to weakly fractionate as a function of olivine and pyroxene crystallization. However, a ~0.1‰ difference between chondrites and MORB had been reported (Dauphas et al. 2009, Teng et al. 2013 and ref. therein). This observation could illustrate an isotope fractionation occurring during partial melting, as a function of the Fe valence in melt versus crystals. Here, we present high-precision Fe isotopic data measured by MC-ICP-MS on well-characterized samples from the Pacific-Antarctic Ridge (PAR, n=9) and from the Garrett Transform Fault (n=8). These samples allow exploring the Fe isotope fractionation between melt and magnetite, and the role of partial melting on Fe isotope fractionation. Our average δ56Fe value is +0.095±0.013‰ (95% confidence, n=17), indistinguishable from a previous estimate of +0.105±0.006‰ (95% confidence, n=43, see ref. 2). Our δ56Fe values correlate weakly with MgO contents, and correlate positively with K/Ti ratios. PAC1 DR10 shows the largest Ti and Fe depletion after titanomagnetite fractionation, with a δ56Fe value of +0.076±0.036‰. This is ~0.05‰ below other samples at a given MgO. This may illustrate a significant Fe isotope fractionation between the melt and titanomagnetite, in agreement with experimental determination (Shahar et al. 2008). GN09-02, the most incompatible-element depleted sample, has a δ56Fe value of 0.037±0.020‰. This is the lowest high-precision δ56Fe value recorded for a MORB worldwide. This basalt displays an incompatible-element depletion consistent with re-melting beneath the transform fault of mantle source that was depleted during a first melting event, beneath the ridge axis (Wendt et al. 1999). The Fe isotope observation could indicate that its mantle source underwent 56Fe depletion after a first melting event. It could alternatively indicate a lower Fe isotope fractionation during re-melting, if the source was depleted of its Fe3

  16. Cytotoxic effector cell granules recognized by the monoclonal antibody TIA-1 are present in CD8+ lymphocytes in lymph nodes of human immunodeficiency virus-1-infected patients.

    PubMed Central

    Tenner-Racz, K.; Racz, P.; Thomé, C.; Meyer, C. G.; Anderson, P. J.; Schlossman, S. F.; Letvin, N. L.

    1993-01-01

    A novel monoclonal antibody (mAB) TIA-1, which recognizes a 15-kd granule-associated protein of cytotoxic T lymphocytes and natural killer cells, has been applied to sections of lymph nodes with human immunodeficiency virus (HIV)-induced lymphadenopathy (follicular hyperplasia and lymphocyte depletion). The protein recognized by this mAB induces apoptosis in permeabilized lymphocytes in vitro. While this mAB reacted with approximately 46% of paracortical CD8+ cells in control nodes, it reacted with 75% of such cells in HIV-induced follicular hyperplasia. Germinal centers of the control nodes contained few TIA-1 + cells; in follicular hyperplasia caused by HIV-1, almost all germinal center CD8+ cells were TIA-1 +. Both in the control nodes and in HIV-induced follicular hyperplasia the majority of TIA-1 + cells coexpressed CD45R0. A marked loss of CD8+TIA-1+ cells was seen in lymphocyte-depleted nodes of patients with AIDS. The loss of these cytotoxic T lymphocytes may have a significant impact on the progression of the disease. Images Figure 1 Figure 2 Figure 3 PMID:8506945

  17. Prolongation of GFP-expressed skin graft after intrathymic injection of GFP positive splenocytes in adult rat

    NASA Astrophysics Data System (ADS)

    Hakamata, Yoji; Igarashi, Yuka; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    GFP is a fluorescent product of the jellyfish Aequorea victoria and has been used for a variety of biological experiments as a reporter molecule. While GFP possesses advantages for the non-invasive imaging of viable cells, GFP-positive cells are still considered potential xeno-antigens. It is difficult to observe the precise fate of transplanted cells/organs in recipients without immunological control. The aim of this study was to determine whether intrathymic injection of GFP to recipients and the depletion of peripheral lymphocytes could lead to donor-specific unresponsiveness to GFP-expressed cell. LEW rats were administered intraperitoneally with 0.2 ml of anti-rat lymphocyte serum (ALS) 1 day prior to intrathymic injection of donor splenocytes or adeno-GFP vector. Donor cells and vector were non-invasively inoculated into the thymus under high frequency ultrasound imaging using an echo-guide. All animals subsequently received a 7 days GFP-expressed skin graft from the same genetic background GFP LEW transgenic rat. Skin graft survival was greater in rats injected with donor splenocytes (23.6+/-9.1) compared with adeno-GFP (13.0+/-3.7) or untreated control rats (9.5+/-1.0). Intrathymic injection of donor antigen into adult rats can induce donor-specific unresponsiveness. Donor cells can be observed for a long-term in recipients with normal immunity using this strategy.

  18. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

    SciTech Connect

    Shudo, Emi; Ribeiro, Ruy M; Perelson, Alan S

    2008-01-01

    While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

  19. Bovine lymphocytes: recognition of cells forming spontaneous (E) rosettes.

    PubMed Central

    Higgins, D A; Stack, M J

    1977-01-01

    About 20% of thymus lymphocytes from neonatal calves formed spontaneous (E) rosettes with SRBCs in medium consisting of 50-100% foetal calf serum (FCS); other media were less satisfactory. FCS was necessary both to allow rosette formation to occur and to maintain stability of the rosettes once formed. Rosettes were stable at 0 degrees C but unstable at 18 degrees C and 37 degrees C. Dead thymus cell (sodium azide treated) did not form rosettes. Treatment of thymus cells with antiserum to bovine Ig-inhibited rosette formation, but this inhibition was considered non-specific since it also occurred with normal rabbit serum. Treatment of SRBCs with neuraminidase slightly enhanced rosette formation by thymus cells, but did not induce peripheral blood lymphocytes to form rosettes. Rosette formation did not occur under a variety of conditions with normal or neuraminidase-treated human, horse, pig, rabbit, guinea-pig, chicken or autologous RBCs. SRBC rosette forming cells were also found in lymph nodes (2-14%) and spleen (less than 5%), but rarely or never in peripheral blood and bone marrow of calves and adults. In foetuses at 80 days of gestation, 49% of thymus cells formed E rosettes. Foetal lymph node cells formed E rosettes at 160 days and spleen at 180 days. Cells with membrane-bound Ig were observed by IFT; their distribution did not coincide with the occurrence of E rosettes. E-rosette formation might be a marker for a subpopulation of bovine T cells. PMID:321167

  20. Copenhagen delegates advance phaseout of ozone depleters

    SciTech Connect

    Kirschner, E.

    1992-12-09

    As expected, delegates at the United Nations Ozone Layer Conference in Copenhagen sped up ozone depleter phaseouts from the 1987 Montreal Protocol and the 1990 London amendments. The changes bring the worldwide production phaseout of chlorofluorocarbons (CFCs) and other ozone depleters in developed countries in line with U.S. and European plans announced earlier this year. Adjustments to the protocol, which are binding on the signatories, change the phaseout for CFC, carbon tetrachloride, and methyl chloroform production and consumption to January 1, 1996 from 2000. The 75% reduction of 1986 levels from CFCs by January 1, 1994 is a compromise between European pressure for an 85% cut and the US goal of 70%. Halon production is to end January 1, 1994, as anticipated. Developing countries continue to have a 10-year grace period. Friends of the Earth ozone campaign director Liz Cook counters that the phaseout dates were scheduled with concern for the chemical industry, not for the ozone layer.

  1. Endoplasmic-Reticulum Calcium Depletion and Disease

    PubMed Central

    Mekahli, Djalila; Bultynck, Geert; Parys, Jan B.; De Smedt, Humbert; Missiaen, Ludwig

    2011-01-01

    The endoplasmic reticulum (ER) as an intracellular Ca2+ store not only sets up cytosolic Ca2+ signals, but, among other functions, also assembles and folds newly synthesized proteins. Alterations in ER homeostasis, including severe Ca2+ depletion, are an upstream event in the pathophysiology of many diseases. On the one hand, insufficient release of activator Ca2+ may no longer sustain essential cell functions. On the other hand, loss of luminal Ca2+ causes ER stress and activates an unfolded protein response, which, depending on the duration and severity of the stress, can reestablish normal ER function or lead to cell death. We will review these various diseases by mainly focusing on the mechanisms that cause ER Ca2+ depletion. PMID:21441595

  2. Ozone depletion in tropospheric volcanic plumes

    NASA Astrophysics Data System (ADS)

    Vance, Alan; McGonigle, Andrew J. S.; Aiuppa, Alessandro; Stith, Jeffrey L.; Turnbull, Kate; von Glasow, Roland

    2010-11-01

    We measured ozone (O3) concentrations in the atmospheric plumes of the volcanoes St. Augustine (1976), Mt. Etna (2004, 2009) and Eyjafjallajökull (2010) and found O3 to be strongly depleted compared to the background at each volcano. At Mt. Etna O3 was depleted within tens of seconds from the crater, the age of the St. Augustine plumes was on the order of hours, whereas the O3 destruction in the plume of Eyjafjallajökull was maintained in 1-9 day old plumes. The most likely cause for this O3 destruction are catalytic bromine reactions as suggested by a model that manages to reproduce the very early destruction of O3 but also shows that O3 destruction is ongoing for several days. Given the observed rapid and sustained destruction of O3, heterogeneous loss of O3 on ash is unlikely to be important.

  3. Replacements For Ozone-Depleting Foaming Agents

    NASA Technical Reports Server (NTRS)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  4. Depleted uranium plasma reduction system study

    SciTech Connect

    Rekemeyer, P.; Feizollahi, F.; Quapp, W.J.; Brown, B.W.

    1994-12-01

    A system life-cycle cost study was conducted of a preliminary design concept for a plasma reduction process for converting depleted uranium to uranium metal and anhydrous HF. The plasma-based process is expected to offer significant economic and environmental advantages over present technology. Depleted Uranium is currently stored in the form of solid UF{sub 6}, of which approximately 575,000 metric tons is stored at three locations in the U.S. The proposed system is preconceptual in nature, but includes all necessary processing equipment and facilities to perform the process. The study has identified total processing cost of approximately $3.00/kg of UF{sub 6} processed. Based on the results of this study, the development of a laboratory-scale system (1 kg/h throughput of UF6) is warranted. Further scaling of the process to pilot scale will be determined after laboratory testing is complete.

  5. Aerobic glycolysis and lymphocyte transformation

    PubMed Central

    Hume, David A.; Radik, Judith L.; Ferber, Ernst; Weidemann, Maurice J.

    1978-01-01

    1. The role of enhanced aerobic glycolysis in the transformation of rat thymocytes by concanavalin A has been investigated. Concanavalin A addition doubled [U-14C]glucose uptake by rat thymocytes over 3h and caused an equivalent increased incorporation into protein, lipids and RNA. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused a specific increase in pyruvate oxidation, leading to an increase in the percentage contribution of glucose to the respiratory fuel. 2. Acetoacetate metabolism, which was not affected by concanavalin A, strongly suppressed pyruvate oxidation in the presence of [U-14C]glucose, but did not prevent the concanavalin A-induced stimulation of this process. Glucose uptake was not affected by acetoacetate in the presence or absence of concanavalin A, but in each case acetoacetate increased the percentage of glucose uptake accounted for by lactate production. 3. [3H]Thymidine incorporation into DNA in concanavalin A-treated thymocyte cultures was sensitive to the glucose concentration in the medium in a biphasic manner. Very low concentrations of glucose (25μm) stimulated DNA synthesis half-maximally, but maximum [3H]thymidine incorporation was observed only when the glucose concentration was raised to 1mm. Lactate addition did not alter the sensitivity of [3H]-thymidine uptake to glucose, but inosine blocked the effect of added glucose and strongly inhibited DNA synthesis. 4. It is suggested that the major function of enhanced aerobic glycolysis in transforming lymphocytes is to maintain higher steady-state amounts of glycolytic intermediates to act as precursors for macromolecule synthesis. PMID:310305

  6. The ultimate disposition of depleted uranium

    SciTech Connect

    Lemons, T.R.

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  7. Alternatives for Disposal of Depleted Uranium Waste.

    DTIC Science & Technology

    1985-11-01

    originating activity by DTIC. Address your request for additional copies to: Defense Technical Information Center Cameron Station Alexandria, Virginia 22314 0...LIST OF TABLES Table Title Page 1 Specific Activity of Depleted Uranium Sand Mixture ......... .................. 8 2 Disposal at Department of Energy...exceed the allowable limits for on-site disposal. This material must be disposed of at a commercial low-level radio- active waste disposal site. Because

  8. Carbon sequestration in depleted oil shale deposits

    DOEpatents

    Burnham, Alan K; Carroll, Susan A

    2014-12-02

    A method and apparatus are described for sequestering carbon dioxide underground by mineralizing the carbon dioxide with coinjected fluids and minerals remaining from the extraction shale oil. In one embodiment, the oil shale of an illite-rich oil shale is heated to pyrolyze the shale underground, and carbon dioxide is provided to the remaining depleted oil shale while at an elevated temperature. Conditions are sufficient to mineralize the carbon dioxide.

  9. The ultimate disposition of depleted uranium

    SciTech Connect

    Not Available

    1990-12-01

    Significant amounts of the depleted uranium (DU) created by past uranium enrichment activities have been sold, disposed of commercially, or utilized by defense programs. In recent years, however, the demand for DU has become quite small compared to quantities available, and within the US Department of Energy (DOE) there is concern for any risks and/or cost liabilities that might be associated with the ever-growing inventory of this material. As a result, Martin Marietta Energy Systems, Inc. (Energy Systems), was asked to review options and to develop a comprehensive plan for inventory management and the ultimate disposition of DU accumulated at the gaseous diffusion plants (GDPs). An Energy Systems task team, under the chairmanship of T. R. Lemons, was formed in late 1989 to provide advice and guidance for this task. This report reviews options and recommends actions and objectives in the management of working inventories of partially depleted feed (PDF) materials and for the ultimate disposition of fully depleted uranium (FDU). Actions that should be considered are as follows. (1) Inspect UF{sub 6} cylinders on a semiannual basis. (2) Upgrade cylinder maintenance and storage yards. (3) Convert FDU to U{sub 3}O{sub 8} for long-term storage or disposal. This will include provisions for partial recovery of costs to offset those associated with DU inventory management and the ultimate disposal of FDU. Another recommendation is to drop the term tails'' in favor of depleted uranium'' or DU'' because the tails'' label implies that it is waste.'' 13 refs.

  10. Depletion modeling of liquid dominated geothermal reservoirs

    SciTech Connect

    Olsen, G.

    1984-06-01

    Depletion models for liquid-dominated geothermal reservoirs are derived and presented. The depletion models are divided into two categories: confined and unconfined. For both cases depletion models with no recharge (or influx), and depletion models including recharge, are used to match field data from the Svartsengi high temperature geothermal field in Iceland. The influx models included with the mass and energy balances are adopted from the petroleum engineering literature. The match to production data from Svartsengi is improved when influx was included. The Schilthuis steady-state influx gives a satisfactory match. The finite aquifer method of Fetkovitch, and the unsteady state method of Hurst gave reasonable answers, but not as good. The best match is obtained using Hurst simplified solution when lambda = 1.3 x 10{sup -4} m{sup -1}. From the match the cross-sectional area of the aquifer was calculated as 3.6 km{sup 2}. The drawdown was predicted using the Hurst simplified method, and compared with predicted drawdown from a boiling model and an empirical log-log model. A large difference between the models was obtained. The predicted drawdown using the Hurst simplified method falls between the other two. Injection has been considered by defining the net rate as being the production rate minus the injection rate. No thermal of transient effects were taken into account. Prediction using three different net rates shows that the pressure can be maintained using the Hurst simplified method if there is significant fluid reinjection. 32 refs., 44 figs., 2 tabs.

  11. Renal cortical pyruvate depletion during AKI.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Becker, Kirsten

    2014-05-01

    Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15-60 minutes; 0-18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.

  12. Barium depletion in hollow cathode emitters

    SciTech Connect

    Polk, James E. Mikellides, Ioannis G.; Katz, Ira; Capece, Angela M.

    2016-01-14

    Dispenser hollow cathodes rely on a consumable supply of Ba released by BaO-CaO-Al{sub 2}O{sub 3} source material in the pores of a tungsten matrix to maintain a low work function surface. The examination of cathode emitters from long duration tests shows deposits of tungsten at the downstream end that appear to block the flow of Ba from the interior. In addition, a numerical model of Ba transport in the cathode plasma indicates that the Ba partial pressure in the insert may exceed the equilibrium vapor pressure of the dominant Ba-producing reaction, and it was postulated previously that this would suppress Ba loss in the upstream part of the emitter. New measurements of the Ba depletion depth from a cathode insert operated for 8200 h reveal that Ba loss is confined to a narrow region near the downstream end, confirming this hypothesis. The Ba transport model was modified to predict the depletion depth with time. A comparison of the calculated and measured depletion depths gives excellent qualitative agreement, and quantitative agreement was obtained assuming an insert temperature 70 °C lower than measured beginning-of-life values.

  13. Pumping test evaluation of stream depletion parameters.

    PubMed

    Lough, Hilary K; Hunt, Bruce

    2006-01-01

    Descriptions are given of a pumping test and a corresponding analysis that permit calculation of all five hydrogeological parameters appearing in the Hunt (2003) solution for stream depletion caused by ground water abstraction from a well beside a stream. This solution assumes that flow in the pumped aquifer is horizontal, flow in the overlying aquitard or system of aquitards is vertical, and the free surface in the top aquitard is allowed to draw down. The definition of an aquitard in this paper is any layer with a vertical hydraulic conductivity much lower than the horizontal hydraulic conductivity of the pumped aquifer. These "aquitards" may be reasonably permeable layers but are distinguished from the pumped aquifer by their hydraulic conductivity contrast. The pumping test requires a complete set of drawdown measurements from at least one observation well. This well must be deep enough to penetrate the pumped aquifer, and pumping must continue for a sufficient time to ensure that depleted streamflow becomes a significant portion of the well abstraction rate. Furthermore, two of the five parameters characterize an aquitard that overlies the pumped aquifer, and values for these parameters are seen to be dependent upon the initial water table elevation in the aquitard. The field test analyzed herein used a total of eight observation wells screened in the pumped aquifer, and measurements from these wells gave eight sets of parameters that are used in a sensitivity analysis to determine the relative importance of each parameter in the stream depletion calculations.

