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Sample records for lymphocytes cd69 molecule

  1. Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease.

    Science.gov (United States)

    Vitales-Noyola, Marlen; Martínez-Martínez, Rita; Loyola-Rodríguez, Juan P; Baranda, Lourdes; Niño-Moreno, Perla; González-Amaro, Roberto

    2017-08-01

    Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69 + Treg lymphocytes in patients with chronic periodontal disease. Peripheral blood samples (n = 33) and gingival tissue (n = 9) were obtained from patients with chronic periodontal disease. Blood samples from 25 healthy individuals were also studied. Levels of CD69 + Treg lymphocytes in peripheral blood and gingival tissue were determined by six-color multiparametric flow cytometry, immunofluorescence, and immunohistochemistry. The immune regulatory function of CD69 + Treg cells was tested by an in vitro assay of inhibition of lymphocyte activation. Percentages of CD69 + Treg cells were significantly higher in the peripheral blood from patients with active periodontal disease compared to healthy controls, and these percentages inversely correlated with the periodontal attachment loss. Increased numbers of these Treg cells were detected in the gingival tissue from active PD patients compared to their peripheral blood. However, the suppressive function of CD69 + Treg cells was significantly diminished in patients with periodontal disease compared to healthy controls. Our data suggest that CD69 + Treg cells seem to be another important piece in the complex immunopathogenesis of periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Re-Evaluation of Binding Properties of Recombinant Lymphocyte Receptors NKR-P1A and CD69 to Chemically Synthesized Glycans and Peptides

    Czech Academy of Sciences Publication Activity Database

    Rozbeský, Daniel; Krejzová, Jana; Křenek, Karel; Prchal, J.; Hrabal, R.; Kožíšek, Milan; Weignerová, Lenka; Fiore, M.; Dumy, P.; Renaudet, O.; Křen, Vladimír

    2014-01-01

    Roč. 15, č. 1 (2014), s. 1271-1283 E-ISSN 1422-0067 R&D Projects: GA MŠk(CZ) LD13042 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : CD69 * NKR-P1A * NMR titration Subject RIV: CE - Biochemistry Impact factor: 2.862, year: 2014

  3. The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

    Directory of Open Access Journals (Sweden)

    Katarina Radulovic

    Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

  4. Monocyte and lymphocyte surface molecules in severe sepsis and non-septic critically ill Patients.

    Science.gov (United States)

    Jämsä, Joel; Syrjälä, Hannu; Huotari, Virva; Savolainen, Eeva-Riitta; Ala-Kokko, Tero

    2017-06-01

    The aim of the present study was to investigate whether expression of monocyte and lymphocyte surface molecules differs between patients with severe sepsis and non-septic patients treated in the intensive care unit (ICU). The expression of monocyte CD14, CD40, CD80 and HLA-DR, and lymphocyte CD69 were analyzed using quantitative flow cytometry on three consecutive days in 27 patients with severe sepsis and in 15 non-septic patients. Receiver operating characteristic analyses were performed and each corresponding area under the curve (AUC) was determined. The results showed that the expression levels of CD40 on monocytes and CD69 on CD4+ T cells and on natural killer (NK) cells were highest in patients with severe sepsis (p sepsis and positive blood culture compared with those with negative blood culture (p sepsis detection were 0.836 for CD40, 0.872 for CD69 on NK cells, and 0.795 for CD69 on CD4+ T cells. These findings suggest that monocyte CD40 and CD69 on NK cells and CD4+ T cells could prove useful for new approaches in the identification of severe sepsis in the ICU. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  5. Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Naoki Mori; Chie Ishikawa; Masachika Senba

    2011-01-01

    AIM: To investigate and elucidate the molecular mech-anism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection.METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononu-clear cells (PBMCs), and CD4+T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori -induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island ( cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa-tients with H. pylori -positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori -induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori -induced CD69 mRNA expression.CONCLUSION: The results suggest that H. pylori in-duces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori -induced gastritis.

  6. Type II membrane protein CD69 regulates the formation of resting T-helper memory.

    OpenAIRE

    Shinoda, K.; Tokoyoda, K.; Hanazawa, A.; Hayashizaki, K.; Zehentmeier, S.; Hosokawa, H.; Iwamura, C.; Koseki, H.; Tumes, D. J.; Radbruch, A.; Nakayama, T.

    2012-01-01

    Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiat...

  7. Type II membrane protein CD69 regulates the formation of resting T-helper memory.

    Science.gov (United States)

    Shinoda, Kenta; Tokoyoda, Koji; Hanazawa, Asami; Hayashizaki, Koji; Zehentmeier, Sandra; Hosokawa, Hiroyuki; Iwamura, Chiaki; Koseki, Haruhiko; Tumes, Damon J; Radbruch, Andreas; Nakayama, Toshinori

    2012-05-08

    Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.

  8. Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

    Science.gov (United States)

    Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

    2017-01-01

    P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

  9. Study of CD69 antigen expression and integrity of leukocyte cellular membrane in stored platelet concentrates following irradiation and treatment with Mirasol® PRT System.

    Science.gov (United States)

    Lachert, Elżbieta; Woźniak, Jolanta; Antoniewicz-Papis, Jolanta; Krzywdzińska, Agnieszka; Kubis, Jolanta; Mikołowska, Agata; Letowska, Magdalena

    2017-01-01

    Leukocytes in transfused blood components, particularly residual lymphocytes, have been shown to contribute to the occurrence of various adverse reactions. One of the most severe is transfusionassociated graft versus host disease (TA-GvHD) following transfusion of blood components contaminated with immunocompetent T lymphocytes. Irradiation is a routine method for protection against TA-GvHD. According to the literature, some pathogen reduction methods have also been proven effective for the inactivation of T lymphocytes, and so they may be considered as an alternative to irradiation. Comparison of CD69 antigen expression and the integrity of the leukocyte cellular membrane in stored platelet concentrates (PCs) following irradiation with the Gammacell 3000 Elan (Nordion Inc., Ottawa, Canada) and treatment with the Mirasol® Pathogen Reduction Technology (PRT) System (Terumo BCT, Lakewood, USA). The study included seven experiments. For each experiment we used 3 PCs, for Mirasol® PRT System treatment (M), for Gammacell 3000 Elan irradiation (R), and for the control (C). 7-amino-actinomycin D (7-AAD, Becton Dickinson, Franklin Lakes, USA) permeability was used to determine lymphocyte viability while CD69 antigen expression was the marker of lymphocyte activation. Analyses of 7-AAD and CD69 antigen expression were performed in a FACS Canto I flow cytometer (Becton Dickinson, USA). During 6 storage days, viable lymphocyte count decreased to 28% (p = 0.001) in the Mirasol® PRT System treated PCs and to 65% (p = 0.004) in the irradiated PCs. A statistically significant increase in CD69 expression in the irradiated PCs was observed; 1.3-fold on day 3 and 1.5-fold on day 6. In the Mirasol ® PRT System treated PCs, no statistically significant increase was observed. The in vitro results suggest that the Mirasol® PRT System is as effective as irradiation due to donor leukocyte inactivation capacity.

  10. Signaling lymphocytic activation molecules Slam and cancers: friends or foes?

    Science.gov (United States)

    Fouquet, Gregory; Marcq, Ingrid; Debuysscher, Véronique; Bayry, Jagadeesh; Rabbind Singh, Amrathlal; Bengrine, Abderrahmane; Nguyen-Khac, Eric; Naassila, Mickael; Bouhlal, Hicham

    2018-03-23

    Signaling Lymphocytic Activation Molecules (SLAM) family receptors are initially described in immune cells. These receptors recruit both activating and inhibitory SH2 domain containing proteins through their Immunoreceptor Tyrosine based Switch Motifs (ITSMs). Accumulating evidence suggest that the members of this family are intimately involved in different physiological and pathophysiological events such as regulation of immune responses and entry pathways of certain viruses. Recently, other functions of SLAM, principally in the pathophysiology of neoplastic transformations have also been deciphered. These new findings may prompt SLAM to be considered as new tumor markers, diagnostic tools or potential therapeutic targets for controlling the tumor progression. In this review, we summarize the major observations describing the implications and features of SLAM in oncology and discuss the therapeutic potential attributed to these molecules.

  11. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open...... open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p ... was associated with increased expression of the adhesion molecule CD11a/CD18 on lymphocytes, while the expression of activation molecules on lymphocytes was unchanged....

  12. Intraepithelial lymphocytes express junctional molecules in murine small intestine

    International Nuclear Information System (INIS)

    Inagaki-Ohara, Kyoko; Sawaguchi, Akira; Suganuma, Tatsuo; Matsuzaki, Goro; Nawa, Yukifumi

    2005-01-01

    Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), β-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. γδ IEL showed higher level of these expressions than αβ IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC

  13. Cooperation between subunits is essential for high-affinity binding of N-acetyl-D-hexosamines to dimeric soluble and dimeric cellular forms of human CD69

    Czech Academy of Sciences Publication Activity Database

    Kavan, Daniel; Kubíčková, M.; Bílý, J.; Vaněk, O.; Hofbauerová, Kateřina; Mrázek, H.; Rozbeský, Daniel; Bojarová, Pavla; Křen, Vladimír; Žídek, L.; Sklenář, V.; Bezouška, K.

    2010-01-01

    Roč. 49, č. 19 (2010), s. 4060-4067 ISSN 0006-2960 R&D Projects: GA MŠk 1M0505; GA ČR GA303/09/0477; GA ČR GD305/09/H008; GA ČR GP203/09/P024 Institutional research plan: CEZ:AV0Z50200510 Keywords : cd 69 * N-acetyl-D-hexosamines * lymphocyte Subject RIV: CE - Biochemistry Impact factor: 3.226, year: 2010

  14. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open...

  15. Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

    Science.gov (United States)

    Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

    2016-01-01

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

  16. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open-heart...... open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p open-heart as well as abdominal operations. Thus CPB...

  17. Low dose radiation induced protein and its effect on expression of CD25 molecule in lymphocytes

    International Nuclear Information System (INIS)

    Lu Duicai; Su Liaoyuan

    2001-01-01

    Objective: To find the substantial basis for effects of low dose radiation, on development, extraction, and the biogical activity of the low-dose radiation-induced proteins, and the effects of LDR induced proteins on CD25 molecule expression of human lymphocytes. Methods: 1. Healthy Kumning male mice exposed to radiation of 226 Ra γ-rays at 5, 10 and 15 cGy respectively. The mice were killed 2 hours after exposure, the spleen cells were broken with ultrasonic energy and then ultra-centrifugalized at low temperature (4 degree C). The LDR-induced proteins were obtained in the supernatant solution. Then the changes of CD25 molecule was measured by flow cytometry (FCM) with immunofluorescence technique, which was used to reflect the effect of LDR induced proteins on CD25 molecule expression of human lymphocytes. Results: LDR induced proteins were obtained from spleen cells in mice exposed to 5-15 cGy whole body radiation. Conclusion: The expression of CD25 molecule of lymphocytes was increased significantly after use of LDR induced proteins. LDR induced proteins can enhance expression of CD25 molecule of lymphocytes slightly

  18. Interleukin 1-induced down-regulation of antibody binding to CD4 molecules on human lymphocytes

    DEFF Research Database (Denmark)

    Tvede, N; Christensen, L D; Ødum, Niels

    1988-01-01

    Interleukin 1 (IL-1) is involved in the early activation of T lymphocytes. The CD4 antigen, described as a phenotypic marker of helper T cells, is also important in early T-cell activation by its ability to bind to MHC class II molecules on antigen-presenting cells, and to transmit positive (and...

  19. Changes in lymphocyte subpopulations and adhesion/activation molecules following endotoxemia and major surgery

    DEFF Research Database (Denmark)

    Toft, P; Hokland, Marianne; Hansen, Tom Giedsing

    1995-01-01

    Major surgery as well as endotoxin-induced sepsis is accompanied by lymphocytopenia in peripheral blood. The purpose of this study was to investigate the redistribution of lymphocyte subpopulations and adhesion/activation molecules on lymphocytes. Twenty-four rats were included in the investigation....... Eight rats received an intraperitoneal injection of E. coli endotoxin (2 mg kg-1), eight rats had a sham operation performed while eight rats received isotonic saline and served as a control group. Blood samples were obtained by making an incision in the tail before and 2 and 5 h after surgery...... or administration of endotoxin or saline. After isolation of lymphocytes by gradient centrifugation, flow-cytometric immunophenotyping was performed using CD2, CD3, CD4, CD8, CD11/CD18, CD20, CD44 and MHC II monoclonal antibodies. Endotoxemia and surgery were both accompanied by increased serum cortisol...

  20. Role of signaling lymphocytic activation molecule in T helper cell responses

    Directory of Open Access Journals (Sweden)

    Jan E. de Vries

    1998-01-01

    Full Text Available Signaling lymphocytic activation molecule (SLAM; CDw150 is a 70 kDa glycoprotein. Signaling lymphocytic activation molecule is constitutively expressed on memory T cells, CD56+ T cells, a subset of T cell receptor γδ+ cells, immature thymocytes and, at low levels, on a proportion of peripheral blood B cells. Signaling lymphocytic activation molecule is rapidly upregulated on all T and B cells after activation. Engagement of SLAM by F(ab’2 fragments of an anti-SLAM monoclonal antibody (mAb A12 enhances antigen-specific T cell proliferation. In addition, mAb A12 was directly mitogenic for T cell clones and activated T cells. T cell proliferation induced by mAb A12 is independent of interleukin (IL-2, IL-4, IL-12 and IL-15, but is cyclosporin A sensitive. Ligation of SLAM during antigen-specific T cell proliferation resulted in upregulation of interferon (IFN-γ production, even by allergen-specific T helper cell (Th 2 clones, whereas the levels of IL-4 and IL-5 production were only marginally affected. The mAb A12 was unable to induce IL-4 and IL-5 production by Th1 clones. Co-stimulation of skin-derived Der P1-specific Th2 cells from patients with atopic dermatitis via SLAM resulted in the generation of a population of IFN-γ-producing cells, thereby reverting their phenotype to a Th0 pattern. Signaling lymphocytic activation molecule is a high-affinity self ligand mediating homophilic cell interaction. In addition, soluble SLAM enhances both T and B cell proliferation. Collectively, these data indicate that SLAM molecules act both as receptors and ligands that are not only involved in T cell expansion but also drive the expanding T cells during immune responses into the Th0/Th1 pathway. This suggests that signaling through SLAM plays a role in directing Th0/Th1 development.

  1. Isolation and Purification of an Early Pregnancy Factor–Like Molecule from Culture Supernatants Obtained from Lymphocytes of Pregnant Women

    OpenAIRE

    Aranha, Clara; Natraj, Usha; Iyer, K. S.; Shahani, Savitri

    1998-01-01

    Purpose:Our purpose was to determine whether lymphocytes synthesize proteins during pregnancy, to observe whether one of the proteins synthesized has early pregnancy factor (EPF)–like activity and to isolate and purify this molecule from culture supernatants obtained from stimulated lymphocytes of pregnant women.

  2. Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule

    Directory of Open Access Journals (Sweden)

    Dehai Yu

    2017-06-01

    Full Text Available Background/Aims: Adult T-cell leukemia/lymphoma (ATL is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. Methods: We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP for the treatment of ATL. Results: We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. Conclusion: The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL.

  3. Cell Adhesion Molecule and Lymphocyte Activation Marker Expression during Experimental Vaginal Candidiasis

    Science.gov (United States)

    Wormley, Floyd L.; Chaiban, Joseph; Fidel, Paul L.