  14. Chronic lymphocytic leukemia: molecular genetics and animal models.

    PubMed

    Pekarsky, Y; Calin, G A; Aqeilan, R

    2005-01-01

    Chronic lymphocytic leukemia accounts for almost 30% of all adult leukemia cases in the United States and Western Europe. Although several common genomic abnormalities in CLL have been identified, mutational and functional analysis of corresponding genes so far have not proved their involvement in CLL. Our latest studies demonstrated functional involvement of Tcl1 oncoprotein and microRNA genes in the pathogenesis of CLL. Deregulated expression of Tcl1 in transgenic mice resulted in CLL. These CLL tumors showed abnormalities in expression of murine microRNA genes mmu-mir-15a and mmu-mir-16-1. Interestingly, human homologs of these genes, mir-15a and mir-16-1, located at the chromosome 13q14 are also deleted in human CLL samples. In this review we summarize and discuss these new developments. These recently emerged insights into the molecular mechanisms of CLL will allow for the development of new approaches to treat this disease.

  15. Novel Therapies for Chronic Lymphocytic Leukemia: A Canadian Perspective.

    PubMed

    Owen, Carolyn; Assouline, Sarit; Kuruvilla, John; Uchida, Cassandra; Bellingham, Catherine; Sehn, Laurie

    2015-11-01

    Chronic lymphocytic leukemia (CLL) is the most common adult lymphoproliferative disorder in Western countries. The current standard of care for CLL is chemoimmunotherapy, typically with fludarabine, cyclophosphamide, and rituximab (FCR). However, most patients with CLL are elderly with comorbidities and are unable to tolerate FCR. In order to choose the best treatment for each individual patient, physicians must balance efficacy with toxicity. In addition, most currently available treatments are ineffective in CLL patients with loss of TP53. Two groups of novel therapeutic agents-anti-CD20 monoclonal antibodies and small molecule inhibitors-are attempting to address these issues, and 5 of these agents have progressed to phase 3 trials: obinutuzumab, idelalisib, ibrutinib, venetoclax (ABT-199), and duvelisib (IPI-145). We present the current evidence for these novel agents in the treatment of CLL, along with the perspectives of 4 Canadian oncology experts.

  16. Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  17. Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation.

    PubMed

    Ciceri, F; Bonini, C; Gallo-Stampino, C; Bordignon, C

    2005-01-01

    In allogeneic hematopoietic cell transplantation (allo-HCT), donor lymphocytes play a central therapeutic role in both GvL and immune reconstitution. However, the full exploitation of these therapeutic properties is limited by the occurrence of GvHD. Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. The genetic engineering of donor lymphocytes with the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene confers the ability to modulate GvHD by invivo ganciclovir-induced elimination of the transduced cells. The suicide-gene strategy has applications in both donor lymphocyte infusion (DLI) for disease relapse and in add-back infusions after T-cell depleted allo-HCT. TK cell DLI resulted in anti-tumor activity in a relevant proportion of treated patients. Haplo-identical stem cell transplantation (haplo-HCT) is a promising therapeutic option for patients with high risk hematologic malignancies lacking an HLA-matched donor. However, the profound T-cell depletion required to overcome the risk of lethal GvHD has been associated with a marked delayed T-cell recovery with a prolonged risk of post-transplant viral, fungal and other opportunistic infections. TK cell add-backs efficiently promote early immune reconstitution after haplo-HCT and prevent disease relapse, providing a unique tool for the control of GvHD. The genetic manipulation of donor lymphocytes with a suicide gene is a promising strategy to increase feasibility and safety of allo-HCT.

  18. Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

    PubMed Central

    Kwack, Kyu Hwan

    2017-01-01

    We have examined the effect of progranulin (PGRN) on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-β. PMID:28194047

  19. Characterization of the atypical lymphocytes in African swine fever

    PubMed Central

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

    2016-01-01

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

  20. Insomnia Caused by Serotonin Depletion is Due to Hypothermia

    PubMed Central

    Murray, Nicholas M.; Buchanan, Gordon F.; Richerson, George B.

    2015-01-01

    Study Objective: Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation. Design: Adult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20°C (normal room temperature) or at 33°C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4°C for 4 h to characterize their ability to thermoregulate. Measurements and Results: PCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20°C spent significantly more time awake than controls. However, core body temperature decreased from 36.5°C to 35.1°C. When housed at 33°C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4°C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature. Conclusions: These results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion. Citation: Murray NM, Buchanan GF, Richerson GB. Insomnia caused by serotonin depletion is due to hypothermia. SLEEP 2015;38(12):1985–1993. PMID:26194567

  1. Janus kinase 3 is expressed in erythrocytes, phosphorylated upon energy depletion and involved in the regulation of suicidal erythrocyte death.

    PubMed

    Bhavsar, Shefalee K; Gu, Shuchen; Bobbala, Diwakar; Lang, Florian

    2011-01-01

    Janus kinase 3, a tyrosine kinase expressed in haematopoetic tissues, plays a decisive role in T-lymphocyte survival. JAK3 deficiency leads to (Severe) Combined Immunodeficiency (SCID) resulting from enhanced lymphocyte apoptosis. JAK3 is activated by phosphorylation. Nothing is known about expression of JAK3 in erythrocytes, which may undergo apoptosis-like cell death (eryptosis) characterized by cell membrane scrambling with phosphatidylserine exposure and cell shrinkage. Triggers of eryptosis include energy depletion. The present study utilized immunohistochemistry and confocal microscopy to test for JAK3 expression and phosphorylation, and FACS analysis to determine phosphatidylserine exposure (annexin binding) and cell volume (forward scatter). As a result, JAK3 was expressed in erythrocytes and phosphorylated following 24h and 48h glucose depletion. Forward scatter was slightly but significantly smaller in erythrocytes from JAK3-deficient mice (jak3(-/-)) than in erythrocytes from wild type mice (jak3(+/+)). Annexin V binding was similarly low in both genotypes. The JAK3 inhibitors WHI-P131/JANEX-1 (4-(4'-Hydroxyphenyl)amino-6,7-dimethoxyquinazoline, 156μM) and WHI-P154 (4-[(3'-Bromo-4'-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 11.2μM) did not significantly modify annexin V binding or forward scatter. Glucose depletion increased annexin V binding, an effect significantly blunted in jak3(-/-) erythrocytes and in the presence of the JAK3 inhibitors. The observations disclose a completely novel role of Janus kinase 3, i.e. the triggering of cell membrane scrambling in energy depleted erythrocytes.

  2. Lymphocyte suppressor activity in atopic eczema

    PubMed Central

    Ogden, B. E.; Krueger, G. G.; Hill, H. R.

    1979-01-01

    Previous studies have shown that patients with atopic eczema have depressed cell-mediated immunity. Whether this defect can be attributed to abnormal suppressor cell activity or to the presence of mediators of the allergic response has not been studied before. Lymphocyte transformation was found to be enhanced in patients with mild eczema and markedly depressed in patients with severe eczema, when compared with normal controls. Pre-incubation of cultures for 48 hr without mitogen prior to transformation studies restored normal lymphocyte thymidine uptake in cells from severe atopics, suggesting a labile suppressor cell population, or a labile suppressor substance. Since mononuclear cell supernatants from patients with severe eczema failed to suppress lymphocyte transformation more than supernatants from normals, it is unlikely that the depressed lymphocyte function seen in severe eczema is due to an abnormal suppressor cell population. The possibility that mediators of the allergic response may be acting as a labile suppressor substance was evaluated by adding various concentrations of histamine, cyclic-AMP, or prostaglandin E1 to lymphocytes undergoing mitogenesis. Histamine enhanced thymidine incorporation at low concentrations and depressed uptake at high concentrations; cyclic-AMP and prostaglandin E1 have similar effects on transformation. It is possible that the enhancement of transformation seen in mild eczema and the depression of this response in severe eczema may be related to the concentrations or degree of allergic mediator release. PMID:219977

  3. B lymphocytes: how they develop and function.

    PubMed

    LeBien, Tucker W; Tedder, Thomas F

    2008-09-01

    The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries.

  4. B lymphocytes: how they develop and function

    PubMed Central

    2008-01-01

    The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries. PMID:18725575

  5. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

    PubMed Central

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent. PMID:26430172

  6. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study.

    PubMed

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-12-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.

  7. T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.

    PubMed

    Vago, Luca; Oliveira, Giacomo; Bondanza, Attilio; Noviello, Maddalena; Soldati, Corrado; Ghio, Domenico; Brigida, Immacolata; Greco, Raffaella; Lupo Stanghellini, Maria Teresa; Peccatori, Jacopo; Fracchia, Sergio; Del Fiacco, Matteo; Traversari, Catia; Aiuti, Alessandro; Del Maschio, Alessandro; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara

    2012-08-30

    The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

  8. Deoxynivalenol induced oxidative stress and genotoxicity in human peripheral blood lymphocytes.

    PubMed

    Yang, Wei; Yu, Miao; Fu, Juan; Bao, Wei; Wang, Di; Hao, Liping; Yao, Ping; Nüssler, Andreas K; Yan, Hong; Liu, Liegang

    2014-02-01

    Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study consists in using diverse cellular and molecular assays to evaluate cytotoxicity, genotoxicity as well as oxidative damage and to investigate their mechanisms in human peripheral blood lymphocytes. The human lymphocytes were cultured in eight different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6, 12 and 24 h. DON was able to decrease cell viability and cause damage to the membrane, the chromosomes or the DNA at all times of culture. It was also able to induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24 h. The results of the RT-PCR and the Western Blot indicated that DON is able to enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human lymphocytes. This mechanism is probably related to depletion of antioxidase and oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting the ability of DNA repair.

  9. Weft, warp, and weave: the intricate tapestry of calcium channels regulating T lymphocyte function.

    PubMed

    Omilusik, Kyla D; Nohara, Lilian L; Stanwood, Shawna; Jefferies, Wilfred A

    2013-01-01

    Calcium (Ca(2+)) is a universal second messenger important for T lymphocyte homeostasis, activation, proliferation, differentiation, and apoptosis. The events surrounding Ca(2+) mobilization in lymphocytes are tightly regulated and involve the coordination of diverse ion channels, membrane receptors, and signaling molecules. A mechanism termed store-operated Ca(2+) entry (SOCE), causes depletion of endoplasmic reticulum (ER) Ca(2+) stores following T cell receptor (TCR) engagement and triggers a sustained influx of extracellular Ca(2+) through Ca(2+) release-activated Ca(2+) (CRAC) channels in the plasma membrane. The ER Ca(2+) sensing molecule, stromal interaction molecule 1 (STIM1), and a pore-forming plasma membrane protein, ORAI1, have been identified as important mediators of SOCE. Here, we review the role of several additional families of Ca(2+) channels expressed on the plasma membrane of T cells that likely contribute to Ca(2+) influx following TCR engagement, particularly highlighting an important role for voltage-dependent Ca(2+) channels (CaV) in T lymphocyte biology.

  10. Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes.

    PubMed

    Ugel, Stefano; Scarselli, Elisa; Iezzi, Manuela; Mennuni, Carmela; Pannellini, Tania; Calvaruso, Francesco; Cipriani, Barbara; De Palma, Raffaele; Ricci-Vitiani, Lucia; Peranzoni, Elisa; Musiani, Piero; Zanovello, Paola; Bronte, Vincenzo

    2010-02-18

    Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy.

  11. L-arginine metabolism in myeloid cells controls T-lymphocyte functions.

    PubMed

    Bronte, Vincenzo; Serafini, Paolo; Mazzoni, Alessandra; Segal, David M; Zanovello, Paola

    2003-06-01

    Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.

  12. Synthesis and toxicity assessment of 3-oxobutanamides against human lymphocytes and isolated mitochondria.

    PubMed

    Razzaghi-Asl, Nima; Seydi, Enaytollah; Alikhani, Radin; Rezvani, Saba; Miri, Ramin; Salimi, Ahmad

    2017-03-07

    To reduce costly late-phase compound scrubbing, there has been an increased focus on assessing compounds within in vitro assays that predict properties of human safety liabilities, before preclinical in vivo studies. The aim of our study was to answer the questions that whether the toxicity risk of a series of 3-oxobutanamide derivatives could be predicted by using of human lymphocytes and their isolated mitochondria. Using biochemical and flow cytometry assessments, we demonstrated that exposure of lymphocytes and isolated mitochondria to five 3-oxobutanamide derivatives (1-5) did not exhibit remarkable toxicity at low concentrations (50-500μM) but toxicity could be observed at high concentrations (1000 and 2000μM), particularly for N-(5-(4-bromophenyl)-3-isoxazolyl)-3-oxobutanamide (4) and N-(2-benzothiazolyl)-3-oxo butanamide (5). Compounds 4, 5 and partly N-(5-methyl-3-isoxazol yl)-3-oxo butanamide (1) also showed a marked cellular and mitochondrial toxicity while compound 5 displayed superior toxicity. Compound 5 induced cytotoxicity on human blood lymphocytes which was associated with the generation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation and depletion of glutathione. Our results suggested that among assessed compounds, increased toxicity of compound 5 compared to other compounds could be likely attributed to the presence of bromine substituent in 5. Finally our findings proposed that using of antioxidants and mitochondrial/lysosomal protective agents could be beneficial in decreasing the toxicity of 5.

  13. Belatacept and Sirolimus Prolong Nonhuman Primate Renal Allograft Survival without a Requirement for Memory T Cell Depletion

    PubMed Central

    Lo, Denise J; Anderson, Douglas J; Weaver, Timothy A; Leopardi, Frank; Song, Mingqing; Farris, Alton B; Strobert, Elizabeth A; Jenkins, Joe; Turgeon, Nicole A; Mehta, Aneesh K; Larsen, Christian P; Kirk, Allan D

    2012-01-01

    Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal transplantation. We sought to develop a clinically translatable, non-lymphocyte depleting, belatacept-based regimen that could obviate the need for both CNIs and steroids. Thus, based on murine data showing synergy between costimulation blockade and mTOR inhibition, we studied rhesus monkeys undergoing MHC-mismatched renal allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on costimulation blockade-resistant rejection, some animals also received CD2 blockade with alefacept (LFA3-Ig). Belatacept and sirolimus therapy successfully prevented rejection in all animals. Tolerance was not induced, as animals rejected after withdrawal of therapy. The regimen did not deplete T cells. Alefecept did not add a survival benefit to the optimized belatacept and sirolimus regimen, despite causing an intended depletion of memory T cells, and caused a marked reduction in regulatory T cells. Furthermore, alefacept treated animals had a significantly increased incidence of CMV reactivation, suggesting that this combination overly compromised protective immunity. These data support belatacept and sirolimus as a clinically translatable, non-depleting, CNI-free, steroid-sparing immunomodulatory regimen that promotes sustained rejection-free allograft survival after renal transplantation. PMID:23311611

  14. 26 CFR 1.613-1 - Percentage depletion; general rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion; general rule. (a) In general. In the case of a taxpayer computing the deduction for depletion under section 611... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Percentage depletion; general rule....

  15. 26 CFR 1.613-1 - Percentage depletion; general rule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion; general rule. (a) In general. In the case of a taxpayer computing the deduction for depletion under section 611... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Percentage depletion; general rule....

  16. 26 CFR 1.613-1 - Percentage depletion; general rule.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion; general rule. (a) In general. In the case of a taxpayer computing the deduction for depletion under section 611... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Percentage depletion; general rule....

  17. 26 CFR 1.613-1 - Percentage depletion; general rule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion; general rule. (a) In general. In the case of a taxpayer computing the deduction for depletion under section 611... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Percentage depletion; general rule....

  18. 26 CFR 52.4682-1 - Ozone-depleting chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section...

  19. 26 CFR 52.4682-1 - Ozone-depleting chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section...

  20. 26 CFR 52.4682-1 - Ozone-depleting chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section...

  1. 26 CFR 52.4682-1 - Ozone-depleting chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section...

  2. Children's Models of the Ozone Layer and Ozone Depletion.

    ERIC Educational Resources Information Center

    Christidou, Vasilia; Koulaidis, Vasilis

    1996-01-01

    The views of 40 primary students on ozone and its depletion were recorded through individual, semi-structured interviews. The data analysis resulted in the formation of a limited number of models concerning the distribution and role of ozone in the atmosphere, the depletion process, and the consequences of ozone depletion. Identifies five target…

  3. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent...

  4. T cell immunity using transgenic B lymphocytes

    NASA Astrophysics Data System (ADS)

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

    2004-03-01

    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.

  5. Nodular lymphocyte-predominant Hodgkin lymphoma.

    PubMed

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

    2016-07-01

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

  6. Natural effector T lymphocytes in normal mice.

    PubMed Central

    Pereira, P; Larsson, E L; Forni, L; Bandeira, A; Coutinho, A

    1985-01-01

    The "natural" T-cell activity in normal unimmunized mice was studied. By double-parameter fluorescence-activated cell sorter analysis, it was found that 5-10% of all splenic Lyt-2+ and L3T4+ lymphocytes are large, of which more than half are in mitotic cycle. In contrast with small resting cells of the same phenotype, activated (large) T cells isolated from normal mice are functional effector cells: L3T4+ large cells induce normal B lymphocytes into proliferation and antibody secretion, while large Lyt-2+ cells efficiently suppress B-lymphocyte responses. No effector cell cytolytic activity could be detected among naturally activated T cells. The significance of these findings for the internal activity in the normal immune system is discussed. PMID:2933744

  7. A modern depleted uranium manufacturing facility

    SciTech Connect

    Zagula, T.A.

    1995-07-01

    The Specific Manufacturing Capabilities (SMC) Project located at the Idaho National Engineering Laboratory (INEL) and operated by Lockheed Martin Idaho Technologies Co. (LMIT) for the Department of Energy (DOE) manufactures depleted uranium for use in the U.S. Army MIA2 Abrams Heavy Tank Armor Program. Since 1986, SMC has fabricated more than 12 million pounds of depleted uranium (DU) products in a multitude of shapes and sizes with varying metallurgical properties while maintaining security, environmental, health and safety requirements. During initial facility design in the early 1980`s, emphasis on employee safety, radiation control and environmental consciousness was gaining momentum throughout the DOE complex. This fact coupled with security and production requirements forced design efforts to focus on incorporating automation, local containment and computerized material accountability at all work stations. The result was a fully automated production facility engineered to manufacture DU armor packages with virtually no human contact while maintaining security, traceability and quality requirements. This hands off approach to handling depleted uranium resulted in minimal radiation exposures and employee injuries. Construction of the manufacturing facility was complete in early 1986 with the first armor package certified in October 1986. Rolling facility construction was completed in 1987 with the first certified plate produced in the fall of 1988. Since 1988 the rolling and manufacturing facilities have delivered more than 2600 armor packages on schedule with 100% final product quality acceptance. During this period there was an annual average of only 2.2 lost time incidents and a single individual maximum radiation exposure of 150 mrem. SMC is an example of designing and operating a facility that meets regulatory requirements with respect to national security, radiation control and personnel safety while achieving production schedules and product quality.

  8. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes.

    PubMed

    Zaynagetdinov, R; Stathopoulos, G T; Sherrill, T P; Cheng, D-S; McLoed, A G; Ausborn, J A; Polosukhin, V V; Connelly, L; Zhou, W; Fingleton, B; Peebles, R S; Prince, L S; Yull, F E; Blackwell, T S

    2012-06-28

    The mechanisms by which chronic inflammatory lung diseases, particularly chronic obstructive pulmonary disease, confer enhanced risk for lung cancer are not well-defined. To investigate whether nuclear factor (NF)-κB, a key mediator of immune and inflammatory responses, provides an interface between persistent lung inflammation and carcinogenesis, we utilized tetracycline-inducible transgenic mice expressing constitutively active IκB kinase β in airway epithelium (IKTA (IKKβ trans-activated) mice). Intraperitoneal injection of ethyl carbamate (urethane), or 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) was used to induce lung tumorigenesis. Doxycycline-treated IKTA mice developed chronic airway inflammation and markedly increased numbers of lung tumors in response to urethane, even when transgene expression (and therefore epithelial NF-κB activation) was begun after exposure to carcinogen. Studies using a separate tumor initiator/promoter model (MCA+BHT) indicated that NF-κB functions as an independent tumor promoter. Enhanced tumor formation in IKTA mice was preceded by increased proliferation and reduced apoptosis of alveolar epithelium, resulting in increased formation of premalignant lesions. Investigation of inflammatory cells in lungs of IKTA mice revealed a substantial increase in macrophages and lymphocytes, including functional CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Importantly, Treg depletion using repetitive injections of anti-CD25 antibodies limited excessive tumor formation in IKTA mice. At 6 weeks following urethane injection, antibody-mediated Treg depletion in IKTA mice reduced the number of premalignant lesions in the lungs in association with an increase in CD8 lymphocytes. Thus, persistent NF-κB signaling in airway epithelium facilitates carcinogenesis by sculpting the immune/inflammatory environment in the lungs.

  9. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes

    PubMed Central

    Tamás, Peter; Hawley, Simon A.; Clarke, Rosemary G.; Mustard, Kirsty J.; Green, Kevin; Hardie, D. Grahame; Cantrell, Doreen A.

    2006-01-01

    The adenosine monophosphate (AMP)–activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca2+ with Ca2+ ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca2+ stimulation of AMPK required the activity of Ca2+–calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it. PMID:16818670

  10. Correlation between cosmic rays and ozone depletion.

    PubMed

    Lu, Q-B

    2009-03-20

    This Letter reports reliable satellite data in the period of 1980-2007 covering two full 11-yr cosmic ray (CR) cycles, clearly showing the correlation between CRs and ozone depletion, especially the polar ozone loss (hole) over Antarctica. The results provide strong evidence of the physical mechanism that the CR-driven electron-induced reaction of halogenated molecules plays the dominant role in causing the ozone hole. Moreover, this mechanism predicts one of the severest ozone losses in 2008-2009 and probably another large hole around 2019-2020, according to the 11-yr CR cycle.

  11. Depletion of the Outer Asteroid Belt

    NASA Technical Reports Server (NTRS)

    Liou, Jer-Chyi; Malhotra, Renu

    1997-01-01

    During the early history of the solar system, it is likely that the outer planets changed their distance from the sun, and hence, their influence on the asteroid belt evolved with time. The gravitational influence of Jupiter and Saturn on the orbital evolution of asteroids in the outer asteroid belt was calculated. The results show that the sweeping of mean motion resonances associated with planetary migration efficiently destabilizes orbits in the outer asteroid belt on a time scale of 10 million years. This mechanism provides an explanation for the observed depletion of asteroids in that region.

  12. Ozone depletion: implications for the veterinarian.

    PubMed

    Kopecky, K E

    1978-09-15

    Man has inadvertently modified the stratosphere. There is a good possibility that the ozone layer is being depleted by the use of jet aircraft (SST), chlorofluoromethane propellants, and nitrogen fertilizers. Under unpolluted conditions, the production of ozone equals its destruction. By man's intervention, however, the destruction may exceed the production. The potential outcome is increased intensity of solar ultraviolet (280-400 nm) radiation and penetration to the earth's surface of previously absorbed wavelengths below about 280 nm. The increased ultraviolet radiation would increase the likelihood of skin cancer in man and ocular squamous cell carcinoma in cattle. The climate also might be modified, possibly in an undesirable way.

  13. Capstone Depleted Uranium Aerosols: Generation and Characterization

    SciTech Connect

    Parkhurst, MaryAnn; Szrom, Fran; Guilmette, Ray; Holmes, Tom; Cheng, Yung-Sung; Kenoyer, Judson L.; Collins, John W.; Sanderson, T. Ellory; Fliszar, Richard W.; Gold, Kenneth; Beckman, John C.; Long, Julie

    2004-10-19

    In a study designed to provide an improved scientific basis for assessing possible health effects from inhaling depleted uranium (DU) aerosols, a series of DU penetrators was fired at an Abrams tank and a Bradley fighting vehicle. A robust sampling system was designed to collect aerosols in this difficult environment and continuously monitor the sampler flow rates. Aerosols collected were analyzed for uranium concentration and particle size distribution as a function of time. They were also analyzed for uranium oxide phases, particle morphology, and dissolution in vitro. The resulting data provide input useful in human health risk assessments.

  14. Commercialisation of full depletion scientific CCDs

    NASA Astrophysics Data System (ADS)

    Jorden, Paul; Ball, Kevin; Bell, Ray; Burt, David; Guyatt, Neil; Hadfield, Kevin; Jerram, Paul; Pool, Peter; Pike, Andrew; Holland, Andrew; Murray, Neil

    2006-06-01

    Following successful manufacture of small-format trial devices we have now designed and manufactured large-format scientific CCDs in high resistivity silicon ('high-rho'). These devices are intended for 'full depletion' operation as backside illuminated sensors for very high red wavelength sensitivity and X-ray imaging spectroscopy at extended energies. Devices of 2k*512 and 2k*4k format, with both single and dual stage output circuits have been manufactured and tested. Design considerations, test results, and commercial manufacturing considerations will be addressed.

  15. Scientific assessment of ozone depletion: 1991

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Over the past few years, there have been highly significant advances in the understanding of the impact of human activities on the Earth's stratospheric ozone layer and the influence of changes in chemical composition of the radiative balance of the climate system. Specifically, since the last international scientific review (1989), there have been five major advances: (1) global ozone decreases; (2) polar ozone; (3) ozone and industrial halocarbons; (4) ozone and climate relations; and (5) ozone depletion potentials (ODP's) and global warming potentials (GWP's). These topics and others are discussed.

  16. Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

    PubMed Central

    Laurence, J; Mitra, D; Steiner, M; Lynch, D H; Siegal, F P; Staiano-Coico, L

    1996-01-01

    Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. PMID:8609222

  17. A receptor for 'self' on lymphocytes.

    PubMed Central

    Kolb, H

    1977-01-01

    A large population of lymphocytes is able to form rosettes with syngeneic, allogeneic or closely related xenogeneic erythrocytes. Similar results were found with spleen cells from mice, rats and rabbits. The highest numbers were found in mice where up to 30% of lymphocytes bound autologous erythrocytes. Rosette formation is probably due to stereospecific cell surface receptors since erythrocytes of distant xenogeneic origin were not recognized. Rosette forming cells do not seem to be restricted to the B-cell or T-cell compartment since mouse thymus cells as well as spleen cells from congenitally athymic (nude) mice bound erythrocytes to a similar degree. PMID:73501

  18. [Amalgam fillings and T-lymphocyte changes].

    PubMed

    Giuliani, M; Rumi, C; Marciani, F; Boari, A; Rumi, G; Di Felice, R

    1990-07-01

    Dental amalgam and nickel alloys have been considered quite safe. Previous authors reported the effect of dental amalgam and nickel alloys on human T-lymphocytes modifications after amalgam dental fillings, into dose-dependence of any modifications and into possible temporary. Eight patients were subjected to dental care with amalgam dental fillings. Drawings of blood were executed at start, fifteen days after late fillings and two months later. The results about modifications of T-lymphocytes were not univocal. We believe, at now, that temporary modifications of the immunity seem to be related to a cytotoxic mechanism.

  19. Simulations and observations of plasma depletion, ion composition, and airglow emissions in two auroral ionospheric depletion experiments

    NASA Technical Reports Server (NTRS)

    Yau, A. W.; Whalen, B. A.; Harris, F. R.; Gattinger, R. L.; Pongratz, M. B.

    1985-01-01

    Observations of plasma depletion, ion composition modification, and airglow emissions in the Waterhole experiments are presented. The detailed ion chemistry and airglow emission processes related to the ionospheric hole formation in the experiment are examined, and observations are compared with computer simulation results. The latter indicate that the overall depletion rates in different parts of the depletion region are governed by different parameters.

  20. Elevated expression of pleiotrophin in lymphocytic leukemia CD19+ B cells.

    PubMed

    Du, Chun-Xian; Wang, Lan; Li, Yan; Xiao, Wei; Guo, Qin-Lian; Chen, Fei; Tan, Xin-Ti

    2014-10-01

    Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia.

  1. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia

    PubMed Central

    1982-01-01

    An infrequent (2-3%) B lymphocyte subpopulation was found in the normal human tonsil and lymph nodes that shows the phenotypic characteristics of B-chronic lymphocytic leukemia (B-CLL) (rosette formation with mouse erythrocytes, weak expression of membrane Ig, staining for HLA-DR, and OKT1 or Leu-1 detecting a T cell-associated p65 antigen). Preliminary evidence suggests that at least a subpopulation of these cells is found, in small proportions, within the germinal centers. These cells were not observed in the human bone marrow. B-CLL may involve this peripheral B lymphocyte subset. PMID:6977012

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

    PubMed Central

    DOI, Takuya; TOMONARI, Yuki; KAWASAKO, Kazufumi; YAMADA, Naoaki; TSUCHITANI, Minoru

    2016-01-01

    Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown. PMID:27885217

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

    PubMed

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

    2017-02-04

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

  4. Ego depletion results in an increase in spontaneous false memories.

    PubMed

    Otgaar, Henry; Alberts, Hugo; Cuppens, Lesly

    2012-12-01

    The primary aim of the current study was to examine whether depleted cognitive resources might have ramifications for the formation of neutral and negative spontaneous false memories. To examine this, participants received neutral and negative Deese/Roediger-McDermott false memory wordlists. Also, for half of the participants, cognitive resources were depleted by use of an ego depletion manipulation (solving difficult calculations while being interfered with auditory noise). Our chief finding was that depleted cognitive resources made participants more vulnerable for the production of false memories. Our results shed light on how depleted cognitive resources affect neutral and negative correct and errant memories.

  5. Decline and depletion rates of oil production: a comprehensive investigation.

    PubMed

    Höök, Mikael; Davidsson, Simon; Johansson, Sheshti; Tang, Xu

    2014-01-13

    Two of the most fundamental concepts in the current debate about future oil supply are oilfield decline rates and depletion rates. These concepts are related, but not identical. This paper clarifies the definitions of these concepts, summarizes the underlying theory and empirically estimates decline and depletion rates for different categories of oilfield. A database of 880 post-peak fields is analysed to determine typical depletion levels, depletion rates and decline rates. This demonstrates that the size of oilfields has a significant influence on decline and depletion rates, with generally high values for small fields and comparatively low values for larger fields. These empirical findings have important implications for oil supply forecasting.

  6. Imaging neurotransmitter uptake and depletion in astrocytes

    SciTech Connect

    Tan, W. |; Haydon, P.G.; Yeung, E.S.

    1997-08-01

    An ultraviolet (UV) laser-based optical microscope and charge-coupled device (CCD) detection system was used to obtain chemical images of biological cells. Subcellular structures can be easily seen in both optical and fluorescence images. Laser-induced native fluorescence detection provides high sensitivity and low limits of detection, and it does not require coupling to fluorescent dyes. We were able to quantitatively monitor serotonin that has been taken up into and released from individual astrocytes on the basis of its native fluorescence. Different regions of the cells took up different amounts of serotonin with a variety of uptake kinetics. Similarly, we observed different serotonin depletion dynamics in different astrocyte regions. There were also some astrocyte areas where no serotonin uptake or depletion was observed. Potential applications include the mapping of other biogenic species in cells as well as the ability to image their release from specific regions of cells in response to external stimuli. {copyright} {ital 1997} {ital Society for Applied Spectroscopy}

  7. Halocarbon ozone depletion and global warming potentials

    NASA Technical Reports Server (NTRS)

    Cox, Richard A.; Wuebbles, D.; Atkinson, R.; Connell, Peter S.; Dorn, H. P.; Derudder, A.; Derwent, Richard G.; Fehsenfeld, F. C.; Fisher, D.; Isaksen, Ivar S. A.

    1990-01-01

    Concern over the global environmental consequences of fully halogenated chlorofluorocarbons (CFCs) has created a need to determine the potential impacts of other halogenated organic compounds on stratospheric ozone and climate. The CFCs, which do not contain an H atom, are not oxidized or photolyzed in the troposphere. These compounds are transported into the stratosphere where they decompose and can lead to chlorine catalyzed ozone depletion. The hydrochlorofluorocarbons (HCFCs or HFCs), in particular those proposed as substitutes for CFCs, contain at least one hydrogen atom in the molecule, which confers on these compounds a much greater sensitivity toward oxidation by hydroxyl radicals in the troposphere, resulting in much shorter atmospheric lifetimes than CFCs, and consequently lower potential for depleting ozone. The available information is reviewed which relates to the lifetime of these compounds (HCFCs and HFCs) in the troposphere, and up-to-date assessments are reported of the potential relative effects of CFCs, HCFCs, HFCs, and halons on stratospheric ozone and global climate (through 'greenhouse' global warming).

  8. Stratospheric ozone depletion and animal health.

    PubMed

    Mayer, S J

    1992-08-08

    There is an increasing concern over ozone depletion and its effects on the environment and human health. However, the increase in ultraviolet-B radiation (UV-B) that would result from significant losses of ozone is also potentially harmful to animals. Any increase in disease in domestic species would not only have serious animal welfare implications but may also be economically important. The diseases which are likely to increase if ozone depletion continues include the squamous cell carcinomas of the exposed, non-pigmented areas of cats, cattle, sheep and horses. Uberreiter's syndrome in dogs is also associated with exposure to UV-B and may be expected to increase, as may the severity of conditions such as infectious keratoconjunctivitis (New Forest eye) in cattle. Aquaculture systems in which fish often have little or no protection by shading may also be at risk. Cataracts and skin lesions have been associated with the exposure of farmed fish to ultraviolet radiation and have resulted in significant losses.

  9. Signaling via the CD2 receptor enhances HTLV-1 replication in T lymphocytes.

    PubMed

    Guyot, D J; Newbound, G C; Lairmore, M D

    1997-07-21

    Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of adult T cell leukemia/lymphoma and several chronic progressive immune-mediated diseases. Approximately 1-4% of infected individuals develop disease, generally decades following infection. Increased proviral transcription, mediated by the viral 40-kDa trans-activating protein, Tax, has been implicated in the pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains sequences responsive to cyclic AMP and protein kinase C, we hypothesized that lymphocyte activation signals initiated through the TCR/CD3 complex or CD2 receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate that mAbs directed against the CD2, but not the CD3 receptor increase viral p24 capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an immortalized HTLV-1 cell line. Consistent with transcriptional regulation, reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene construct under control of the HTLV-1 promoter. These data suggest a possible physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte activation may promote viral transcription in infected lymphocytes.