    2001-01-01

    Cell-mediated immunity by Th1-type CD4+ T cells is the predominant host defense mechanism against mucosal candidiasis. However, studies using an estrogen-dependent murine model of vaginal candidiasis have demonstrated little to no change in resident vaginal T cells during infection and no systemic T-cell infiltration despite the presence of Candida-specific systemic Th1-type responses in infected mice. The present study was designed to further investigate these observations by characterizing T-cell activation and cell adhesion molecule expression during primary and secondary C. albicans vaginal infections. While flow cytometry analysis of activation markers showed some evidence for activation of CD3+ draining lymph node and/or vaginal lymphocytes during both primary and secondary vaginal Candida infection, CD3+ cells expressing the homing receptors and integrins α4β7, αM290β7, and α4β1 in draining lymph nodes of mice with primary and secondary infections were reduced compared to results for uninfected mice. At the local level, few vaginal lymphocytes expressed integrins, with only minor changes observed during both primary and secondary infections. On the other hand, immunohistochemical analysis of vaginal cell adhesion molecule expression showed increases in mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression during both primary and secondary infections. Altogether, these data suggest that although the vaginal tissue is permissive to cellular infiltration during a vaginal Candida infection, the reduced numbers of systemic cells expressing the reciprocal cellular adhesion molecules may preempt cellular infiltration, thereby limiting Candida-specific T-cell responses against infection. PMID:11447188

  4. Effect of low dose irradiation on expression of membrane molecules of T lymphocytes in cord blood

    International Nuclear Information System (INIS)

    Liu Chang'an; Yang Guang; Jia Tingzhen

    2001-01-01

    The membrane molecules expression of T lymphocytes of cord blood after low dose irradiation (LDI) was investigated. Freshly isolated lymphocytes from cord blood were irradiated with 62 mGy γ-ray. At different time (4 h, 12 h, 24 h) after irradiation the changes of TCR + , CD3 + , CD4 + , CD8 + cells were examined by flow cytometry with direct immunofluorescence, respectively. The experimental results showed that the proportion of CD3 + , TCR + /CD3 + , CD4 + , CD8 + cells increased significantly after LDI, with the most obvious enhancement noted in the 24 h experimental group. The ratio of CD4 to CD8 showed no significant changes. It is suggested that expedition of the maturation, activation and signal transduction of T lymphocytes from cord blood can be induced by irradiation of 62 mGy γ-ray. So the reconstruction of immune functions after cord blood transplantation can be accelerated, enhancing the graft versus leukemia (GVL) effect and preventing the tumor from relapsing

  5. Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

    Directory of Open Access Journals (Sweden)

    Antas Paulo RZ

    2002-01-01

    Full Text Available The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05 on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease.

  6. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

    Science.gov (United States)

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  7. Activated umbilical cord blood cells from pre-term and term neonates express CD69 and synthesize IL-2 but are unable to produce IFN-gamma.

    Science.gov (United States)

    Cérbulo-Vázquez, Arturo; Valdés-Ramos, Roxana; Santos-Argumedo, Leopoldo

    2003-01-01

    The immune response exhibits quantitative and qualitative differences throughout human development. Both phenotypical and functional immaturity of newborn immune cellular components have been reported. We aimed to analyze possible differences in cellular activation assessed by expression of surface CD69 and cytokine production in mononuclear peripheral blood cells from premature (term (>37 weeks of gestation) neonates compared to adult donors. Ten persons from each group were selected; none was infected, immunodepressed, under medical treatment, or had any congenital abnormalities. Blood was obtained from umbilical cord of term and pre-term donors and vein punction of adults. All samples were collected in heparin and subsequently activated with PHA-L or PMA plus ionomycin at 37 degrees C for 4 h. After incubation, cells were labeled to determine CD69 expression on CD3+CD4+, CD3+CD8+, CD19+, and CD16+56+ subpopulations. Intracellular staining was performed to analyze IFN-gamma, IL-2, and CD69 in CD3+ cells. After staining, cells were analyzed by flow cytometry. We first found a substantially higher number of CD3+CD4+CD69+ cells in premature and term neonates than in adults. Secondly, percentage of CD3+CD8+, CD56+, and CD19+ cells expressing CD69 was similar among the three groups. Thirdly, expression of CD69 was higher in CD19+ cells than in CD16+56+ cells of all three groups. Regarding cytokine production, IFN-gamma was detected only in cells from adults and was consistent in all individuals analyzed. In sharp contrast, IL-2 and intracellular CD69 (iCD69) were detected in all three groups, with no significant differences among them. Induction of IL-2 and iCD69 showed that lack of response with IFN-gamma was restricted to pre-term and newborn populations. In summary, our results showed that a) CD69 is an early activation marker of both mononuclear umbilical cord and peripheral blood cells activated by a mitogenic stimulus, and b) newborn CD3+ cells probably lack

  8. Detection of proliferating cell nuclear antigens and interleukin-2 beta receptor molecules on mitogen- and antigen-stimulated lymphocytes.

    Science.gov (United States)

    Hesketh, J; Dobbelaere, D; Griffin, J F; Buchan, G

    1993-01-01

    The expression of interleukin-2 receptors (IL-2R) and proliferating cell nuclear antigens (PCNA) were compared for their usefulness as markers of lymphocyte activation. Heterologous polyclonal (anti-bovine IL-2R) and monoclonal (anti-human PCNA) antibodies were used to detect the expression of these molecules on activated deer lymphocytes. Both molecules were co-expressed on blast cells which had been activated with mitogen [concanavalin A (Con A)]. There was detectable up-regulation of IL-2R expression in response to antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] stimulation while PCNA expression mimicked lymphocyte transformation (LT) reactivity. PCNA expression was found to more accurately reflect both antigen- and mitogen-activated lymphocyte activation, as estimated by LT activity. The expression of PCNA was used to identify antigen reactive cells from animals exposed to M. bovis. A very low percentage (1.1 +/- 0.4%) of peripheral blood lymphocytes from non-infected animals could be stimulated to express PCNA by in vitro culture with antigen (PPD). Within the infected group both diseased and healthy, 'in-contact', animals expressed significantly higher levels of PCNA upon antigen stimulation. PMID:8104884

  9. Non-traditional CD4+CD25-CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zhao, Xiao-su; Wang, Xu-hua; Zhao, Xiang-yu; Chang, Ying-jun; Xu, Lan-ping; Zhang, Xiao-hui; Huang, Xiao-jun

    2014-07-01

    Non-traditional CD4+CD25-CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT). The frequency of CD4+CD25-CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-β, IL-2 and IL-10) secretion. The results showed that the frequency of CD4+CD25-CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25-CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (>7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion. This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.

  10. Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69

    Czech Academy of Sciences Publication Activity Database

    Catelani, G.; D’Andrea, F.; Griselli, A.; Guazelli, L.; Němcová, P.; Bezouška, K.; Křenek, Karel; Křen, Vladimír

    2010-01-01

    Roč. 20, č. 15 (2010), s. 4645-4648 ISSN 0960-894X R&D Projects: GA MŠk OC 136; GA MŠk(CZ) LC06010 Institutional research plan: CEZ:AV0Z50200510 Keywords : Deoxynojirimycin * NK cells * hCD69 receptors Subject RIV: CC - Organic Chemistry Impact factor: 2.661, year: 2010

  11. Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

    Science.gov (United States)

    Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

    2018-06-01

    Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  12. Characterization of a novel human scavenger receptor cysteine-rich molecule SCART1 expressed by lymphocytes

    DEFF Research Database (Denmark)

    Holm, D.; Fink, D. R.; Steffensen, M. A.

    2013-01-01

    a member of the SRCR superfamily, mSCART1, which primarily is expressed on a large subset of γδ T cells in mice. Here we report the cloning and characterization of human SCART1 (hSCART1) mainly expressed by CD4(+) and CD8(+) T lymphocytes. The hSCART1 gene maps to chromosome 10, region q26.3, a region...... domain. Shorter splice forms have also been isolated. Quantitative real-time PCR analysis on human blood-fractions has shown that hSCART1 is expressed primarily by CD4(+) and CD8(+) T lymphocytes with either αβ or γδ T cell receptors, and real-time PCR on 22 different human tissues showed high expression...... that the protein plays a role in the immune system, perhaps as a co-receptor on αβ and γδ T cells....

  13. Ligation of MHC class I molecules on peripheral blood T lymphocytes induces new phenotypes and functions

    DEFF Research Database (Denmark)

    Bregenholt, S; Röpke, M; Skov, S

    1996-01-01

    of T cell-mediated cytotoxicity. Immediately following MHC-I ligation, the T cells responded with increased protein tyrosine phosphorylation, with new bands appearing in the SDS-PAGE. Exposure of T cells to immobilized anti-MHC-I Ab for 24 h induced an increased surface expression of the TCR/CD3 and CD......28 molecules. MHC-I-induced proliferation of purified T cells was dependent on cellular interactions with non-T cells. Under certain conditions, in which MHC-I was ligated by picogram concentrations of immobilized anti-MHC-I Ab, anti-TCR/CD3 Ab-induced proliferation of T cells was strongly inhibited....... These data clearly demonstrate that ligation of the MHC-I complex on T cells may induce both positive and negative signals. Since the physiologic ligands for MHC-I molecules are TCR and the CD8 molecules, our data may suggest that MHC-I molecules are instrumental in cellular interactions between T cells....

  14. CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Deaglio, Silvia; Capobianco, Andrea; Bergui, Luciana; Dürig, Jan; Morabito, Fortunato; Dührsen, Ulrich; Malavasi, Fabio

    2003-09-15

    The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CLL cells. Indeed, mAb ligation is followed by Ca2+ fluxes and by a markedly increased proliferation. The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell-receptor (BCR) complex and CD19. On mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a colocalization with the GM1 ganglioside and with CD81, a raft-resident protein. Finally, CD38 signaling in IL-2-treated B-CLL cells prolonged survival and induced the appearance of plasmablasts, providing a pathogenetic hypothesis for the occurrence of Richter syndrome.

  15. The Next Generation of Targeted Molecules for the Treatment of Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Jeyakumar, Deepa; O'Brien, Susan

    2016-11-15

    With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy. As a class of medications, B-cell receptor inhibitors have some unique side effects, including redistribution lymphocytosis. Toxicities associated specifically with ibrutinib include increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities: transaminitis, colitis, and pneumonitis. Targeted therapies recently approved for use in CLL include the novel anti-CD20 monoclonal antibodies obinutuzumab and ofatumumab, and the B-cell lymphoma 2 inhibitor venetoclax. This article describes the clinical data that led to approval of these B-cell receptor inhibitors for the treatment of CLL, and highlights newer agents in clinical development that target the same kinases as the currently available therapies.

  16. PKCθ is required for the activation of human T lymphocytes induced by CD43 engagement

    International Nuclear Information System (INIS)

    Rio, Roxana del; Rincon, Mercedes; Layseca-Espinosa, Esther; Fierro, Nora A.; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

    2004-01-01

    The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (α/β), nPKC (ε and θ), aPKC (ζ) and PKCμ. We also show that activation of PKCθ resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-κB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCθ plays a critical role in the co-stimulatory functions of CD43 in human T cells

  17. Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

    Directory of Open Access Journals (Sweden)

    Caixia Gao

    2017-12-01

    Full Text Available Swine leukocyte antigen (SLA class I molecules play a crucial role in generating specific cellular immune responses against viruses and other intracellular pathogens. They mainly bind and present antigens of intracellular origin to circulating MHC I-restricted cytotoxic T lymphocytes (CTLs. Binding of an appropriate epitope to an SLA class I molecule is the single most selective event in antigen presentation and the first step in the killing of infected cells by CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA molecules. In this study, we constructed SLA class I complexes in vitro comprising viral epitope peptides, the extracellular region of the SLA-1 molecules, and β2-microglobulin (β2m using splicing overlap extension polymerase chain reaction (SOE-PCR. The protein complexes were induced and expressed in an Escherichia coli prokaryotic expression system and subsequently purified and refolded. Specific binding of seven SLA-1 proteins to one classical swine fever virus (CSFV and four porcine reproductive and respiratory syndrome virus (PRRSV epitope peptides was detected by enzyme-linked immunosorbent assay (ELISA-based method. The SLA-1∗13:01, SLA-1∗11:10, and SLA-1∗11:01:02 proteins were able to bind specifically to different CTL epitopes of CSFV and PRRSV and the MHC restrictions of the five epitopes were identified. The fixed combination of Asn151Val152 residues was identified as the potentially key amino acid residues influencing the binding of viral several CTL epitope peptides to SLA-1∗13:01 and SLA-1∗04:01:01 proteins. The more flexible pocket E in the SLA-1∗13:01 protein might have fewer steric limitations and therefore be able to accommodate more residues of viral CTL epitope peptides, and may thus play a critical biochemical role in determining the peptide-binding motif of SLA-1∗13:01. Characterization of the binding specificity of peptides to SLA class I molecules provides an

  18. Increased numbers of CD38 molecules on bright CD8+ T lymphocytes in infectious mononucleosis caused by Epstein–Barr virus infection

    Science.gov (United States)

    ŽIDOVEC LEPEJ, S; VINCE, A; ÐAKOVIĆ RODE, O; REMENAR, A; JEREN, T

    2003-01-01

    The aim of this study was to quantify the expression of CD38 on CD8+ T lymphocytes of patients with infectious mononucleosis (IM) caused by Epstein–Barr virus (EBV) and cytomegalovirus (CMV). CD38 quantification technique chosen for this study was based on the enumeration of CD38 antibody binding sites in comparison to the quantification standards rather than determining relative fluorescence, which is difficult to standardize. The study enrolled 19 patients with typical clinical and laboratory parameters compatible with EBV-induced IM as well as 10 patients with atypical clinical presentation of this disease. Furthermore, CD38 expression was analysed in a group of 13 patients with IM caused by CMV infection. CD38 quantification was performed within 6 days of the presentation of symptoms. All three groups of IM patients showed a statistically significant increase in the number of anti-CD38 antibody binding sites (which correspond to the number of CD38 molecules) on bright CD8+ T lymphocytes compared to healthy controls. The numbers of CD38 molecules expressed on CD8+ T lymphocytes did not differ significantly between IM patients with typical and atypical clinical presentation of the disease. Patients with CMV-induced IM had significantly lower numbers of CD38 molecules expressed on CD8+ T lymphocytes. Therefore, we conclude that CD38 quantification could be helpful in differential diagnostics of IM cases with atypical clinical presentation. PMID:12930365

  19. The pattern recognition molecule ficolin-1 exhibits differential binding to lymphocyte subsets, providing a novel link between innate and adaptive immunity

    DEFF Research Database (Denmark)

    Genster, Ninette; Ma, Ying Jie; Munthe-Fog, Lea

    2014-01-01

    is unknown. Recognition of healthy host cells by a pattern recognition molecule constitutes a potential hazard to self cells and tissues, emphasizing the importance of further elucidating the reported self-recognition. In the current study we investigated the potential recognition of lymphocytes by ficolin-1...... and demonstrated that CD56(dim) NK-cells and both CD4(+) and CD8(+) subsets of activated T-cells were recognized by ficolin-1. In contrast we did not detect binding of ficolin-1 to CD56(bright) NK-cells, NKT-cells, resting T-cells or B-cells. Furthermore, we showed that the protein-lymphocyte interaction occurred...

  20. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier.

    Science.gov (United States)

    Curis, Céline; Percher, Florent; Jeannin, Patricia; Montange, Thomas; Chevalier, Sébastien A; Seilhean, Danielle; Cartier, Luis; Couraud, Pierre-Olivier; Gout, Olivier; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel; Afonso, Philippe V

    2016-08-15

    Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1-infected lymphocytes, both in chronically infected cell lines and in primary infected CD4(+) T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-κB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear

  1. Immune Checkpoint Molecules on Tumor-Infiltrating Lymphocytes and Their Association with Tertiary Lymphoid Structures in Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Cinzia Solinas

    2017-10-01

    Full Text Available There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC, particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4+ or CD8+ T cells and CTLA-4 is expressed on CD4+ T cells. The global proportion of PD-L1+, PD-L2+, LAG3+, and TIM3+ tumor-infiltrating lymphocytes (TIL was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS. PD-L1+, PD-L2+, LAG3+, and TIM3+ cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity

  2. Recent host range expansion of canine distemper virus and variation in its receptor, the signaling lymphocyte activation molecule, in carnivores.