  10. Response of lymphocytes to a mitogenic stimulus during spaceflight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1989-01-01

    Several studies were performed that demonstrate that immunological activities of lymphocytes can be affected by spaceflight or by models that attempt to simulate some aspects of weightlessness. Included among these are the responses of lymphocytes to external stimuli such as mitogens and viruses. When cultures of lymphocytes were flown in space, the ability of the lymphocytes to respond to mitogens was inhibited. Similar results were obtained when lymphocytes from astronauts or animals just returned from space were placed into culture immediately upon return to earth, and when models of hypogravity were used. Lymphocytes placed in culture during spaceflights produced enhanced levels of interferon compared to control cultures. When cultures of lymphocytes were prepared for cosmonauts or rodents immediately upon return to earth, interferon production was inhibited. These results suggest that space flight can have profound effects on lymphocyte function, and that effects on isolated cells may be different from that on cells in the whole organism.

  11. Analysis of leukocyte binding to depletion filters: role of passive binding, interaction with platelets, and plasma components.

    PubMed

    Henschler, R; Rüster, B; Steimle, A; Hansmann, H L; Walker, W; Montag, T; Seifried, E

    2005-08-01

    Since limited knowledge exists on the mechanisms which regulate cell binding to leukocyte removal filter surfaces, we investigated the binding patterns of leukocytes to individual layers of leukocyte depletion filters. After passage of 1 unit of whole blood, blotting of isolated filter layers on glass slides or elution of cells from filter layers revealed that most leukocytes were located within the first 10 of a total of 28 filter layers, peaking at layers 6 to 8, with granulocytes binding on average to earlier filter layers than lymphocytes. Leukocytes preincubated with inhibitors of actin activation showed unchanged distribution between filter layers, suggesting that cytoskeletal activation does not significantly contribute to their binding. When leukocytes were directly incubated with single filter layers, binding of up to 30% of input cells was recorded in the absence of Ca(2+). Immunohistological analyses showed colocalization of platelets and leukocytes, with co-clustering of platelets and leukocytes. Monocytes and to some degree lymphocytes but not granulocytes competed with platelets for filter binding. Precoating of filter layers with individual plasma components showed that hyaluronic acid, plasma type fibronectin, and fibrinogen all increased the binding of leukocytes compared with albumin coating. In conclusion, leukocytes can bind passively to filters in a process which does not require Ca(2+), which is independent of cytoskeletal activation and which may depend on individual plasma components. These results are of importance when new selective cell enrichment or depletion strategies through specific filters are envisaged.

  12. Lymphocytic mastopathy mimicking breast malignancy: a case report.

    PubMed

    Campos, Gabriela Couto Possati; Castro, Melissa Vieira Koch E; de Mattos, Viviane Ferreira Esteves; Pinto, Laura Zaiden Ferreira E; Boechat, Marcia Cristina Bastos; Dos Santos, Alair Augusto Sarmet Moreira Damas

    2014-01-01

    Lymphocytic mastopathy affects both young and middle-aged women and is frequently associated with autoimmune diseases. Diagnosis is done by associating clinical (breast tissue thickening or hardened breast lump), radiological (increased breast density, presence of mass and calcifications), sonographic (nodule with posterior acoustic shadowing), histopathological (fibrosis and lymphocytic infiltrate) and immunohistochemical findings. Lymphocytic mastopathy is a benign entity that may mimic carcinoma. The authors report the case of a patient with lymphocytic mastopathy.

  13. Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi.

    PubMed Central

    Schoenfeld, R; Araneo, B; Ma, Y; Yang, L M; Weis, J J

    1992-01-01

    Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore, the sonicated preparation stimulated the B-cell tumor line CH12.LX to secrete immunoglobulin in the absence of accessory cells. B. burgdorferi also stimulated interleukin-6 production in splenocyte cultures. The observation that B. burgdorferi can stimulate activation of and immunoglobulin production by normal B lymphocytes may directly reflect on the development of arthritis associated with persistent infection by this organism. Images PMID:1730476

  14. B Lymphocyte Homeostasis and BLyS Directed Immunotherapy in Transplantation

    PubMed Central

    Parsons, Ronald F.; Vivek, Kumar; Redfield, Robert R.; Migone, Thi-Sau; Cancro, Michael P.; Naji, Ali; Noorchashm, Hooman

    2010-01-01

    Current strategies for immunotherapy after transplantation are primarily T-lymphocyte directed and effectively abrogate acute rejection. However, the reality of chronic allograft rejection attests to the fact that transplantation tolerance remains an elusive goal. Donor-specific antibodies are considered the primary cause of chronic rejection. When naïve, alloreactive B cells encounter alloantigen and are activated, a resilient “sensitized” state, characterized by the presence of high-affinity antibody, is established. Here, we will delineate findings that support transient B-lymphocyte depletion therapy at the time of transplantation to preempt sensitization by eliminating alloreactive specificities from the recipient B-cell pool (i.e., “repertoire remodeling”). Recent advances in our understanding of B-lymphocyte homeostasis provide novel targets for immunomodulation in transplantation. Specifically, the TNF-related cytokine, BLyS, is the dominant survival factor for “tolerance-susceptible” Transitional and “preimmune” mature Follicular B-cells. The Transitional phenotype is the intermediate through which all newly formed B cells pass before maturing into the Follicular subset, which is responsible for mounting an alloantigen specific antibody response. Systemic BLyS levels dictate the stringency of negative selection during peripheral B cell repertoire development. Thus, targeting BLyS will likely provide an opportunity for repertoire directed therapy to eliminate alloreactive B-cell specificities in transplant recipients; a requirement for the achievement of humoral tolerance and prevention of chronic rejection. In this review the fundamentals of pre-immune B cell selection, homeostasis and activation will be described. Also, new and current B-lymphocyte directed therapy for antibody mediated rejection and the highly sensitized state will be discussed. Overall, our objective will be to propose a rational approach for induction of B cell

  15. [Influence of radiotherapy on lymphocyte stimulation].

    PubMed

    Renner, H; Renner, K H; Hassenstein, E

    1976-08-01

    More than 300 lymphocyte cultures of 12 patients with seminomas were examined during the prophylactic radiotherapy and, in several cases, during an extended period until 20.5 months after the end of the treatment. The object of this study was to find out by measuring the capacity of the lymphocytes to be stimulated in vitro wheather they could be damaged by the radiotherapy. Among other reasons, the above mentioned patients were chosen because they had been submitted to irradiations of vast volumes of lymphatic tissues at a uniform focal dose of 4000 rad. The different opinions expressed in the literature (stimulation decreassed resp. increased resp. unchanged) are reflected by our results in such a way that we did not find a qualitative loss of the capacity to be stimulated cultures. The problem of the different opinions about the capacity of lymphocytes to be stimulated after a radiotherapy appears; among other things, to be based on different examination methods. According to these methods- morphological determination of the relative number of lymphoblasts, synthesis of DNA by fluid scintillation counting, or determination of the number of surviving cells in vitro -different results are obtained. It seems not possible to use the lymphocyte stimulation in vitro as a method of testing clinical sideefects occuring during the characteristics of immunity and radiation biology are not differentiated in a more precise manner.

  16. Lymphocyte Functions in Space - Related Conditions

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    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.

  17. Hydroxyl radical scavengers inhibit lymphocyte mitogenesis.

    PubMed Central

    Novogrodsky, A; Ravid, A; Rubin, A L; Stenzel, K H

    1982-01-01

    Agents that are known to be scavengers of hydroxyl radicals inhibit lymphocyte mitogenesis induced by phorbol myristate acetate (PMA) to a greater extent than they inhibit mitogenesis induced by concanavalin A or phytohemagglutinin. These agents include dimethyl sulfoxide, benzoate, thiourea, dimethylurea, tetramethylurea, L-tryptophan, mannitol, and several other alcohols. Their inhibitory effect is not associated with cytotoxicity. The hydroxyl radical scavengers do not inhibit PMA-dependent amino acid transport in T cells or PMA-induced superoxide production by monocytes. Thus, they do not inhibit the primary interaction of PMA with responding cells. Treatment of peripheral blood mononuclear cells with PMA increased cellular guanylate cyclase in most experiments, and dimethyl sulfoxide tended to inhibit this increase. In addition to inhibition of PMA-induced mitogenesis, hydroxyl radical scavengers markedly inhibited the activity of lymphocyte activating factor (interleukin 1). The differential inhibition of lymphocyte mitogenesis induced by different mitogens appears to be related to the differential macrophage requirements of the mitogens. The data suggest that hydroxyl radicals may be involved in mediating the triggering signal for lymphocyte activation. Some of the hydroxyl radical scavengers are inducers of cellular differentiation,. nd it is possible that their differentiating activity is related to their ability to scavenge free radicals. PMID:6122209

  18. [Enterobacterial antigen in human peripheral blood lymphocytes].

    PubMed

    Faure-Fontenla, M A; García-Tamayo, F

    1989-11-01

    The following study has as prior history the research reports which have shown the existence of an antigenic tissue deposit in gram-negative enterobacteria. The antigens of the enterobacteria have also been found in the lymphocytic membranes and cytoplasm. Since intestinal lymphoid tissue cells can recirculate by means of the thoracic duct to the peripheral venous system, it was proposed that the circulating lymphocytes in healthy people could also contain small amounts of a common enterobacterial antigen. The study was carried out in 15 human venous blood samples, of which the lymphocytic population was separated to later be used in the preparation of 15 alcohol soluble extracts. This material was used for inhibiting the immuno-hemolysis assay in three occasions in order to show the presence of antigens shared by different enterobacterias, using as reference a fraction separated from the LPS of Escherichia coli 08. The results showed that the human lymphocytes also had antigenic determinants common to gram-negative bacteria.

  19. DEXAMETHASONE DEPLETES GAMMA-DELTA T CELLS AND ALTERS THE ACTIVATION STATE AND RESPONSIVENESS OF BOVINE PERIPHERAL BLOOD LYMPHOCYTE SUBPOPULATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Administration of dexamethasone (DEX) to cattle is commonly used in models of stress-induced effects on host defense, including models investigating interactions of microorganisms with their host. Much less is known about the effects of DEX on the adaptive immune response in cattle than in other sp...

  20. Mechanosensitive activation of K+ channel via phospholipase C-induced depletion of phosphatidylinositol 4,5-bisphosphate in B lymphocytes.

    PubMed

    Nam, Joo Hyun; Lee, Hoo-Se; Nguyen, Yen Hoang; Kang, Tong Mook; Lee, Sung Won; Kim, Hye-Young; Kim, Sang Jeong; Earm, Yung E; Kim, Sung Joon

    2007-08-01

    In various types of cells mechanical stimulation of the plasma membrane activates phospholipase C (PLC). However, the regulation of ion channels via mechanosensitive degradation of phosphatidylinositol 4,5-bisphosphate (PIP(2)) is not known yet. The mouse B cells express large conductance background K(+) channels (LK(bg)) that are inhibited by PIP(2). In inside-out patch clamp studies, the application of MgATP (1 mm) also inhibited LK(bg) due to the generation of PIP(2) by phosphoinositide (PI)-kinases. In the presence of MgATP, membrane stretch induced by negative pipette pressure activated LK(bg), which was antagonized by PIP(2) (> 1 microm) or higher concentration of MgATP (5 mm). The inhibition by PIP(2) was partially reversible. However, the application of methyl-beta-cyclodextrin, a cholesterol scavenger disrupting lipid rafts, induced the full recovery of LK(bg) activity and facilitated the activation by stretch. In cell-attached patches, LK(bg) were activated by hypotonic swelling of B cells as well as by negative pressure. The mechano-activation of LK(bg) was blocked by U73122, a PLC inhibitor. Neither actin depolymerization nor the inhibition of lipid phosphatase blocked the mechanical effects. Direct stimulation of PLC by m-3M3FBS or by cross-linking IgM-type B cell receptors activated LK(bg). Western blot analysis and confocal microscopy showed that the hypotonic swelling of WEHI-231 induces tyrosine phosphorylation of PLCgamma2 and PIP(2) hydrolysis of plasma membrane. The time dependence of PIP(2) hydrolysis and LK(bg) activation were similar. The presence of LK(bg) and their stretch sensitivity were also proven in fresh isolated mice splenic B cells. From the above results, we propose a novel mechanism of stretch-dependent ion channel activation, namely, that the degradation of PIP(2) caused by stretch-activated PLC releases LK(bg) from the tonic inhibition by PIP(2).

  1. Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-29

    Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

  2. Subsets of blood, spleen and recirculating lymphocytes in man.

    PubMed Central

    Reinecke, G; Pabst, R

    1983-01-01

    Lymphocyte subpopulations were characterized in human blood and spleens. In addition the spleens were perfused by a closed extracorporeal perfusion system under almost physiological conditions. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. B lymphocytes were classified by their surface immunoglobulin, T lymphocytes and T lymphocyte subsets by cytochemistry, sheep red blood cell rosette formation and in some experiments by monoclonal antibodies. In the blood 71 +/- 4.3% of the lymphocytes were rosette forming cells and 23.3 +/- 3.8% B lymphocytes. In the spleen 49.8 +/- 3.6% were T and 53.3 +/- 2.1% were B lymphocytes. In three spleens the mean number of OKT3+ lymphocytes were 27.6 +/- 7.0% OKT4+ 8.6 +/- 1.4% and OKT8+ 13.7 +/- 2.2%. The ratio of T helper to T suppressor lymphocytes was 0.67 for the spleen and 1.7 for the blood. The lymphocytes released from the perfused spleen showed a similar distribution pattern of surface markers to that of the splenic subpopulations. Images Fig. 1 PMID:6225579

  3. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocytic choriomeningitis virus serological... § 866.3360 Lymphocytic choriomeningitis virus serological reagents. (a) Identification. Lymphocytic choriomeningitis virus serological reagents are devices that consist of antigens and antisera used in...

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

    PubMed

    Escajadillo, C; Binns, R M

    1975-01-01

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

  5. CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs.

    PubMed

    Shiow, Lawrence R; Rosen, David B; Brdicková, Nadezda; Xu, Ying; An, Jinping; Lanier, Lewis L; Cyster, Jason G; Matloubian, Mehrdad

    2006-03-23

    Naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. During immune responses, the egress process can be shut down transiently. When this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. Several mediators of the innate immune system are known to cause shutdown, including interferon alpha/beta (IFN-alpha/beta) and tumour necrosis factor, but the mechanism has been unclear. Here we show that treatment with the IFN-alpha/beta inducer polyinosine polycytidylic acid (hereafter 'poly(I:C)') inhibited egress by a mechanism that was partly lymphocyte-intrinsic. The transmembrane C-type lectin CD69 was rapidly induced and CD69-/- cells were poorly retained in lymphoid tissues after treatment with poly(I:C) or infection with lymphocytic choriomeningitis virus. Lymphocyte egress requires sphingosine 1-phosphate receptor-1 (S1P1), and IFN-alpha/beta was found to inhibit lymphocyte responsiveness to S1P. By contrast, CD69-/- cells retained S1P1 function after exposure to IFN-alpha/beta. In coexpression experiments, CD69 inhibited S1P1 chemotactic function and led to downmodulation of S1P1. In a reporter assay, S1P1 crosslinking led to co-crosslinking and activation of a CD69-CD3zeta chimaera. CD69 co-immunoprecipitated with S1P1 but not the related receptor, S1P3. These observations indicate that CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-alpha/beta, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs.

  6. Mechanism of action of cysteamine in depleting prolactin immunoreactivity

    SciTech Connect

    Sagar, S.M.; Millard, W.J.; Martin, J.B.; Murchison, S.C.

    1985-08-01

    The thiol reagent cysteamine (CSH) depletes anterior pituitary cells of immunoreactive PRL both in vivo and in vitro. The authors examined the hypothesis that CSH affects either the solubility or immunoreactivity of PRL through a mechanism involving thiol-disulfide exchange. Adult female rats were treated with either CSH (300 mg/kg, sc) or an equimolar dose of ethanolamine as a control. Anterior pituitary glands were extracted in 0.1 M sodium borate buffer, pH 9.0. Treatment of pituitary extracts with beta-mercaptoethanol (BME) destroys the immunoreactivity of PRL. However, extraction in the presence of reduced glutathione or CSH of pituitaries of rats treated with CSH restores immunoreactive PRL to control levels. Extracts were also subjected to polyacrylamide gel electrophoresis (PAGE). On gels of pituitary extracts of CSH-treated rats, the band that comigrates with purified PRL is diminished compared to that in ethanolamine-treated controls. However, extraction of the pituitaries in sodium dodecyl sulfate-containing buffer followed by chemical reduction with BME restores the PRL band. Therefore, CSH acts on PRL through a thiol-related mechanism to yield a product that is poorly soluble in aqueous buffer at pH 9 and is poorly immunoreactive. Dispersed anterior pituitary cells in tissue culture were incubated with L-(TVS)methionine to radiolabel newly synthesized peptides. PAGE followed by autoradiography confirmed the above results obtained in vivo.

  7. Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology.

    PubMed

    Udagawa, Tsuyoshi; Farny, Natalie G; Jakovcevski, Mira; Kaphzan, Hanoch; Alarcon, Juan Marcos; Anilkumar, Shobha; Ivshina, Maria; Hurt, Jessica A; Nagaoka, Kentaro; Nalavadi, Vijayalaxmi C; Lorenz, Lori J; Bassell, Gary J; Akbarian, Schahram; Chattarji, Sumantra; Klann, Eric; Richter, Joel D

    2013-11-01

    Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice rescued working memory deficits, demonstrating reversal of this FXS phenotype. Finally, we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function.

  8. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

    Warrington, R.J.; Tse, K.S.

    1979-01-01

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

  9. Lymphocyte transformation studies in drug hypersensitivity.

    PubMed

    Warrington, R J; Tse, K S

    1979-05-05

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

  10. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

    SciTech Connect

    Zana, Marianna . E-mail: mzana@freemail.hu; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Vetro, Agnes; Pakaski, Magdolna; Janka, Zoltan; Kalman, Janos; Szabo, Krisztina; Szucs, Peter; Varkonyi, Agnes; Boda, Krisztina; Rasko, Istvan

    2006-06-30

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

  11. Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

    PubMed Central

    Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

    2015-01-01

    We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

  12. Policies on global warming and ozone depletion

    SciTech Connect

    Green, B.

    1987-04-01

    The recent discovery of a dramatic seasonal drop in the amount of ozone over Antarctica has catalyzed concern for protection of stratospheric ozone, the layer of gas that shields the entire planet from excess ultraviolet radiation. Conservative scientific models predict about a 5% reduction in the amount of global ozone by the middle of the next century, with large local variations. The predicted global warming from increased emissions of greenhouse gases will also have differing effects on local climate and weather conditions and consequently on agriculture. Although numerous uncertainties are associated with both ozone depletion and a global warming, there is a consensus that world leaders need to address the problems. The US Congress is now beginning to take note of the task. In this article, one representative outlines some perceptions of the problems and the policy options available to Congress.

  13. Arctic Ozone Depletion from UARS MLS Measurements

    NASA Technical Reports Server (NTRS)

    Manney, G. L.

    1995-01-01

    Microwave Limb Sounder (MLS) measurements of ozone during four Arctic winters are compared. The evolution of ozone in the lower stratosphere is related to temperature, chlorine monoxide (also measured by MLS), and the evolution of the polar vortex. Lagrangian transport calculations using winds from the United Kingdom Meteorological Office's Stratosphere-Troposphere Data Assimilation system are used to estimate to what extent the evolution of lower stratospheric ozone is controlled by dynamics. Observations, along with calculations of the expected dynamical behavior, show evidence for chemical ozone depletion throughout most of the Arctic lower stratospheric vortex during the 1992-93 middle and late winter, and during all of the 1994-95 winter that was observed by MLS. Both of these winters were unusually cold and had unusually cold and had unusually strong Arctic polar vortices compared to meteorological data over the past 17 years.

  14. Tylosin depletion from edible pig tissues.

    PubMed

    Prats, C; El Korchi, G; Francesch, R; Arboix, M; Pérez, B

    2002-12-01

    The depletion of tylosin from edible pig tissues was studied following 5 days of intramuscular (i.m.) administration of 10 mg/kg of tylosin to 16 crossbreed pigs. Animals were slaughtered at intervals after treatment and samples of muscle, kidney, liver, skin+fat, and injection site were collected and analysed by high-performance liquid chromatography (HPLC). Seven days after the completion of treatment, the concentration of tylosin in kidney, skin+fat, and at the injection site was higher than the European Union maximal residue limit (MRL) of 100 microg/kg. Tylosin residues in all tissues were below the quantification limit (50 microg/kg) at 10 and 14 days post-treatment.

  15. Processing depleted uranium quad alloy penetrator rods

    SciTech Connect

    Bokan, S.L.

    1987-02-19

    Two depleted uranium (DU) quad alloys were cast, extruded and rolled to produce penetrator rods. The two alloy combinations were (1) 1 wt % molybdenum (Mo), 1 wt % niobium (Nb), and 0.75 wt % titanium (Ti); and (2) 1 wt % tantalum (Ta), 1 wt % Nb, and 0.75 wt % Ti. This report covers the processing and results with limited metallographic information available. The two alloys were each vacuum induction melted (VIM) into an 8-in. log, extruded into a 3-in. log, then cut into 4 logs and extruded at 4 different temperatures into 0.8-in. bars. From the 8 conditions (2 alloys, 4 extrusion temperatures each), 10 to 13 16-in. rods were cut for rolling and swaging. Due to cracking problems, the final processing changed from rolling and swaging to limited rolling and heat treating. The contracted work was completed with the delivery of 88 rods to Dr. Zabielski. 28 figs.

  16. Chemical and radiological toxicity of depleted uranium.

    PubMed

    Sztajnkrycer, Matthew D; Otten, Edward J

    2004-03-01

    A by-product of the uranium enrichment process, depleted uranium (DU) contains approximately 40% of the radioactivity of natural uranium yet retains all of its chemical properties. After its use in the 1991 Gulf War, public concern increased regarding its potential radiotoxicant properties. Whereas in vitro and rodent data have suggested the potential for uranium-induced carcinogenesis, human cohort studies assessing the health effects of natural and DU have failed to validate these findings. Heavy-metal nephrotoxicity has not been noted in either animal studies or Gulf War veteran cohort studies despite markedly elevated urinary uranium excretion. No significant residual environmental contamination has been found in geographical areas exposed to DU. As such, although continued surveillance of exposed cohorts and environments (particularly water sources) are recommended, current data would support the position that DU poses neither a radiological nor chemical threat.

  17. Anxiety, ego depletion, and sports performance.

    PubMed

    Englert, Chris; Bertrams, Alex

    2012-10-01

    In the present article, we analyzed the role of self-control strength and state anxiety in sports performance. We tested the hypothesis that self-control strength and state anxiety interact in predicting sports performance on the basis of two studies, each using a different sports task (Study 1: performance in a basketball free throw task, N = 64; Study 2: performance in a dart task, N = 79). The patterns of results were as expected in both studies: Participants with depleted self-control strength performed worse in the specific tasks as their anxiety increased, whereas there was no significant relation for participants with fully available self-control strength. Furthermore, different degrees of available self-control strength did not predict performance in participants who were low in state anxiety, but did in participants who were high in state anxiety. Thus increasing self-control strength could reduce the negative anxiety effects in sports and improve athletes' performance under pressure.

  18. Modelling chemical depletion profiles in regolith

    USGS Publications Warehouse

    Brantley, S.L.; Bandstra, J.; Moore, J.; White, A.F.

    2008-01-01

    Chemical or mineralogical profiles in regolith display reaction fronts that document depletion of leachable elements or minerals. A generalized equation employing lumped parameters was derived to model such ubiquitously observed patterns:C = frac(C0, frac(C0 - Cx = 0, Cx = 0) exp (??ini ?? over(k, ??) ?? x) + 1)Here C, Cx = 0, and Co are the concentrations of an element at a given depth x, at the top of the reaction front, or in parent respectively. ??ini is the roughness of the dissolving mineral in the parent and k???? is a lumped kinetic parameter. This kinetic parameter is an inverse function of the porefluid advective velocity and a direct function of the dissolution rate constant times mineral surface area per unit volume regolith. This model equation fits profiles of concentration versus depth for albite in seven weathering systems and is consistent with the interpretation that the surface area (m2 mineral m- 3 bulk regolith) varies linearly with the concentration of the dissolving mineral across the front. Dissolution rate constants can be calculated from the lumped fit parameters for these profiles using observed values of weathering advance rate, the proton driving force, the geometric surface area per unit volume regolith and parent concentration of albite. These calculated values of the dissolution rate constant compare favorably to literature values. The model equation, useful for reaction fronts in both steady-state erosional and quasi-stationary non-erosional systems, incorporates the variation of reaction affinity using pH as a master variable. Use of this model equation to fit depletion fronts for soils highlights the importance of buffering of pH in the soil system. Furthermore, the equation should allow better understanding of the effects of important environmental variables on weathering rates. ?? 2008.

  19. Transfer of antigenic macromolecules from macrophages to lymphocytes

    PubMed Central

    Bona, C.; Anteunis, A.; Robineaux, R.; Astesano, A.

    1972-01-01

    In an in vitro autologous system, studies were carried out on the transfer of either biosynthetically-labelled [14C]Salmonella enteritidis endotoxin or [125I]Maia squinado haemocyanin from macrophages to lymphocytes. When cultured 1 hour in vitro, lymphocytes adhered to autologous macrophages, forming lymphocyte-macrophage islands (LMI). Quantitative data obtained from stained thick sections showed that 1.8 per cent of the lymphocytes had adhered to macrophages with ingested [14C]endotoxin while 0.6 per cent of the lymphocytes adhered to macrophages with ingested [125I]haemocyanin. The presence of antigen macromolecules was observed mainly within lymphocytes adhering to macrophages with ingested antigens, i.e. at the level of LMI. On the other hand, autoradiography carried out on the same thick sections, showed that 0.20 per cent of the lymphocyte population in LMI possess silver grains. High resolution autoradiographic pictures of thin sections, showed a peculiar localization of silver grains in LMI lymphocytes: about 80 per cent of the radioactivity was found within lymphocytic nuclei and the remainder either on the cellular membrane or free in the cytoplasm. The disappearance of radioactivity from the LMI-located macrophage membranes (where lymphocytes contain silver grains) as well as the regular inhibition of antigen transfer occurring after pronase treatment of the macrophage which contained ingested antigen, strongly suggest that antigen bound to macrophage membrane was transferred to lymphocytes. As pretreatment of lymphocytes with anti-Ig serum resulted in regular inhibition of antigen transfer, it appears that the Ig receptors of lymphocyte membranes play an important role in the transfer mechanism. Combined technique, i.e. autoradiography and the peroxidase method for revealing Ig bound to lymphocyte membranes, showed that silver grains occurred only within lymphocytes displaying peroxidase-positive membrane. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID

  20. In-Vivo Activated T-Cell Depletion to Prevent GVHD

    ClinicalTrials.gov

    2014-09-26

    Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplasia; Lymphoma, Non-Hodgkin's; Mantle-Cell Lymphoma; Hodgkin's Disease; Multiple Myeloma; Myelofibrosis

  1. Spotlight on ibrutinib and its potential in frontline treatment of chronic lymphocytic leukemia

    PubMed Central

    Khan, Maliha; Gibbons, Jamie L; Ferrajoli, Alessandra

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the adult population. Current efforts are focused on better understanding the intricate pathophysiology of the disease to develop successful targeted therapies. Ibrutinib is emerging as an important agent in this new age of targeted treatment for CLL. As a Bruton’s tyrosine kinase inhibitor, it blocks the signaling pathway that malignant B-lymphocytes need for growth and maturation. Ibrutinib’s role in therapy was further expanded recently when the US Food and Drug Administration approved its use in both frontline and salvage treatment for patients with CLL. This review assesses the effectiveness of ibrutinib in the frontline setting, its efficacy in various types of patients with CLL, and its safety and tolerability.

  2. Adenosine deaminase activity in serum, erythrocytes and lymphocytes of rats infected with Leptospira icterohaemorrhagiae.

    PubMed

    Tonin, Alexandre A; Pimentel, Victor C; da Silva, Aleksandro S; de Azevedo, Maria Isabel; Souza, Viviane C G; Wolkmer, Patrícia; Rezer, João F P; Badke, Manoel R T; Leal, Daniela B R; Schetinger, Maria Rosa C; Monteiro, Silvia G; Lopes, Sonia T A

    2012-04-01

    Leptospirosis is a systemic disease of humans and domestic animals, mainly dogs, cattle and swine. The course of human leptospirosis varies from mild to severe fatal forms and the most severe form of human leptospirosis is principally caused by Leptospira interrogans serovar icterohaemorrhagiae (L. icterohaemorrhagiae). The enzyme adenosine deaminase (ADA) plays an important role in the production and differentiation of blood cells. The aim of this study was to evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats infected with L. icterohaemorrhagiae, as compared with non-infected rats. Twenty-four adult rats, divided into two uniform groups (A and B) were used for the enzymatic assays. The animals in Group B were inoculated intraperitoneally with 2×10(8) leptospires/rat, and the rodents in Group A (control) were not-inoculated. Blood collection was performed on days 5 and 15 post-infection (PI) and the blood used to assess the ADA activity. The infection by L.icterohaemorrhagiae altered erythrocyte count, hemoglobin concentration and hematocrit, causing a decrease in all these parameters on day 15 PI. Lymphocytes decreased significantly on day 15 PI, and ADA activity in serum was inhibited in infected rats on days 5 and 15 PI and its activity in erythrocytes were increased on day 5 PI. On day 5 PI, we found an increase in ADA activity in erythrocytes of infected rats. No correlation was observed between hematocrit and erythrocyte ADA activity on days 5 and 15 PI. The ADA activity was inhibited in rats infected on day 15 PI. A positive correlation (r(2)=60) was also observed between the number of lymphocytes and ADA activity in lymphocytes on day 15 PI (P<0.05). In conclusion, our results showed that the ADA activity is altered in serum, lymphocytes and erythrocytes in experimental infection by L.icterohaemorrhagiae in rats, concomitantly with hematological parameters.

  3. The Cell Wall and Membrane of Cryptococcus neoformans Possess a Mitogen for Human T Lymphocytes

    PubMed Central

    Mody, Christopher H.; Wood, Cynthia J.; Syme, Rachel M.; Spurrell, Jason C. L.

    1999-01-01

    The mechanism of human T-lymphocyte activation by the pathogenic yeast Cryptococcus neoformans has not been established. Previous investigations have suggested that C. neoformans contains a mitogen for T lymphocytes, while other investigators have attributed lymphocyte proliferation in vitro to a recall antigen. Because of the potential importance of the mechanism of T-cell activation for our understanding of the immune response to C. neoformans, the present studies were performed to determine whether C. neoformans contains a mitogen for T lymphocytes. C. neoformans stimulates fetal blood lymphocytes to proliferate and stimulates proliferation of CD45RA+ cells from adults, indicating that it stimulates naive T cells. The T-cell response to C. neoformans was dependent upon the presence of accessory cells. However, allogeneic cells were sufficient for accessory cell function, indicating that the response was not major histocompatibility complex restricted. The percentage of T cells in the cell cycle was higher than that with the recall antigen tetanus toxoid but lower than that with the mitogenic lectin phytohemagglutinin A or the superantigen Staphylococcus enterotoxin B. Precursor frequency analysis established that 1 in 7,750 ± 2,270 T cells proliferated in response to the cryptococcal cell wall and membrane. Compared to the case for most mitogens or superantigens, the proliferative response is late and the number of T cells that enter the cell cycle and the precursor frequency are low, indicating that the mitogenic effect is modest. However, the mitogenic effect of C. neoformans should be considered when interpreting the immune response to C. neoformans, since even weak mitogens can have profound effects on host defense. PMID:9916111

  4. Brief mindfulness induction could reduce aggression after depletion.

    PubMed

    Yusainy, Cleoputri; Lawrence, Claire

    2015-05-01

    Many experiments have shown that one's ability to refrain from acting on aggressive impulses is likely to decrease following a prior act of self-control. This temporary state of self-control failure is known as ego-depletion. Although mindfulness is increasingly used to treat and manage aggressive behaviour, the extent to which mindfulness may counteract the depletion effect on aggression is yet to be determined. This study (N=110) investigated the effect of a laboratory induced one-time mindfulness meditation session on aggression following depletion. Aggression was assessed by the intensity of aversive noise blast participants delivered to an opponent on a computerised task. Depleted participants who received mindfulness induction behaved less aggressively than depleted participants with no mindfulness induction. Mindfulness also improved performance on a second measure of self-control (i.e., handgrip perseverance); however, this effect was independent of depletion condition. Motivational factors may help explain the dynamics of mindfulness, self-control, and aggression.

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

    PubMed

    Cina, Stephen J; Perper, Joshua A

    2009-09-01

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

  6. Effects of tryptophan depletion and a simulated alcohol binge on impulsivity

    PubMed Central

    Dougherty, Donald M.; Mullen, Jillian; Hill-Kapturczak, Nathalie; Liang, Yuanyuan; Karns, Tara E.; Lake, Sarah L.; Mathias, Charles W.; Roache, John D.

    2015-01-01

    Background Researchers have suggested that binge drinkers experience disproportionate increases in impulsivity during the initial period of drinking, leading to a loss of control over further drinking, and that serotonergic mechanisms may underlie such effects. Methods We examined the effects of a simulated-alcohol binge and tryptophan depletion on three types of impulsivity: response initiation (IMT task), response inhibition (GoStop task), and delay discounting (SKIP task), and tested whether observed effects were related to “real world” binge drinking. 179 adults with diverse drinking histories completed a within-subject crossover design over 4 experimental days. Each day, participants underwent one of four test conditions: tryptophan depletion/alcohol, tryptophan depletion/placebo, tryptophan balanced control/alcohol, or tryptophan balanced control/placebo. The simulated binge involved consuming 0.3 g/kg of alcohol at 5, 6, and 7 hours after consuming the tryptophan depletion/balanced mixture. Impulsivity was measured before and after each drink. Results Relative to the placebo beverage condition, when alcohol was consumed, impulsive responding was increased at moderate and high levels of intoxication on the IMT and GoStop, but only at high levels of intoxication on the SKIP. Tryptophan depletion had no effect on impulsivity measured under either placebo or alcohol beverage conditions. Effects of alcohol and tryptophan manipulations on impulsivity were unrelated to patterns of binge drinking outside the laboratory. Conclusion The effects of alcohol consumption on impulsivity depend on the component of impulsivity being measured and the dose of alcohol consumed. Such effects do not appear to be a result of reduced serotonin synthesis. Additionally, “real world” binge drinking behaviors were unrelated to behavioral changes observed in the laboratory. PMID:25730415

  7. Pseudomonas aeruginosa Exoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

    PubMed Central

    Bruno, Tony F.; Buser, Deborah E.; Syme, Rachel M.; Woods, Donald E.; Mody, Christopher H.