    Science.gov (United States)

    Ohishi, Kazue; Suzuki, Rintaro; Maeda, Taro; Tsuda, Miwako; Abe, Erika; Yoshida, Takao; Endo, Yasuyuki; Okamura, Maki; Nagamine, Takashi; Yamamoto, Hanae; Ueda, Miya; Maruyama, Tadashi

    2014-07-01

    The signaling lymphocyte activation molecule (SLAM) is a receptor for morbilliviruses. To understand the recent host range expansion of canine distemper virus (CDV) in carnivores, we determined the nucleotide sequences of SLAMs of various carnivores and generated three-dimensional homology SLAM models. Thirty-four amino acid residues were found for the candidates binding to CDV on the interface of the carnivore SLAMs. SLAM of the domestic dog (Canis lupus familiaris) were similar to those of other members of the suborder Caniformia, indicating that the animals in this group have similar sensitivity to dog CDV. However, they were different at nine positions from those of felids. Among the nine residues, four of domestic cat (Felis catus) SLAM (72, 76, 82, and 129) and three of lion (Panthera leo persica) SLAM (72, 82, and 129) were associated with charge alterations, suggesting that the felid interfaces have lower affinities to dog CDV. Only the residue at 76 was different between domestic cat and lion SLAM interfaces. The domestic cat SLAM had threonine at 76, whereas the lion SLAM had arginine, a positively charged residue like that of the dog SLAM. The cat SLAM with threonine is likely to have lower affinity to CDV-H and to confer higher resistance against dog CDV. Thus, the four residues (72, 76, 82, and 129) on carnivore SLAMs are important for the determination of affinity and sensitivity with CDV. Additionally, the CDV-H protein of felid strains had a substitution of histidine for tyrosine at 549 of dog CDV-H and may have higher affinity to lion SLAM. Three-dimensional model construction is a new risk assessment method of morbillivirus infectivity. Because the method is applicable to animals that have no information about virus infection, it is especially useful for morbillivirus risk assessment and wildlife conservation.

  3. Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Kyttaris, Vasileios C; Tsokos, George C

    2017-01-01

    Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported. We examined the expression of SLAMF1-7 on peripheral blood T cells, B cells, monocytes, and their respective differentiated subsets, in patients with SLE and healthy controls in a systematic manner. SLAMF1 levels were increased on both T cell and B cells and their differentiated subpopulations in patients with SLE. SLAMF2 was increased on SLE CD4+ and CD8+ T cells. The frequency of SLAMF4+ and SLAMF7+ central memory and effector memory CD8+ T cells was reduced in SLE patients. Naïve CD4+ and CD8+ SLE T cells showed a slight increase in SLAMF3 levels. No differences were seen in the expression of SLAMF5 and SLAMF6 among SLE patients and healthy controls. Overall, the expression of various SLAMF receptors is dysregulated in SLE and may contribute to the immunopathogenesis of the disease.

  4. Effect of the signaling lymphocytic activation molecule (SLAM in the modulation of T cells in immune response to Leishmania braziliensis in vitro

    Directory of Open Access Journals (Sweden)

    Zirlane Castelo Branco Coêlho

    2017-02-01

    Full Text Available Introduction: Signaling lymphocyte activation molecule (SLAM is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages, and DC. Studies have shown PBMC from healthy individuals exposed to Leishmania differ in IFN-γ production. Objective: We investigated the role of SLAM signaling pathway in PMBC from high (HP and low (LP IFN-γ producers exposed to L. braziliensis in vitro. Methods: PBMC from 43 healthy individuals were cultured with or without antigen, α-SLAM, rIL-12 and rIFN-γ. The cytokines production was evaluated by ELISA, and SLAM expression by flow cytometry. Results: L. braziliensis associated with rIFN-γ or rIL-12 reduced early SLAM but did not modify this response later in HP. α-SLAM did not alter CD3+SLAM+ expression, and not affected IFN-γ and IL-13 production, in both groups, but increased significantly IL-10 in HP. Leishmania associated with α-SLAM and rIL-12 increased IFN-γ in LP, as well as IL-13 in HP. LP group presented low IFN-γ and IL-13 production, and low SLAM expression. Conclusion: Collectively, these findings suggest that when PBMC from healthy individuals are sensitized with L. braziliensis in vitro, SLAM acts in modulating Th1 response in HP individuals and induces a condition of immunosuppression in LP individuals.

  5. The expression of CD25, CD11b, SWC1, SWC7, MHC-II, and family of CD45 molecules can be used to characterize different stages of gamma delta T lymphocytes in pigs

    Czech Academy of Sciences Publication Activity Database

    Štěpánová, Kateřina; Šinkora, Marek

    2012-01-01

    Roč. 36, č. 4 (2012), s. 728-740 ISSN 0145-305X R&D Projects: GA ČR GA524/07/0087 Institutional research plan: CEZ:AV0Z50200510 Keywords : Porcine immune system * Cell surface molecules * Lymphocyte subpopulations Subject RIV: EC - Immunology Impact factor: 3.238, year: 2012

  6. Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

    Science.gov (United States)

    Stratigou, Victoria; Doyle, Anne F; Carlucci, Francesco; Stephens, Lauren; Foschi, Valentina; Castelli, Marco; McKenna, Nicola; Cook, H Terence; Lightstone, Liz; Cairns, Thomas D; Pickering, Matthew C; Botto, Marina

    2017-07-01

    The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  7. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes

    NARCIS (Netherlands)

    Mackay, Laura K.; Minnich, Martina; Kragten, Natasja A. M.; Liao, Yang; Nota, Benjamin; Seillet, Cyril; Zaid, Ali; Man, Kevin; Preston, Simon; Freestone, David; Braun, Asolina; Wynne-Jones, Erica; Behr, Felix M.; Stark, Regina; Pellicci, Daniel G.; Godfrey, Dale I.; Belz, Gabrielle T.; Pellegrini, Marc; Gebhardt, Thomas; Busslinger, Meinrad; Shi, Wei; Carbone, Francis R.; van Lier, René A. W.; Kallies, Axel; van Gisbergen, Klaas P. J. M.

    2016-01-01

    Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific

  8. Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells.

    Science.gov (United States)

    Delneste, Y; Jeannin, P; Gosset, P; Lassalle, P; Cardot, E; Tillie-Leblond, I; Joseph, M; Pestel, J; Tonnel, A B

    1995-01-01

    Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site. PMID:7542574

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

    Science.gov (United States)

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

    2016-01-01

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

  10. [Activation of peripheral T lymphocytes in children with epilepsy and production of cytokines].

    Science.gov (United States)

    Yang, Jie; Hu, Chongkang; Jiang, Xun

    2016-09-01

    Objective To study the state of peripheral T lymphocytes and cytokine levels in children with epilepsy. Methods Twenty children with epilepsy and 20 healthy age-matched children were recruited and their peripheral blood was collected. The activation of T lymphocytes was evaluated by detecting the expressions of CD25, CD69 and cytotoxic T lymphocyte-assicated antigen 4 (CTLA4). The function of T lymphocytes was evaluated by detecting the expressions of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-17A and IL-6. The activation of regulatory T cells (Tregs) was evaluated by detecting the expression of IL-10. Results Children with epilepsy had higher expressions of CD25, CD69 and CTLA-4 in T lymphocytes than the controls did. The expressions of IFN-γ, TNF-α, IL-17A and IL-6 in T lymphocytes of children with epilepsy were higher than those of the controls. Frequency of Tregs producing IL-10 was higher in children with epilepsy as compared with the controls. Conclusion Peripheral T lymphocytes of children with epilepsy are activated and produce cytokines.

  11. The adaptor molecule signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is essential in mechanisms involving the Fyn tyrosine kinase for induction and progression of collagen-induced arthritis.