    1998-01-01

    Virtually all cystic fibrosis (CF) patients become infected with Pseudomonas aeruginosa, and once the infection is established, the organism is rarely cleared. One of the P. aeruginosa virulence factors, exoenzyme S, has been shown to correlate with increased morbidity and mortality both in rat models of chronic pulmonary inflammation and in human CF patients. It has previously been shown that exoenzyme S is a potent stimulus for the proliferation of T cells in greater than 95% of adults, which could contribute to the pathogenesis of CF. The goal of this study was to determine the mechanism of T-cell stimulation by exoenzyme S in an effort to shed light on the immune response and contribute to understanding its role in P. aeruginosa pathogenesis. The current studies demonstrate that exoenzyme S stimulates naive T cells, since fetal blood lymphocytes proliferated and adult lymphocytes that expressed CD45RA proliferated. The percentage of T cells activated by exoenzyme S after a 4-h culture (as measured by CD69 surface expression) was intermediate in magnitude compared to levels induced by a panel of superantigens and mitogens. To determine the mechanism of activation, the requirement for accessory cells was investigated. The proliferative response to exoenzyme S was dependent on the presence of accessory cells but was not blocked by an anti-DR antibody. Exoenzyme S activated both CD4+ and CD8+ T cells, but CD4+ T cells were preferentially activated. The Vβ repertoire of donor T cells showed no preferential activation or preferential expansion after stimulation by exoenzyme S, suggesting that it is not a superantigen. Taken together, our data suggest that exoenzyme S is a T-cell mitogen but not a superantigen. Activation of a large percentage of T lymphocytes by exoenzyme S may produce a lymphocyte-mediated inflammatory response that should be considered in the pathogenesis of CF. PMID:9632568

  8. ELEMENTAL DEPLETIONS IN THE MAGELLANIC CLOUDS AND THE EVOLUTION OF DEPLETIONS WITH METALLICITY

    SciTech Connect

    Tchernyshyov, Kirill; Meixner, Margaret; Seale, Jonathan; Fox, Andrew; Friedman, Scott D.; Dwek, Eli; Galliano, Frédéric

    2015-10-01

    We present a study of the composition of gas and dust in the Large and Small Magellanic Clouds (LMC and SMC) using UV absorption spectroscopy. We measure P ii and Fe ii along 84 spatially distributed sightlines toward the MCs using archival Far Ultraviolet Spectroscopic Explorer observations. For 16 of those sightlines, we also measure Si ii, Cr ii, and Zn ii from new Hubble Space Telescope Cosmic Origins Spectrograph observations. We analyze these spectra using a new spectral line analysis technique based on a semi-parametric Voigt profile model. We have combined these measurements with H i and H{sub 2} column densities and reference stellar abundances from the literature to derive gas-phase abundances, depletions, and gas-to-dust ratios (GDRs). Of our 84 P and 16 Zn measurements, 80 and 13, respectively, are depleted by more than 0.1 dex, suggesting that P and Zn abundances are not accurate metallicity indicators at and above the metallicity of the SMC. Si, Cr, and Fe are systematically less depleted in the SMC than in the Milky Way (MW) or LMC. The minimum Si depletion in the SMC is consistent with zero. We find GDR ranges of 190–565 in the LMC and 480–2100 in the SMC, which is broadly consistent with GDRs from the literature. These ranges represent actual location to location variation and are evidence of dust destruction and/or growth in the diffuse neutral phase of the interstellar medium. Where they overlap in metallicity, the gas-phase abundances of the MW, LMC, and SMC and damped Lyα systems evolve similarly with metallicity.

  9. The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis

    PubMed Central

    Gao, Jie; Buckley, Shannon M; Cimmino, Luisa; Guillamot, Maria; Strikoudis, Alexandros; Cang, Yong; Goff, Stephen P; Aifantis, Iannis

    2015-01-01

    Little is known on post-transcriptional regulation of adult and embryonic stem cell maintenance and differentiation. Here we characterize the role of Ddb1, a component of the CUL4-DDB1 ubiquitin ligase complex. Ddb1 is highly expressed in multipotent hematopoietic progenitors and its deletion leads to abrogation of both adult and fetal hematopoiesis, targeting specifically transiently amplifying progenitor subsets. However, Ddb1 deletion in non-dividing lymphocytes has no discernible phenotypes. Ddb1 silencing activates Trp53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis. The abrogation of hematopoietic progenitor cells can be partially rescued by simultaneous deletion of Trp53. Conversely, depletion of DDB1 in embryonic stem cell (ESC) leads to differentiation albeit negative effects on cell cycle and apoptosis. Mass spectrometry reveals differing protein interactions between DDB1 and distinct DCAFs, the substrate recognizing components of the E3 complex, between cell types. Our studies identify CUL4-DDB1 complex as a novel post-translational regulator of stem and progenitor maintenance and differentiation. DOI: http://dx.doi.org/10.7554/eLife.07539.001 PMID:26613412

  10. Gas generation matrix depletion quality assurance project plan

    SciTech Connect

    1998-05-01

    The Los Alamos National Laboratory (LANL) is to provide the necessary expertise, experience, equipment and instrumentation, and management structure to: Conduct the matrix depletion experiments using simulated waste for quantifying matrix depletion effects; and Conduct experiments on 60 cylinders containing simulated TRU waste to determine the effects of matrix depletion on gas generation for transportation. All work for the Gas Generation Matrix Depletion (GGMD) experiment is performed according to the quality objectives established in the test plan and under this Quality Assurance Project Plan (QAPjP).

  11. Producing, Importing, and Exporting Ozone-Depleting Substances

    EPA Pesticide Factsheets

    Overview page provides links to information on producing, importing, and exporting ozone-depleting substances, including information about the HCFC allowance system, importing, labeling, recordkeeping and reporting.

  12. Regret causes ego-depletion and finding benefits in the regrettable events alleviates ego-depletion.

    PubMed

    Gao, Hongmei; Zhang, Yan; Wang, Fang; Xu, Yan; Hong, Ying-Yi; Jiang, Jiang

    2014-01-01

    This study tested the hypotheses that experiencing regret would result in ego-depletion, while finding benefits (i.e., "silver linings") in the regret-eliciting events counteracted the ego-depletion effect. Using a modified gambling paradigm (Experiments 1, 2, and 4) and a retrospective method (Experiments 3 and 5), five experiments were conducted to induce regret. Results revealed that experiencing regret undermined performance on subsequent tasks, including a paper-and-pencil calculation task (Experiment 1), a Stroop task (Experiment 2), and a mental arithmetic task (Experiment 3). Furthermore, finding benefits in the regret-eliciting events improved subsequent performance (Experiments 4 and 5), and this improvement was mediated by participants' perceived vitality (Experiment 4). This study extended the depletion model of self-regulation by considering emotions with self-conscious components (in our case, regret). Moreover, it provided a comprehensive understanding of how people felt and performed after experiencing regret and after finding benefits in the events that caused the regret.

  13. If ego depletion cannot be studied using identical tasks, it is not ego depletion.

    PubMed

    Lange, Florian

    2015-01-01

    The hypothesis that human self-control capacities are fueled by glucose has been challenged on multiple grounds. A recent study by Lange and Eggert adds to this criticism by presenting two powerful but unsuccessful attempts to replicate the effect of sugar drinks on ego depletion. The dual-task paradigms employed in these experiments have been criticized for involving identical self-control tasks, a methodology that has been argued to reduce participants' willingness to exert self-control. The present article addresses this criticism by demonstrating that there is no indication to believe that the study of glucose effects on ego depletion should be restricted to paradigms using dissimilar acts of self-control. Failures to observe such effects in paradigms involving identical tasks pose a serious problem to the proposal that self-control exhaustion might be reversed by rinsing or ingesting glucose. In combination with analyses of statistical credibility, the experiments by Lange and Eggert suggest that the influence of sugar on ego depletion has been systematically overestimated.

  14. Bioluminescent assay for human lymphocyte blast transformation.

    PubMed

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

    1995-05-01

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

  15. Effect of weightlessness on lymphocyte proliferation

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1981-01-01

    An experiment to study the effect of weightlessness on lymphocyte proliferation to detect possible alteration of the cells responsible for the immune response during long-duration space flights is described. Human lymphocytes in culture medium will be delivered shortly before launch in an incubator which will be kept at 37C. Mitogen will be added to the culture. A control without mitogen will be run in parallel. After 70 hours of incubation, radioactive thymidine will be added. After two hours, cellular activity will be stopped by fixation and incubator power switched off. Later, the amount of incorporated thymidine will be determined and the cell morphology and the distribution of cell organelles will be investigated.

  16. Metabolism pathways in chronic lymphocytic leukemia.

    PubMed

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

    2016-01-01

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

  17. Stretched cell cycle model for proliferating lymphocytes

    PubMed Central

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

    2014-01-01

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

  18. Obinutuzumab for previously untreated chronic lymphocytic leukemia.

    PubMed

    Abraham, Jame; Stegner, Mark

    2014-04-01

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

  19. Lymphocyte transformation in presumed ocular histoplasmosis

    SciTech Connect

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

    1981-08-01

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

  20. Early deficit of lymphocytes in Wiskott–Aldrich syndrome: possible role of WASP in human lymphocyte maturation

    PubMed Central

    PARK, J Y; KOB, M; PRODEUS, A P; ROSEN, F S; SHCHERBINA, A; REMOLD-O'DONNELL, E

    2004-01-01

    Wiskott–Aldrich syndrome (WAS) is an X-linked platelet/immunodeficiency disease. The affected gene encodes WASP, a multidomain protein that regulates cytoskeletal assembly in blood cells. Patients have recurring infections, and their lymphocytes exhibit deficient proliferative responses in vitro. We report an evaluation of peripheral blood lymphocytes of 27 WAS patients, aged one month to 55 years. Whereas NK cells were normal, a significant deficit of T and B lymphocytes was observed. The number of lymphocytes was already decreased in infant patients, suggesting deficient output. Both CD4 and CD8 T lymphocytes were affected; the decrease was most pronounced for naïve T cells. Naïve CD4 lymphocytes of patients showed normal expression of Bcl-2, and Ki-67, and normal survival in vitro, suggesting that their in vivo survival and proliferation are normal. The collective data suggest that the patients’ lymphocyte deficit results from deficient output, likely due to abnormal lymphocyte maturation in the thymus and bone marrow. We propose that WASP plays an important role not only in the function of mature T lymphocytes, but also in the maturation of human T and B lymphocytes and that impaired lymphocyte maturation is central to the aetiology of WAS immunodeficiency. PMID:15030520

  1. Genotoxic effects of borax on cultured lymphocytes.

    PubMed

    Pongsavee, Malinee

    2009-03-01

    The effect of borax on human chromosomes was analyzed in this study. Venous blood from 30 male students at Thammasat University, Thailand (age 18-25 years) was collected for lymphocyte cell cultures. This experiment was divided into two groups: the first group was the control group and the second group was the experimental group. The lymphocyte cells in the control group were cultured without borax. The experimental group was divided into four subgroups. The lymphocyte cells in each experimental subgroup were cultured with different concentrations of borax (0.1 mg/ml, 0.15 mg/ml, 0.2 mg/ml and 0.3 mg/ml). Human chromosomes were studied for abnormalities through Giemsa-staining and G-banding. The results show that the numbers of metaphase plates (the metaphase plate which contained 46 chromosomes; 46, XY) and metaphase chromosomes were reduced when lymphocyte cells were cultured with 0.15 mg/ml (57.2%), 0.2 mg/ml (50.8%) and 0.3 mg/ml (42.3%) concentrations of borax. There was a statistically significant difference between the control and experimental subgroups (p < 0.05). Sister chromatid separation was found in the 0.3 mg/ml borax concentration experimental subgroup. This shows that borax (at 0.15, 0.2 and 0.3 mg/ml concentrations) affects the cell and human chromosomes (both numerical and structural abnormalities). Borax may cause human chromosome abnormalities and lead to genetic defects.

  2. Low lymphocyte count and cardiovascular diseases.

    PubMed

    Núñez, J; Miñana, G; Bodí, V; Núñez, E; Sanchis, J; Husser, O; Llàcer, A

    2011-01-01

    Inflammation plays a crucial pathophysiological role in the entire continuum of the atherosclerotic process, from its initiation, progression, and plaque destabilization leading ultimately to an acute coronary event. Furthermore, once the clinical event has occurred, inflammation also influences the left ventricular remodelling process. Under the same paradigm, there is evidence that lymphocytes play an important role in the modulation of the inflammatory response at every level of the atherosclerotic process. Low lymphocyte count (LLC) is a common finding during the systemic inflammatory response, and clinical and animal studies suggest that LCC plays a putative role in accelerated atherosclerosis. For instance, there is recent evidence that LLC is associated with worse outcomes in patients with heart failure, chronic ischemic heart disease and acute coronary syndromes. Further indirect evidence supports the pathologic role of LLC related to the fact that 1) lymphopenia--due to a decreased count of lymphocyte T cells--normally occurs as a part of the human ageing process, and 2) increased incidence of cardiovascular events has been reported in conditions where lymphopenia is common, such as renal transplant recipients, human immunodeficiency virus infection, survivors of nuclear disasters and autoimmune diseases. The aim of the present article is to review: a) the pathophysiological mechanisms that have been proposed for the observed association between LLC and cardiovascular diseases (CVD), b) the available evidence regarding the diagnostic and prognostic role attributable to LLC in patients with CVD, and; c) the potential therapeutic implications of these findings.

  3. [Phenotypic and functional diversity of B lymphocytes].

    PubMed

    Santos-Argumedo, Leopoldo

    2015-01-01

    For many years, it has been considered that the function of B cells is only to serve as precursors of antibody-producing plasma cells; however, this simplistic view has been challenged in the past thirty years. The first big surprise came during the seventies, when it was shown that B lymphocytes are not a homogeneous population, but is made up of various subpopulations with different origin and functions, including both innate and acquired immunity. During the eighties, it was discovered that B cells are an important source of cytokines, extending its functions from antigen presentation to cooperation with T cells. From the year two thousand, it is clear that B cells are, functionally speaking, as heterogeneous as T lymphocytes, extending its functions to the regulation of the immune response. The story does not end yet, as they continue to discover new features that will have to be incorporated into the main body of knowledge about the mechanisms by which the immune response works. Thus, we can conclude by congratulating the B lymphocytes by these first 50 years and we can predict at least another 50 of robust growth.

  4. Microgravity and Cellular Consequences in Lymphocyte Function

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Sundaresan, Alamelu

    2004-01-01

    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

  5. Sudden unexpected death associated with lymphocytic thyroiditis.

    PubMed

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

    2007-04-01

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

  6. [Influence of radiotherapy on lymphocyte subpopulations].

    PubMed

    Ceschia, T; Beorchia, A; Guglielmi, R; Mandoliti, G; Fongione, S; Cereghini, M; Tonutti, E; Sala, P G; Pizzi, G

    1991-04-01

    The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.

  7. Predictive Value of Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Patients with Coronary Slow Flow

    PubMed Central

    Çetin, Mustafa; Kiziltunc, Emrullah; Elalmış, Özgül Uçar; Çetin, Zehra Güven; Demirçelik, Muhammed Bora; Çiçekçioğlu, Hülya; Kurtul, Alparslan; Özkan, Selçuk; Avan, Candan Mansuroğlu; Örnek, Ender; Ulusoy, Feridun Vasfi

    2016-01-01

    Background Increased microvascular resistance due to chronic inflammation is assumed to be one of the mechanisms associated with coronary slow flow (CSF). Previous studies have shown that the platelet-to-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation for various diseases. In this study we aimed to evaluate the relationship between CSF and PLR-NLR. Methods Seventy-eight patients with CSF and 50 patients with normal coronary flow were enrolled into this study. The study subjects underwent medical examination and testing, after which their platelet-to-lymphocyte ratios and NLR values were calculated. An independent observer measured the coronary flow rate by Thrombolysis in Myocardial Infarction Frame Count (TFC) method. The platelet-to-lymphocyte ratio and NLR values were compared between the groups and correlation analysis was performed to explore the relationship between mean TFC with PLR and NLR. Results Platelet-to-lymphocyte ratio and NLR values were significantly higher in patients with CSF (p < 0.001). There was a positive significant correlation between TFC with NLR and PLR (Spearman’s Rho: 0.59, p < 0.001 and Spearman’s Rho: 0.30, p = 0.001, respectively). Multivariate logistic regression analysis revealed that NLR is the one independent predictor for CSF. Conclusions This study demonstrated an association between CSF and PLR-NLR. Although the exact mechanism could not be explained, our findings support the possible role of inflammation in CSF physiopathology. PMID:27274171

  8. Thermal stress depletes energy reserves in Drosophila

    PubMed Central

    Klepsatel, Peter; Gáliková, Martina; Xu, Yanjun; Kühnlein, Ronald P.

    2016-01-01

    Understanding how environmental temperature affects metabolic and physiological functions is of crucial importance to assess the impacts of climate change on organisms. Here, we used different laboratory strains and a wild-caught population of the fruit fly Drosophila melanogaster to examine the effect of temperature on the body energy reserves of an ectothermic organism. We found that permanent ambient temperature elevation or transient thermal stress causes significant depletion of body fat stores. Surprisingly, transient thermal stress induces a lasting “memory effect” on body fat storage, which also reduces survivorship of the flies upon food deprivation later after stress exposure. Functional analyses revealed that an intact heat-shock response is essential to protect flies from temperature-dependent body fat decline. Moreover, we found that the temperature-dependent body fat reduction is caused at least in part by apoptosis of fat body cells, which might irreversibly compromise the fat storage capacity of the flies. Altogether, our results provide evidence that thermal stress has a significant negative impact on organismal energy reserves, which in turn might affect individual fitness. PMID:27641694

  9. Ozone depletion: 20 Years after the alarm

    SciTech Connect

    Not Available

    1994-08-15

    Scientific curiosity in 1973 led to the challenge of determining the ultimate atmospheric fate of the chlorofluoromethanes, CFC-11 (CCl[sub 3]F) and CFC-12 (CCl[sub 2]F[sub 2]), whose presence at measurable levels in surface air had been detected only two years earlier. In retrospect, the decision to pursue the chemistry of CFC molecules to their final destruction and beyond foreordained an unusual outcome because CFCs are chemically inert and easily survive under almost all natural conditions. By midsummer 1994, the world is well on its way in transition to a CFC-free economy, although not yet to a CFC-free atmosphere. The rates of increase in atmospheric concentration for the three major CFCs (CFC-11, -12, and -113) have all slowed markedly in response to the restrictions of the revised Montreal protocol. Because of their long lifetimes, however, significant but gradually diminishing quantities of CFCs will remain in the atmosphere throughout the 21st century. Atomic chlorine will continue to be released into the stratosphere as long as CFCs persist, and ozone depletion will follow. The existence of the Montreal protocol and the agreement among industrial, governmental, and university scientists on its wisdom offers considerable promise for the handling of future global environmental problems.