    Science.gov (United States)

    Zhong, Ming-Chao; Veillette, André

    2013-11-01

    Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.

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

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

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

  13. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  14. Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis.

    Science.gov (United States)

    Tsujimura, Shizuyo; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya

    2010-04-01

    P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.

  15. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Luciana Santos Cardoso

    2013-01-01

    Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

  16. Major histocompatibility complex class I molecule expression is normal on peripheral blood lymphocytes from patients with insulin-dependent diabetes mellitus.

    OpenAIRE

    Hao, W; Gladstone, P; Engardt, S; Greenbaum, C; Palmer, J P

    1996-01-01

    Recent work from one laboratory has shown, in both nonobese diabetic mice and humans, an association between insulin-dependent diabetes mellitus (IDDM) and quantitative difference in MHC class I molecule expression. This reported decrease in MHC class I molecule expression is very controversial in the nonobese diabetic mouse model of IDDM, but to our knowledge, it has not been evaluated by another group in human IDDM. To evaluate this question, we studied 30 patients with IDDM and 30 age- and...

  17. Niclosamide, an anti-helminthic molecule, downregulates the retroviral oncoprotein Tax and pro-survival Bcl-2 proteins in HTLV-1-transformed T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Di [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Yuan, Yunsheng [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai (China); Chen, Li [Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Liu, Xin; Belani, Chandra [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Cheng, Hua, E-mail: hcheng@ihv.umaryland.edu [Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-08-14

    Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide facilitated degradation of the Tax protein in proteasome. Consistent with niclosamide-mediated Tax degradation, this compound inhibited activities of MAPK/ERK1/2 and IκB kinases. In addition, niclosamide downregulated Stat3 and pro-survival Bcl-2 family members such as Mcl-1 and repressed the viral gene transcription of HTLV-1 through induction of Tax degradation. Since Tax, Stat3 and Mcl-1 are crucial molecules for promoting survival and growth of HTLV-1-transformed T cells, our findings demonstrate a novel mechanism of niclosamide in inducing Tax degradation and downregulating various cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia cells. - Highlights: • Niclosamide is a promising therapeutic candidate for adult T cell leukemia. • Niclosamide employs a novel mechanism through proteasomal degradation of Tax. • Niclosamide downregulates certain cellular pro-survival molecules.

  18. RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes.

    Science.gov (United States)

    Ganju, R K; Hatch, W C; Avraham, H; Ona, M A; Druker, B; Avraham, S; Groopman, J E

    1997-03-17

    The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.

  19. Autoimmune responses in patients with linear IgA bullous dermatosis: both autoantibodies and T lymphocytes recognize the NC16A domain of the BP180 molecule.

    Science.gov (United States)

    Lin, Mong-Shang; Fu, Chang-Ling; Olague-Marchan, Monica; Hacker, Mary K; Zillikens, Detlef; Giudice, George J; Fairley, Janet A

    2002-03-01

    Linear IgA bullous disease (LABD) is an autoimmune skin disease characterized by subepidermal blisters and IgA autoantibodies directed against the epidermal basement membrane zone (BMZ) of the skin. Various antigens have been identified as targets of IgA autoantibodies including BP180, a type II glycoprotein that spans the BMZ and lamina lucida. Previously, we have identified a subset of LABD patients whose sera contained IgA antibodies against the 16th noncollagenous (NC16A) domain of BP180. NC16A was previously shown to harbor epitopes that are recognized by both autoantibodies and T cells from patients with bullous pemphigoid and herpes gestationis and is thought to be associated with the development of these immunobullous diseases. The aim of this study was to determine whether T lymphocytes from LABD patients with anti-NC16A IgA autoantibodies respond to epitopes in the same region of the BP180 protein. Indeed, of the four LABD patients in our study, all had T cells that specifically proliferated in response to NC16A. Moreover, two subfragments of NC16A were identified as the predominant targets of LABD T cells. Further analysis of T cell lines and clones derived from these patients revealed that these cells express a CD4 memory T cell phenotype and secrete a Th1/Th2 mixed-cytokine profile, characteristics similar to those of T cells in bullous pemphigoid patients. Our data suggest that the BP180 protein, typically the NC16A region, is the common target of both cellular and humoral immune responses in some LABD patients. This information helps to further elucidate the autoimmune mechanisms in this disease.

  20. Specialities of the differentiation conditions for the memory cells - either initial or enriched secondary cytotoxic T lymphocyte precursors (pCTL-2) specific to the MHC molecule class 1

    International Nuclear Information System (INIS)

    Brondz, B.D.; Osipova, T.V.; Aptikaeva, G.F.; Kronin, V.V.

    1989-01-01

    The in vivo induced pCTL-2 with phenotype L3T4 - Lyt2 + , specific to the H-2K b molecule, turn into effector CTLs during 4 days in the mixed lymphocyte culture (with heat-treated donor stimulators) much more efficiency when donor and recipient are different from one another not only in MHC class 1 (anti-BIO, MBR BIO.AKM) but in 1+2 (K b +1 b ) anti-C57BL/6 BIAD2(R1O1). The initial pCTL-2 differentiation in enhanced as a result of synergistic effect between the K b alloantigen and rIL2. The anti-K b pCTL-2, being separated from helper T cells by means of absorption onto the macrophage donor monolayer and elution from it, give rise to pronounced differentiation in simplified conditions, irrespective of the stimulator presence and without external rIL2. It is supposed that these phenomena are roused to secrection of the CTL differentiation factor by the eluted pCTL-2 themselves, and besides, rIL2 may promote for secretion of this factor additionally

  1. Immunophenotypic profiles of peripheral blood lymphocytes on the day of embryo transfer in women undergoing in vitro fertilization.

    Directory of Open Access Journals (Sweden)

    Tomasz Baczkowski

    2008-04-01

    Full Text Available Evaluation of different types of lymphocyte subpopulations in the peripheral blood has unknown and controversial significance in diagnosis of infertility. The aim of the study was to evaluate selected blood lymphocytes in patients treated with intracytoplasmic sperm injection (ICSI.

    MATERIALS AND METHODS
    women were divided into three groups: (1 control fertile group (n=18, (2 infertile women that achieved (n=32, and (3 did not achieve a pregnancy after ICSI (n=26. The following types of leukocytes were analyzed by three-colour flow cytometry by detection of specific CD antigens: lymphocytes T (CD3+, B (CD19+ and CD5+CD19+, T and B (CD5+, NK cells (CD56+CD16-, CD56-CD16+, CD56+CD16+, CD56brightCD16-, CD56dimCD16+. Additionally, the antigen of early activation (CD69 was evaluated on T, B and NK cells. The results were presented as a percentage and total counts of all lymphocytes.

    RESULTS
    The percentage of total NK cells (CD56+CD16+, CD56+CD16- and CD56-CD16+ did not differ between pregnant and non pregnant women and was lower comparing to control group. Fractions of CD56-CD16+ cells were higher in pregnant vs. non-pregnant women. The percentages of CD56brightCD16- NK cells were higher in control group comparing to both ICSI treated groups. Other fractions of lymphocyte subpopulations, including activated cells (with CD69 expression did not differ between the analyzed groups. Total counts of CD56-CD16+ cells were higher in pregnant vs. non-pregnant group, and the CD56brightCD16- cells was more abundant in control group vs. women with unsuccessful ICSI.

    CONCLUSIONS
    Testing of peripheral blood NK cells and the others lymphocytes has limited value as a prognostic factor in ICSI treated patients. The antigen of early lymphocytic activation (CD69 has not any predictive value in prognosis of ICSI outcome.

  2. Development of an Immunoperoxidase Monolayer Assay for the Detection of Antibodies against Peste des Petits Ruminants Virus Based on BHK-21 Cell Line Stably Expressing the Goat Signaling Lymphocyte Activation Molecule.