  10. Ichnologic signature of oxygen-depleted deposits

    SciTech Connect

    Ekdale, A.A.; Mason, T.R.

    1987-05-01

    The sedimentologic record of oxygen-poor depositional environments commonly includes trace fossils, especially those produced by deposit-feeding organisms that must have had broad oxygen tolerances. Endostratal fodinichnial and pascichnial traces indicate lack of oxygen within the substrate. Complex fodinichnia, such as Chondrites and Zoophycos, may form in anoxic sediment some distance below the water-sediment interface. The deposit-feeding animals can circulate oxygenated bottom water from the sea floor down through semipermanent shafts to permit respiration while they feed on unoxidized organic matter in the subsurface. Endostratal pascichnia, such as Helminthoida and Spirophycus, typically lack a continuous connection with the water-sediment interface, so interstitial water cannot be totally devoid of oxygen or else the animals cannot respire. However, endostratal pascichnia normally do not occur in oxidized sediment where digestible organic detritus has decomposed completely. In totally oxidized substrates, which typify higher energy depositional environments, permanent dwellings (domichnia) of filter-feeding organisms predominate. The ichnologic signature of oxygen-depleted deposits is a very high-density, very low-diversity association of deposit-feeding trace fossils. They suggest an oxygen-controlled trace fossil model in which increasing oxygen concentration of the interstitial water parallels a transition from fodinichnia-dominated through pascichnia-dominated to domichnia-dominated trace fossil associations. This model provides an alternative to the more traditional depth-controlled trace fossil distribution model in certain situations.

  11. Levels of depleted uranium in Kosovo soils.

    PubMed

    Sansone, U; Stellato, L; Jia, G; Rosamilia, S; Gaudino, S; Barbizzi, S; Belli, M

    2001-01-01

    The United Nations Environment Programme (UNEP) has performed a field survey at 11 sites located in Kosovo, where depleted uranium (DU) ammunitions were used by the North Atlantic Treaty Organization (NATO) during the last Balkans conflict (1999). Soil sampling was performed to assess the spread of DU ground contamination around and within the NATO target sites and the migration of DU along the soil profile. The 234U/238U and 235U/238U activity concentration ratios have been used as an indicator of natural against anthropogenic sources of uranium. The results show that levels of 238U activity concentrations in soils above 100 Bq x kg(-1) can be considered a 'tracer' of the presence of DU in soils. The results also indicate that detectable ground surface contamination by DU is limited to areas within a few metres from localised points of concentrated contamination caused by penetrator impacts. Vertical distribution of DU along the soil profile is measurable up to a depth of 10-20 cm. This latter aspect is of particular relevance for the potential risk of future contamination of groundwater.

  12. Thermal stress depletes energy reserves in Drosophila.

    PubMed

    Klepsatel, Peter; Gáliková, Martina; Xu, Yanjun; Kühnlein, Ronald P

    2016-09-19

    Understanding how environmental temperature affects metabolic and physiological functions is of crucial importance to assess the impacts of climate change on organisms. Here, we used different laboratory strains and a wild-caught population of the fruit fly Drosophila melanogaster to examine the effect of temperature on the body energy reserves of an ectothermic organism. We found that permanent ambient temperature elevation or transient thermal stress causes significant depletion of body fat stores. Surprisingly, transient thermal stress induces a lasting "memory effect" on body fat storage, which also reduces survivorship of the flies upon food deprivation later after stress exposure. Functional analyses revealed that an intact heat-shock response is essential to protect flies from temperature-dependent body fat decline. Moreover, we found that the temperature-dependent body fat reduction is caused at least in part by apoptosis of fat body cells, which might irreversibly compromise the fat storage capacity of the flies. Altogether, our results provide evidence that thermal stress has a significant negative impact on organismal energy reserves, which in turn might affect individual fitness.

  13. Preventing NAD+ Depletion Protects Neurons against Excitotoxicity

    PubMed Central

    Liu, Dong; Pitta, Michael; Mattson, Mark P.

    2008-01-01

    Neurons are excitable cells that require large amounts of energy to support their survival and functions and are therefore prone to excitotoxicity, which involves energy depletion. By examining bioenergetic changes induced by glutamate, we found that the cellular nicotinamide adenine dinucleotide (NAD+) level is a critical determinant of neuronal survival. The bioenergetic effects of mitochondrial uncoupling and caloric restriction were also examined in cultured neurons and rodent brain. 2, 4-dinitrophenol (DNP) is a chemical mitochondrial uncoupler that stimulates glucose uptake and oxygen consumption on cultured neurons, which accelerates oxidation of NAD(P)H to NAD+ in mitochondria. The NAD+-dependent histone deacetylase sirtulin 1 (SIRT1) and glucose transporter 1 (GLUT1) mRNA are upregulated mouse brain under caloric restriction. To examine whether NAD+ mediates neuroprotective effects, nicotinamide, a precursor of NAD+ and inhibitor of SIRT1 and poly (ADP-ribose) polymerase 1 (PARP1) (two NAD+-dependent enzymes), was employed. Nicotinamide attenuated excitotoxic death and preserved cellular NAD+ levels to support SIRT1 and PARP 1 activities. Our findings suggest that mild mitochondrial uncoupling and caloric restriction exert hormetic effects by stimulating bioenergetics in neurons thereby increasing tolerance of neurons to metabolic stress. PMID:19076449

  14. Recovery of Depleted Uranium Fragments from Soil

    SciTech Connect

    Farr, C.P.; Alecksen, T.J.; Heronimus, R.S.; Simonds, M.H.; Farrar, D.R.; Baker, K.R.; Miller, M.L.

    2008-07-01

    A cost-effective method was demonstrated for recovering depleted uranium (DU) fragments from soil. A compacted clean soil pad was prepared adjacent to a pile of soil containing DU fragments. Soil from the contaminated pile was placed on the pad in three-inch lifts using conventional construction equipment. Each lift was scanned with an automatic scanning system consisting of an array of radiation detectors coupled to a detector positioning system. The data were downloaded into ArcGIS for data presentation. Areas of the pad exhibiting scaler counts above the decision level were identified as likely locations of DU fragments. The coordinates of these locations were downloaded into a PDA that was wirelessly connected to the positioning system. The PDA guided technicians to the locations where hand-held trowels and shovels were used to remove the fragments. After DU removal, the affected areas were re-scanned and the new data patched into the data base to replace the original data. This new data set along with soil sample results served as final status survey data. (authors)

  15. Long term effects on the immune system following local radiation therapy for breast cancer. I. Cellular composition of the peripheral blood lymphocyte population

    SciTech Connect

    Rotstein, S.; Blomgren, H.; Petrini, B.; Wasserman, J.; Baral, E.

    1985-05-01

    Local radiation therapy for breast cancer depletes the blood of various subsets of lymphocytes. Previous studies showed that the recovery is still incomplete at 30 months. To further elucidate the recovery the authors examined blood lymphocyte counts of 138 disease-free women and various lymphocyte subsets in 102 of these patients. Total lymphocyte counts of the irradiated patients were still significantly reduced 10-11 years after treatment. This reduction was mainly attributable to a subnormal level of T-cells as determined by the monoclonal antibody Leu-1 and the ability to form rosettes with sheep erythrocytes, whereas the number of non-T cells, expressing C'3 receptors, did not differ significantly from the controls. Within the T-cell population a subset with helper/inducer phenotypes, detected by Leu-3a antibodies, was significantly reduced even 10-11 years after irradiation. The duration of the radiation induced reductions of different lymphocyte subsets may be related to the physiological turn-over of the cells or a changed distribution of cells in the body.

  16. Comparative cytotoxicity and genotoxicity of cobalt (II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro.

    PubMed

    Rajiv, S; Jerobin, J; Saranya, V; Nainawat, M; Sharma, A; Makwana, P; Gayathri, C; Bharath, L; Singh, M; Kumar, M; Mukherjee, A; Chandrasekaran, N

    2016-02-01

    Despite the extensive use of nanoparticles (NPs) in various fields, adequate knowledge of human health risk and potential toxicity is still lacking. The human lymphocytes play a major role in the immune system, and it can alter the antioxidant level when exposed to NPs. Identification of the hazardous NPs was done using in vitro toxicity tests and this study mainly focuses on the comparative in vitro cytotoxicity and genotoxicity of four different NPs including cobalt (II, III) oxide (Co3O4), iron (III) oxide (Fe2O3), silicon dioxide (SiO2), and aluminum oxide (Al2O3) on human lymphocytes. The Co3O4 NPs showed decrease in cellular viability and increase in cell membrane damage followed by Fe2O3, SiO2, and Al2O3 NPs in a dose-dependent manner after 24 h of exposure to human lymphocytes. The oxidative stress was evidenced in human lymphocytes by the induction of reactive oxygen species, lipid peroxidation, and depletion of catalase, reduced glutathione, and superoxide dismutase. The Al2O3 NPs showed the least DNA damage when compared with all the other NPs. Chromosomal aberration was observed at 100 µg/ml when exposed to Co3O4 NPs and Fe2O3 NPs. The alteration in the level of antioxidant caused DNA damage and chromosomal aberration in human lymphocytes.

  17. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    ClinicalTrials.gov

    2016-08-01

    Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

  18. Podocyte Depletion in Thin GBM and Alport Syndrome

    PubMed Central

    Wang, Su Q.; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C.

    2016-01-01

    The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2–17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman’s capsule) were present at 30–50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS. PMID:27192434

  19. Podocyte Depletion in Thin GBM and Alport Syndrome.

    PubMed

    Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

    2016-01-01

    The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman's capsule) were present at 30-50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

  20. Transient Treg depletion enhances therapeutic anti‐cancer vaccination

    PubMed Central

    Aston, Wayne J.; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L.; Solin, Jessica N.; Ma, Shaokang; Lesterhuis, W. Joost; Dick, Ian; Holt, Robert A.; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A.

    2016-01-01

    Abstract Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination. Conclusions BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies. PMID:28250921

  1. Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells.

    PubMed Central

    Staats, H F; Oakes, J E; Lausch, R N

    1991-01-01

    Passive transfer of a monoclonal antibody (MAb) specific for glycoprotein D (gD) is highly effective in preventing the development of herpes simplex virus type 1-induced stromal keratitis. In the present study, we investigated whether animals which had been functionally depleted of T-cell subsets or asialo GM1+ cells would continue to be responsive to MAb therapy. BALB/c mice were depleted of CD4+, CD8+, or asialo GM1+ cells by treatment with anti-L3T4, anti-Lyt 2.2, or anti-asialo GM1 antibodies, respectively. Functional depletion of CD4+ cells was documented by the loss of delayed-type hypersensitivity responsiveness, while CD8+ cell depletion was accompanied by abrogation of cytotoxic lymphocyte activity. Anti-asialo GM1 treatment led to the loss of natural killer cell lytic activity. Mice depleted of the desired cell population and infected on the scarified cornea with herpes simplex virus type 1 uniformly developed necrotizing stromal keratitis by 3 weeks postinfection. A single inoculation of anti-gD MAb (55 micrograms) given intraperitoneally 24 h postinfection strongly protected hosts depleted of CD4+ cells against stromal keratitis. Likewise, antibody treatment in CD8+ or asialo GM1+ cell-depleted hosts was as therapeutically effective as that seen in non-cell-depleted mice. We also observed that in cell-depleted mice, the virus spread into the central nervous system and caused encephalitis. The CD4+ cell-depleted mice were the most severely affected, as 100% developed fatal disease. Anti-gD MAb treatment successfully protected all (32 of 32) CD4+-, CD8+-, or asialo GM1(+)-depleted hosts against encephalitis. We therefore conclude that antibody-mediated prevention of stromal keratitis and encephalitis does not require the obligatory participation of CD4+, CD8+, or asialo GM1+ cells. However, when mice were simultaneously depleted of both CD4+ and CD8+ T-cell subsets, antibody treatment could not prevent fatal encephalitis. Thus, antibody can compensate for

  2. Lipopolysaccharide induces apoptosis in Carassius auratus lymphocytes, a possible role in pathogenesis of bacterial infection in fish.

    PubMed

    Xiang, Li-Xin; Peng, Bo; Dong, Wei-Ren; Yang, Zai-Feng; Shao, Jian-Zhong

    2008-01-01

    Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, is capable of eliciting a wide variety of pathophysiological effects, including endotoxin shock, tissue injury and lethality in both humans and animals. It is also a potent stimulant to initiate the proliferation, differentiation and activation of B lymphocytes and macrophages, resulting in changes of inflammatory cytokines, such as TNF-alpha, IL1-beta, IL6, IL-8 and IL-12, and enhancement of immune responses. However, little is known about its effect on the induction of apoptosis in lymphocytes. In the present study, the lymphocytes from Carassius auratus were employed for this purpose. The cells were exposed to LPS at various doses for different time periods. By careful apoptotic characteristic analysis, such as condensation of nuclear chromatin, fragmentation of genomic DNA and formation of apoptotic bodies, it provided the first evidence that LPS had apoptotic-inducing effect on fish lymphocytes in a time- and dose-dependent manner. LPS exposure induced significant increase of intracellular reactive oxygen species (ROS), loss of mitochondrial transmembrane potential (DeltaPsi), depletion of ATP production, down-regulation of Bcl-2 expression, up-regulation of Bax and mitochondrial NO-synthase (mNOS) expression, and selective activation of caspase-9 rather than caspase-8. Each of these observations suggests that the LPS-induced apoptosis in C. auratus lymphocytes occurs largely via the mitochondrial apoptotic pathway. This observation was different from the mechanism behind the LPS-induced apoptosis in mammalian macrophages/thymocytes that occurs via the TNF-alpha-mediated death-receptor pathway. Our study suggested the existence of a possible novel role in the pathogenesis of Gram-negative bacterial infection in fish and even in mammals, which may contribute to the therapy of bacterial diseases. Also, it will help to gain more insights into the mechanisms of septic shock and of LPS

  3. Differentiation Capacity of Cultured B Lymphocytes from Immunodeficient Patients

    PubMed Central

    Wu, L. Y. F.; Lawton, A. R.; Cooper, M. D.

    1973-01-01

    Peripheral blood lymphocytes from 27 healthy individuals and from 18 patients with a diverse spectrum of defects in humoral immunity were examined for their capacity to undergo terminal differentiation in vitro. Pokeweed mitogen induced cells from normal persons to synthesize and secrete IgM. IgG, and IgA as detected by Immunofluorescence and incorporation of [14C]amino acids, Lymphocytes from three boys with X-linked agammaglobulinemia were stimulated to proliferate, but did not synthesize immunoglobulin. Lymphocyte cultures from three of four patients having agammaglobulinemia with B lymphocytes produced different immunoglobulin classes in ratios similar to the in vivo distribution of classes of B lymphocytes, Lymphocytes from a dysgammaglobulinemic boy deficient in serum IgG and IgA, but who had normal numbers of IgM-, IgG-, and IgA-bearing B lymphocytes, could not be stimulated by pokeweed mitogen to make IgG and IgA. Synthesis and secretion of IgA, as well as IgM and IgG, was detected in cell cultures from each of 10 patients with isolated IgA deficiency. The results suggest that deficiencies in immunoglobulin synthesis may reflect either (a) failure to develop B lymphocytes, (b) arrested development of B lymphocytes due to intrinsic metabolic abnormalities, or (c) disturbance of factors extrinsic to the B lymphocyte which are essential for normal induction of plasma cell maturation. Images PMID:4543023

  4. Novel biphasic role for lymphocytes revealed during resolving inflammation

    PubMed Central

    Rajakariar, Ravindra; Lawrence, Toby; Bystrom, Jonas; Hilliard, Mark; Colville-Nash, Paul; Bellingan, Geoff; Fitzgerald, Desmond; Yaqoob, Muhammad M.

    2008-01-01

    Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection. PMID:18218853

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

    SciTech Connect

    Peters, B.A.; Sothmann, M.; Wehrenberg, W.B. )

    1989-01-01

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

  6. Heterogeneity of human lymphocyte Fc receptors. II. Relationship to antibody-dependent, cell-mediated cytotoxicity

    PubMed Central

    Gormus, B. J.; Woodson, Mildred; Kaplan, M. E.