    Directory of Open Access Journals (Sweden)

    Jialin Zhang

    Full Text Available From 2013 to 2015, peste des petits ruminants (PPR broke out in more than half of the provinces of China; thus, the application and development of diagnostic methods are very important for the control of PPR. Here, an immunoperoxidase monolayer assay (IPMA was developed to detect antibodies against PPR. However, during IPMA development, we found that Vero cells were not the appropriate choice because staining results were not easily observed. Therefore, we first established a baby hamster kidney-goat signaling lymphocyte activation molecule (BHK-SLAM cell line that could stably express goat SLAM for at least 20 generations. Compared with Vero cells, the PPR-mediated cytopathic effect occurred earlier in BHK-SLAM cells, and large syncytia appeared after virus infection. Based on this cell line and recombinant PPR virus expressing the green fluorescent protein (GFP (rPPRV-GFP, an IPMA for PPR diagnosis was developed. One hundred and ninety-eight PPR serum samples from goats or sheep were tested by the IPMA and virus neutralization test (VNT. Compared with the VNT, the sensitivity and specificity of the IPMA were 91% and 100%, respectively, and the coincidence rate of the two methods was 95.5%. The IPMA assay could be completed in 4 h, compared with more than 6 d for the VNT using rPPRV-GFP, and it is easily performed, as the staining results can be observed under a microscope. Additionally, unlike the VNT, the IPMA does not require antigen purification, which will reduce its cost. In conclusion, the established IPMA will be an alternative method that replaces the VNT for detecting antibodies against PPRV in the field.

  3. Measurement of exercise-induced oxidative stress in lymphocytes.

    Science.gov (United States)

    Turner, James E; Bosch, Jos A; Aldred, Sarah

    2011-10-01

    Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

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

    Directory of Open Access Journals (Sweden)

    Li-Xin Sun

    2014-01-01

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

  5. Chronic lymphocytic leukemia (CLL)

    Science.gov (United States)

    ... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

  6. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  7. Radiation effects on lymphocytes

    International Nuclear Information System (INIS)

    Roser, B.

    1976-01-01

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

  8. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

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

  9. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

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

    Directory of Open Access Journals (Sweden)

    Yao Wang

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

  11. Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice

    Directory of Open Access Journals (Sweden)

    Xue Luo

    2016-04-01

    Full Text Available Objectives: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs on the immune function of splenic lymphocytes in mice. Material and Methods: Twenty male Kunming mice (6 weeks old, weighing 18– 25 g, were randomly divided into sham exposure (N = 10 and 500 μT MFs (N = 10 groups. The mice in the MFs group were exposed to 500 μT MFs for 8 h daily (5 days/week for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69 in mouse prime splenic lymphocytes activated by para-Methoxyamphetamine (PMA and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640 and exposed to 0 μT, 250 μT, 500 μT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2 at 37°C for 6 h. The levels of interleukin-2 (IL-2, IL-4, interferon-gamma (IFN-γ, GATA binding protein 3 (GATA-3 and T cell-specific T-box transcription factor (T-bet were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR, respectively. The expression of CD69 was checked using the flow cytometry. Results: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. Conclusions: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic

  12. Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients.

    Science.gov (United States)

    Pino-Otín, M R; Viñas, O; de la Fuente, M A; Juan, M; Font, J; Torradeflot, M; Pallarés, L; Lozano, F; Alberola-Ila, J; Martorell, J

    1995-03-15

    CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation.

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

    Science.gov (United States)

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

    2017-03-01

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

  14. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    Full Text Available Human induced pluripotent stem cells (hiPSCs have enormous potential for the treatment of inherited and acquired disorders. Recently, antigen-specific T lymphocytes derived from hiPSCs have been reported. However, T lymphocyte populations with broad T cell receptor (TCR diversity have not been generated. We report that hiPSCs derived from skin biopsy are capable of producing T lymphocyte populations with a broad TCR repertoire. In vitro T cell differentiation follows a similar developmental program as observed in vivo, indicated by sequential expression of CD7, intracellular CD3 and surface CD3. The γδ TCR locus is rearranged first and is followed by rearrangement of the αβ locus. Both γδ and αβ T cells display a diverse TCR repertoire. Upon activation, the cells express CD25, CD69, cytokines (TNF-α, IFN-γ, IL-2 and cytolytic proteins (Perforin and Granzyme-B. These results suggest that most, if not all, mechanisms required to generate functional T cells with a broad TCR repertoire are intact in our in vitro differentiation protocol. These data provide a foundation for production of patient-specific T cells for the treatment of acquired or inherited immune disorders and for cancer immunotherapy.

  15. Co-Culturing of Multipotent Mesenchymal Stromal Cells with Autological and Allogenic Lymphocytes.

    Science.gov (United States)

    Kapranov, N M; Davydova, Yu O; Gal'tseva, I V; Petinati, N A; Bakshinskaitė, M V; Drize, N I; Kuz'mina, L A; Parovichnikova, E N; Savchenko, V G

    2018-03-01

    We studied the effect of autologous and allogeneic lymphocytes on multipotent mesenchymal stromal cells in co-culture. It is shown that changes in multipotent mesenchymal stromal cells and in lymphocytes did not depend on the source of lymphocytes. Contact with lymphocytes triggers expression of HLA-DR molecules on multipotent mesenchymal stromal cells and these cells lose their immune privilege. In multipotent mesenchymal stromal cells, the relative level of expression of factors involved in immunomodulation (IDO1, PTGES, and IL-6) and expression of adhesion molecule ICAM1 increased, while expression of genes involved in the differentiation of multipotent mesenchymal stromal cells remained unchanged. Priming of multipotent mesenchymal stromal cells with IFN did not affect these changes. In turn, lymphocytes underwent activation, expression of HLA-DR increased, subpopulation composition of lymphocytes changed towards the increase in the content of naïve T cells. These findings are important for cell therapy.

  16. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

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

  17. Cross-reactivity of human nickel-reactive T-lymphocyte clones with copper and palladium

    NARCIS (Netherlands)

    Pistoor, F. H.; Kapsenberg, M. L.; Bos, J. D.; Meinardi, M. M.; von Blomberg, M. E.; Scheper, R. J.

    1995-01-01

    Twenty Ni-reactive T-lymphocyte clones were obtained from eight different donors and analyzed for their ability to cross-react with other metals. All Ni-reactive T-lymphocyte clones were CD4+CD8- and recognized Ni in association with either HLA-DR or -DQ molecules. Based on the periodic table of the

  18. Biological Prognostic Markers in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Vladimíra Vroblová

    2009-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patient’s ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH, cytogenetic aberrations, and both intracellular ZAP- 70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

  19. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who've had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased ... leukemia. Exposure to radiation. People exposed to very high ...

  20. Molecule nanoweaver

    Science.gov (United States)

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  1. Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

    International Nuclear Information System (INIS)

    Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

    2011-01-01

    The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

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

    Science.gov (United States)

    2018-01-26

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

  3. Molecule Matters

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 4. Molecule Matters – van der Waals Molecules - History and Some Perspectives on Intermolecular Forces. E Arunan. Feature Article Volume 14 Issue 4 April 2009 pp 346-356 ...