    1978-01-01

    Human peripheral blood lymphocytes (PBL) were incubated (stripped) with pronase or papain and compared with unstripped lymphocytes for their ability to mediate antibody-dependent, cell-mediated cytotoxicity (ADCC). Despite marked removal or inactivation of receptors for heat-aggregated IgG (aggG) by proteolytic digestion, and pronounced changes in the percentages of cells rosetting with IgG-sensitized erythrocytes (EA) (decreased by papain, increased by pronase), stripped PBL functioned normally in ADCC. Stripped and unstripped lymphocytes were pre-treated with aggG to determine the role of aggG receptors in ADCC. AggG almost totally abolished ADCC by unstripped PBL, but inhibited ADCC by enzyme-stripped lymphocytes relatively poorly. Neither untreated nor stripped PBL were able to induce cytotoxicity of chicken erythrocyte (CRBC) target cells sensitized with the Fab'2 fragment of anti-CRBC IgG antibody (CRBC-A). Exposure of PBL to EA monolayers composed of CRBC-A or of sheep erythrocytes (SRBC) sensitized with rabbit anti-SRBC IgG antibody (SRBC-A) depleted PBL of cells that rosetted with CRBC-A and with human Rh-positive, type O erythrocytes sensitized with the human anti-Rh serum Ripley (HRBC-A Ripley). Non-adherent cells were incapable of binding aggG and had markedly diminished cytotoxicity in ADCC. Similarly, exposure of PBL to HRBC-A Ripley monolayers resulted in non-adherent cells that were incapable of rosette formation with HRBC-A or CRBC-A, failed to bind aggG, and exhibited significantly diminished ADCC activity. These studies indicated that: (1) cytotoxic effector PBL active in ADCC (K cells) have receptors for aggG and for EA; (2) PBL deficient in functional aggG receptors (enzymatically inactivated or removed) are capable of inducing normal levels of ADCC; (3) aggG and EA receptors appear to be closely associated on native K-cell membranes; (4) there is no clear-cut relationship in a given lymphocyte population between the presence of either aggG or

  7. A minor role of CD4+ T lymphocytes in the control of a primary infection of cattle with Mycoplasma mycoides subsp. mycoides

    PubMed Central

    2011-01-01

    Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides, is an important livestock disease in Africa. The current control measures rely on a vaccine with limited efficacy and occasional severe side effects. Knowledge of the protective arms of immunity involved in this disease will be beneficial for the development of an improved vaccine. In previous studies on cattle infected with M. mycoides subsp. mycoides, a correlation was detected between the levels of mycoplasma-specific IFN-γ-secreting CD4+ T lymphocytes and reduced clinical signs. However, no cause and effect has been established, and the role of such cells and of protective responses acquired during a primary infection is not known. We investigated the role of CD4+ T lymphocytes in CBPP by comparing disease patterns and post mortem findings between CD4+ T cell depleted and non-depleted cattle. The depletion was carried out using several injections of BoCD4 specific murine monoclonal antibody on day 6 after experimental endotracheal infection with the strain Afadé. All cattle were monitored clinically daily and sacrificed 28-30 days post-infection. Statistically significant but small differences were observed in the mortality rate between the depleted and non-depleted animals. However, no differences in clinical parameters (fever, signs of respiratory distress) and pathological lesions were observed, despite elimination of CD4+ T cells for more than a week. The slightly higher mortality in the depleted group suggests a minor role of CD4+ T cells in control of CBPP. PMID:21663697

  8. In vitro susceptibilities in lymphocytes from mothers and cord blood to the monofunctional alkylating agent EMS.

    PubMed

    Wyatt, N P; Falque-Gonzalez, C; Farrar, D; Tuffnell, D; Whitelaw, D; Knudsen, L E; Anderson, D

    2007-03-01

    It has been reported that children may experience different levels of chemical exposures than adults and that their sensitivities to chemical toxins may be increased or decreased when compared to adults. The perinatal period is one period in which these susceptibilities may be examined. Midwives at the Bradford Royal Infirmary collected venous blood samples from mothers at the time of birth and venous cord blood post-delivery. Lymphocytes were isolated from both blood types and examined in the alkaline comet assay using the monofunctional alkylating agent ethyl methanesulphonate (EMS). There were no biologically significant differences when subjects were categorized into subgroups based on lifestyle habits and physical characteristics, and overall there were no statistically significant differences in levels of DNA damage in mothers (n=22) and babies (n=22), except at the basal level (P<0.05), but mean values in babies were always lower over the EMS dose range. Whole blood was used in the micronucleus (MN) assay, and there was a significantly (P<0.05) higher rate of MN in mothers (n=17), per 1000 binucleates, as compared with lymphocytes from their offspring (n=17) at the basal level. This may be accounted for by age and endogenous factors. Overall, this current study cannot provide statistically significant evidence that children have either increased or decreased levels of susceptibility to a chemical toxin in comparison to adults when EMS is examined in vitro.

  9. Lymphocyte stimulation response in horses against phytohaemagglutinin and M protein of Streptococcus equi using whole blood.

    PubMed Central

    Srivastava, S K; Barnum, D A

    1982-01-01

    Lymphocyte stimulation was observed in whole equine blood in the presence of phytohaemagglutinin and M protein extracted from a typical strain of Streptococcus equi. Blood samples were collected from several healthy horses and horse and pony foals and cultured in vitro with varying concentrations of phytohaemagglutinin and M protein for several days. Phytohaemagglutinin was found to induce lymphocyte stimulation in these animals. Highest mean stimulation indices in horse foals (49.3 +/- 24.4) and pony foals (54.7 +/- 32.0) were observed with 0.625 and 1.25 micrograms/mL phytohaemagglutinin, respectively, at either 72 or 96 hours of incubation. Significantly higher radioactive counts per minute in horse and pony foals were recorded in blood cultures incubated with 0.625 and 1.25 micrograms/mL phytohaemagglutinin. M protein induced a dose related stimulation response in adult horses. Maximum stimulation indices were observed against 125 micrograms/mL M protein at 96 hours. These stimulation indices were higher in adult horses (40.0 +/- 2.2) than observed in pony foals (14.4 +/- 15.7). Higher stimulation levels in adult horses indicated either nonspecific stimulation against M protein or previous exposure of these animals to S. equi. PMID:7074416

  10. [Internal contamination with depleted uranium and health disorders].

    PubMed

    Pranjić, Nurka; Karamehić, Jasenko; Ljuca, Farid; Zigić, Zlata; Ascerić, Mensura

    2002-01-01

    In this review we used the published data on depleted uranium (experimental and epidemiological) from the current literature. Depleted uranium is a toxic heavy metal that in high dose may cause poisoning and health effects as those caused by lead, mercury, and chromium. It is slightly radioactive. The aim of this review was to select, to arrange, to present references of scientific papers, and to summarise the data in order to give a comprehensive image of the results of toxicological studies on depleted uranium that have been done on animals (including carcinogenic activity). We have also used epidemiological posted study results related to occupational and environmental exposure to depleted uranium. The toxicity of uranium has been studied extensively. The results of the studies indicated primarily its chemical toxicity, particularly renal effects, but depleted uranium is not radiological hazard. Uranium is not metal determined to be carcinogenic (the International Agency of Research on Cancer). The military use of depleted uranium will give additional insight into the toxicology of depleted uranium. The present controversy over the radiological and chemical toxicity of depleted uranium used in the Gulf War requests further experimental and clinical investigations of its effects on the biosphere and human beings.

  11. Whistler waves guided by density depletion ducts in a magnetoplasma

    SciTech Connect

    Bakharev, P. V.; Zaboronkova, T. M.; Kudrin, A. V.; Krafft, C.

    2010-11-15

    The guided propagation of whistler waves along cylindrical density depletion ducts in a magneto-plasma is studied. It is shown that, under certain conditions, such ducts can support volume and surface eigenmodes. The dispersion properties and field structure of whistler modes guided by density depletion ducts are analyzed. The effect of collisional losses in the plasma on the properties of modes is discussed.

  12. Optimal Allocation of Sampling Effort in Depletion Surveys

    EPA Science Inventory

    We consider the problem of designing a depletion or removal survey as part of estimating animal abundance for populations with imperfect capture or detection rates. In a depletion survey, animals are captured from a given area, counted, and withheld from the population. This proc...

  13. 26 CFR 1.613-1 - Percentage depletion; general rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Percentage depletion; general rule. 1.613-1 Section 1.613-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion;...

  14. Cholesterol Depletion Alters Cardiomyocyte Subcellular Signaling and Increases Contractility

    PubMed Central

    McIntosh, Victoria J.; Abou Samra, Abdul B.; Mohammad, Ramzi M.; Lasley, Robert D.

    2016-01-01

    Membrane cholesterol levels play an important factor in regulating cell function. Sarcolemmal cholesterol is concentrated in lipid rafts and caveolae, which are flask-shaped invaginations of the plasma membrane. The scaffolding protein caveolin permits the enrichment of cholesterol in caveolae, and caveolin interactions with numerous proteins regulate their function. The purpose of this study was to determine whether acute reductions in cardiomyocyte cholesterol levels alter subcellular protein kinase activation, intracellular Ca2+ and contractility. Methods: Ventricular myocytes, isolated from adult Sprague Dawley rats, were treated with the cholesterol reducing agent methyl-β-cyclodextrin (MβCD, 5 mM, 1 hr, room temperature). Total cellular cholesterol levels, caveolin-3 localization, subcellular, ERK and p38 mitogen activated protein kinase (MAPK) signaling, contractility, and [Ca2+]i were assessed. Results: Treatment with MβCD reduced cholesterol levels by ~45 and shifted caveolin-3 from cytoskeleton and triton-insoluble fractions to the triton-soluble fraction, and increased ERK isoform phosphorylation in cytoskeletal, cytosolic, triton-soluble and triton-insoluble membrane fractions without altering their subcellular distributions. In contrast the primary effect of MβCD was on p38 subcellular distribution of p38α with little effect on p38 phosphorylation. Cholesterol depletion increased cardiomyocyte twitch amplitude and the rates of shortening and relaxation in conjunction with increased diastolic and systolic [Ca2+]i. Conclusions: These results indicate that acute reductions in membrane cholesterol levels differentially modulate basal cardiomyocyte subcellular MAPK signaling, as well as increasing [Ca2+]i and contractility. PMID:27441649

  15. Depletion of Appalachian coal reserves - how soon?

    USGS Publications Warehouse

    Milici, R.C.

    2000-01-01

    Much of the coal consumed in the US since the end of the last century has been produced from the Pennsylvanian strata of the Appalachian basin. Even though quantities mined in the past are less than they are today, this basin yielded from 70% to 80% of the nation's annual coal production from the end of the last century until the early 1970s. During the last 25 years, the proportion of the nation's coal that was produced annually from the Appalachian basin has declined markedly, and today it is only about 40% of the total. The amount of coal produced annually in the Appalachian basin, however, has been rising slowly over the last several decades, and has ranged generally from 400 to 500 million tons (Mt) per year. A large proportion of Appalachian historical production has come from relatively few counties in southwestern Pennsylvania, northern and southern West Virginia, eastern Kentucky, Virginia and Alabama. Many of these counties are decades past their years of peak production and several are almost depleted of economic deposits of coal. Because the current major consumer of Appalachian coal is the electric power industry, coal quality, especially sulfur content, has a great impact on its marketability. High-sulfur coal deposits in western Pennsylvania and Ohio are in low demand when compared with the lower sulfur coals of Virginia and southern West Virginia. Only five counties in the basin that have produced 500 Mt or more exhibit increasing rates of production at relatively high levels. Of these, six are in the central part of the basin and only one, Greene County, Pennsylvania, is in the northern part of the basin. Decline rate models, based on production decline rates and the decline rate of the estimated, 'potential' reserve, indicate that Appalachian basin annual coal production will be 200 Mt or less by the middle of the next century. Published by Elsevier Science B.V.Much of the coal consumed in the US since the end of the last century has been produced

  16. Effects of depleted uranium on oxidative stress, detoxification, and defence parameters of zebrafish Danio rerio.

    PubMed

    Gagnaire, Beatrice; Cavalie, Isabelle; Camilleri, Virginie; Adam-Guillermin, Christelle

    2013-01-01

    In this study, we investigated the effects of depleted uranium (DU), the by-product of nuclear enrichment of uranium, on several parameters related to oxidative stress, detoxification, and the defence system in the zebrafish Danio rerio. Several parameters were recorded: phenoloxidase-like (PO) activity, reactive oxygen species (ROS) production, and 7-ethoxyresrufin-O-deethylase (EROD) activity. Experiments were performed on adult and larvae D. rerio. Adult fish were exposed for 28 days at 20 μg U/L followed by a 27-day depuration period. Eggs of D. rerio were exposed for 4 days at 0, 20, 100, 250, 500, and 1,000 μg U/L. Results showed that DU increased ROS production both in adult and in larvae even at the low concentrations tested and even during the depuration period for adult D. rerio. DU also modified PO-like activity, both in the D. rerio adult and larvae experiments, but in a more transient manner. EROD activity was not modified by DU, but sex effects were shown. Results are discussed by way of comparison with other known effects of uranium in fish. Overall, these results show that the mechanisms of action of DU in fish tend to be similar to the ones existing for mammals. These results encourage the development and use of innate immune biomarkers to understand the effects of uranium and, more generally, radionuclides on the fish immune system.

  17. Ozone Depletion Potential of CH3Br

    NASA Technical Reports Server (NTRS)

    Sander, Stanley P.; Ko, Malcolm K. W.; Sze, Nien Dak; Scott, Courtney; Rodriquez, Jose M.; Weisenstein, Debra K.

    1998-01-01

    The ozone depletion potential (ODP) of methyl bromide (CH3Br) can be determined by combining the model-calculated bromine efficiency factor (BEF) for CH3Br and its atmospheric lifetime. This paper examines how changes in several key kinetic data affect BEF. The key reactions highlighted in this study include the reaction of BrO + H02, the absorption cross section of HOBr, the absorption cross section and the photolysis products of BrON02, and the heterogeneous conversion of BrON02 to HOBR and HN03 on aerosol particles. By combining the calculated BEF with the latest estimate of 0.7 year for the atmospheric lifetime of CH3Br, the likely value of ODP for CH3Br is 0.39. The model-calculated concentration of HBr (approximately 0.3 pptv) in the lower stratosphere is substantially smaller than the reported measured value of about I pptv. Recent publications suggested models can reproduce the measured value if one assumes a yield for HBr from the reaction of BrO + OH or from the reaction of BrO + H02. Although the DeAlore et al. evaluation concluded any substantial yield of HBr from BrO + HO2 is unlikely, for completeness, we calculate the effects of these assumed yields on BEF for CH3Br. Our calculations show that the effects are minimal: practically no impact for an assumed 1.3% yield of HBr from BrO + OH and 10% smaller for an assumed 0.6% yield from BrO + H02.

  18. Removal of depleted uranium from contaminated soils.

    PubMed

    Choy, Christine Chin; Korfiatis, George P; Meng, Xiaoguang

    2006-08-10

    Contamination of soil and water with depleted uranium (DU) has increased public health concerns due to the chemical toxicity of DU at elevated dosages. For this reason, there is great interest in developing methods for DU removal from contaminated sources. Two DU laden soils, taken from U.S. Army sites, were characterized for particle size distribution, total uranium concentration and removable uranium. Soil A was found to be a well graded sand containing a total of 3210 mg/kg DU (3.99 x 10(4) Bq/kg, where a Becquerel (Bq) is a unit of radiation). About 83% of the DU in the fines fraction (particle diameter <0.075 mm, total DU 7732 mg/kg (9.61 x 10(4) Bq/kg)) was associated with the carbonate, iron and manganese oxide and organic matter fractions of the material. Soil B was classified as a sandy silt with total DU of 1560 mg/kg (1.94 x 10(4) Bq/kg). The DU content in the fines fraction was 5171 mg/kg (6.43 x 10(4) Bq/kg). Sequential extraction of the Soil B fines fraction indicated that 64% of the DU was present either as soluble U(VI) minerals or as insoluble U(IV). Citric acid, sodium bicarbonate and hydrogen peroxide were used in batch experiments to extract DU from the fines fraction of both soils. Citric acid and sodium bicarbonate were relatively successful for Soil A (50-60% DU removal), but not for Soil B (20-35% DU removal). Hydrogen peroxide was found to significantly increase DU extraction from both soils, attaining removals up to 60-80%.

  19. Impact of ozone depletion on immune function

    SciTech Connect

    Jeevan, A.; Kripke, M.L. . Dept. of Immunology)

    1993-06-01

    Depletion of stratospheric ozone is expected to lead to an increase in the amount of UV-B radiation present in sunlight. In addition to its well known ability to cause skin cancer, UV-B radiation has been shown to alter the immune system. The immune system is the body's primary defense mechanism against infectious diseases and protects against the development of certain types of cancer. Any impairment of immune function may jeopardize health by increasing susceptibility to infectious diseases, increasing the severity of infections, or delaying recovery for infections. In addition, impaired immune function can increase the incidence of certain cancers, particularly cancers of the skin. Research carried out with laboratory animals over the past 15 years has demonstrated that exposure of the skin to UV-B radiation can suppress certain types of immune responses. These include rejection of UV-induced skin cancers and melanomas, contact allergy reactions to chemicals, delayed-type hypersensitivity responses to microbial and other antigens, and phagocytosis and elimination of certain bacteria from lymphoid tissues. Recent studies with mycobacterial infection of mice demonstrated that exposure to UV-B radiation decreased the delayed hypersensitivity response to mycobacterial antigens and increased the severity of infection. In humans, UV-B radiation has also been shown to impair the contact allergy response. These studies demonstrate that UV radiation can decrease immune responses in humans and laboratory and raise the possibility that increased exposure to UV-B radiation could adversely affect human health by increasing the incidence or severity of certain infectious diseases.

  20. Barium Depletion in Hollow Cathode Emitters

    NASA Technical Reports Server (NTRS)

    Polk, James E.; Capece, Angela M.; Mikellides, Ioannis G.; Katz, Ira

    2009-01-01

    The effect of tungsten erosion, transport and redeposition on the operation of dispenser hollow cathodes was investigated in detailed examinations of the discharge cathode inserts from an 8200 hour and a 30,352 hour ion engine wear test. Erosion and subsequent re-deposition of tungsten in the electron emission zone at the downstream end of the insert reduces the porosity of the tungsten matrix, preventing the ow of barium from the interior. This inhibits the interfacial reactions of the barium-calcium-aluminate impregnant with the tungsten in the pores. A numerical model of barium transport in the internal xenon discharge plasma shows that the barium required to reduce the work function in the emission zone can be supplied from upstream through the gas phase. Barium that flows out of the pores of the tungsten insert is rapidly ionized in the xenon discharge and pushed back to the emitter surface by the electric field and drag from the xenon ion flow. This barium ion flux is sufficient to maintain a barium surface coverage at the downstream end greater than 0.6, even if local barium production at that point is inhibited by tungsten deposits. The model also shows that the neutral barium pressure exceeds the equilibrium vapor pressure of the impregnant decomposition reaction over much of the insert length, so the reactions are suppressed. Only a small region upstream of the zone blocked by tungsten deposits is active and supplies the required barium. These results indicate that hollow cathode failure models based on barium depletion rates in vacuum dispenser cathodes are very conservative.