  4. Effects of low concentrations of cadmium on immunoglobulin E production by human B lymphocytes in vitro

    International Nuclear Information System (INIS)

    Jelovcan, Sandra; Gutschi, Andrea; Kleinhappl, Barbara; Sedlmayr, Peter; Barth, Sonja; Marth, Egon

    2003-01-01

    Exposure to cadmium (Cd) can cause a variety of biological effects including alterations of immune responses in animals and humans. Both immunosuppression and immunoenhancement have been reported. The present study was aimed at investigating the consequences of exposure to Cd on the human immunoglobulin (Ig) E synthesis, using purified peripheral blood B lymphocytes and IL-4 and anti-human CD40 monoclonal antibody (a-CD40 mAb) as stimuli. Low concentrations of Cd (0.1-10 μM) markedly inhibited production of IgE in a concentration-dependent manner. IgG production, in contrast to IgE, showed a tendency towards being enhanced by Cd, although with a certain individual variability; IgM production was not affected. Cd failed to alter immediate surface expression of the activation markers CD69 and CD23 indicating that early activation events were not impaired. However, the portion of activated B cells was diminished by Cd after stimulation for more than 24 h, paralleled by a concomitant decrease in viability and a subsequent reduction in proliferation. These data suggest that the mechanism of Cd action on activated B cells involved pathways that interrupted an effectively initiated cell activation and induced a cytotoxic signal. Results from this study thus provide further evidence for and new information on the immunotoxic and immunomodulatory effects of Cd on human immune responses

  5. Radiosensitivities of sensitized lymphocytes

    International Nuclear Information System (INIS)

    Taniguchi, Kazuto

    1979-01-01

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

  6. Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70

    Directory of Open Access Journals (Sweden)

    Chuturgoon Anil A

    2011-11-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL apoptosis may also be involved in perpetuation of autoimmune processes in RA. Methods We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD, PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70 is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. Results The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes. RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. Conclusion The results suggest that while apoptosis may be initiated in RA

  7. Atkins' molecules

    CERN Document Server

    Atkins, Peters

    2003-01-01

    Originally published in 2003, this is the second edition of a title that was called 'the most beautiful chemistry book ever written'. In it, we see the molecules responsible for the experiences of our everyday life - including fabrics, drugs, plastics, explosives, detergents, fragrances, tastes, and sex. With engaging prose Peter Atkins gives a non-technical account of an incredible range of aspects of the world around us, showing unexpected connections, and giving an insight into how this amazing world can be understood in terms of the atoms and molecules from which it is built. The second edition includes dozens of extra molecules, graphical presentation, and an even more accessible and enthralling account of the molecules themselves.

  8. Interstellar Molecules

    Science.gov (United States)

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  9. Human thymic epithelial cells express functional HLA-DP molecules

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M

    1996-01-01

    T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

  10. Lymphocyte signaling: beyond knockouts.

    Science.gov (United States)

    Saveliev, Alexander; Tybulewicz, Victor L J

    2009-04-01

    The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.

  11. MRI of lymphocytic hypophysitis

    International Nuclear Information System (INIS)

    Feng Feng; Li Mingli; Li Xiaozhen; Meng Chunling; Jin zhengyu

    2005-01-01

    Objective: To describe the MR findings in patients with lymphocytic hypophysitis (LyH), and to discuss MR diagnostic value and limit in this disease entity and its differentiation with pituitary adenoma. Methods: Five pathologically proven cases of LyH were recruited in this study. The main complaints of the patients were polydipsia, polyuria, and headache. The preoperative MR images and clinical manifestations were analyzed retrospectively. Results: MR findings of the 5 patients with LyH included enlargement of pituitary gland, stalk thickening, disappearance of high signal of neurohypophysis on T 1 WI, and marked Gadolinium enhancement of the lesions. Homogeneous enhancement was found in 2 cases, while heterogeneous enhancement was in 3 cases. Involvement of the cavernous sinus and dura mater on dorsum sella and clivus were found in 2 patients. Conclusion: The diagnosis of LyH should be suggested when the enlarged pituitary gland is associated with central diabetes insipidus, and with/without dysfunction of adenohypophysis. (authors)

  12. Radioprotective effect of flavonoid quercetin on human lymphocytic cells

    International Nuclear Information System (INIS)

    Siqueira, Williams N.; Melo, Larissa S.A.; Lima, Maíra V.; Luna Filho, Ricardo L.C.; Melo, Ana M.M.A.; Silva, Edvane B.

    2017-01-01

    Several substances of synthetic and natural origin have been studied in relation to their ability to protect the body from damage caused by ionizing radiation. Among these substances, quercetin has been shown to be a molecule of natural origin with high radioprotective potential due to its antioxidant properties. The objective of this study was to determine, in vitro, the radioprotective effect of quercetin on human lymphocytes exposed to gamma radiation. Blood was irradiated at the 2.5, 3.5 and 4.5 Gy doses and then lymphocyte culture with quercetin at preselected concentrations of 37.5 and 75 μM. Subsequently, slides were prepared for analysis and quantification of the metaphases present in lymphocyte cells. The results demonstrated that irradiated lymphocytes and later exposed to quercetin presented a lower number of chromosomal alterations compared to the control group which was irradiated and not exposed to quercetin. Therefore, the results suggest a radioprotective effect of flavonoid quercetin on human lymphocytes exposed, in vitro, to ionizing radiation

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

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

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

  14. Adhesion molecules

    CERN Document Server

    Preedy, Victor R

    2016-01-01

    This book covers the structure and classification of adhesion molecules in relation to signaling pathways and gene expression. It discusses immunohistochemical localization, neutrophil migration, and junctional, functional, and inflammatory adhesion molecules in pathologies such as leukocyte decompression sickness and ischemia reperfusion injury. Highlighting the medical applications of current research, chapters cover diabetes, obesity, and metabolic syndrome; hypoxia; kidney disease; smoking, atrial fibrillation, and heart disease, the brain and dementia; and tumor proliferation. Finally, it looks at molecular imaging and bioinformatics, high-throughput technologies, and chemotherapy.

  15. Radiosensitivity of lymphocytes in vitro

    International Nuclear Information System (INIS)

    Albrecht, S.

    1979-01-01

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

  16. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

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

  17. Molecule Matters

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Molecule Matters - Dinitrogen. A G Samuelson J Jabadurai. Volume 16 Issue 12 ... Author Affiliations. A G Samuelson1 J Jabadurai1. Department of Inroganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.

  18. Molecule Matters

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 9. Molecule Matters - A Chromium Compound with a Quintuple Bond. K C Kumara Swamy. Feature Article Volume 11 Issue 9 September 2006 pp 72-75. Fulltext. Click here to view fulltext PDF. Permanent link:

  19. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... of the lymph system . Having relatives who are Russian Jews or Eastern European Jews. Signs and symptoms ... information about clinical trials is also available. To Learn More About Chronic Lymphocytic Leukemia For more information ...

  20. Crosstalk between T lymphocytes and dendritic cells.

    Science.gov (United States)

    Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique property of inducing priming and differentiation of naïve CD4+ and CD8+ T cells into helper and cytotoxic effectors. Their efficiency is due to their unique ability to process antigen, express costimulatory molecules, secrete cytokines, and migrate to tissues or lymphoid organs to prime T cells. DCs also play an important role in T-cell peripheral tolerance. There is ample evidence that the DC ability to present antigens is regulated by CD4+ helper T cells. Indeed, interactions between surface receptors and ligands expressed respectively by T cells and DCs, as well as T-cell-derived cytokines modify DC functions. This T-cell-induced modification of DCs has been called "education" or "licensing." This intimate crosstalk between DCs and T lymphocytes is key in establishing appropriate adaptive immune responses. It requires cognate interactions between T lymphocytes and DCs, which are organized in time and space by structures called immunological synapses. Here we discuss the particular aspects of immunological synapses formed between T cells and DCs and the role these organized interactions have in T-cell-DC crosstalk.

  1. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo

    2014-01-01

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

  2. Molecule Matters van der Waals Molecules

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 12. Molecule Matters van der Waals Molecules - Noble Gas Clusters are London Molecules! E Arunan. Feature Article Volume 14 Issue 12 December 2009 pp 1210-1222 ...

  3. [The lymphocyte transformation test in dermatology].

    Science.gov (United States)

    Zinn, K; Braun-Falco, O

    1976-03-01

    At first, immunologie and methodic basies of the lymphocyte transformation test are discussed. Then the results gained by this test in several dermatologic diseases are summarized. Finally, practice of the lymphocyte transformation test is critically reviewed.

  4. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

  5. Human alpha-fetoprotein and prostaglandins suppress human lymphocyte transformation by different mechanisms

    International Nuclear Information System (INIS)

    Yachnin, S.; Lester, E.P.

    1979-01-01

    The capacity of human alpha-fetoprotein (HAFP) to suppress human lymphocyte transformation is well established, although some investigators have reported negative results in their efforts to demonstrate this phenomenon. This discrepancy may reside in the fact that not all isolates of HAFP are potent inhibitors of lymphocyte transformation and that the immunosuppressive potency of various HAFP isolates may be correlated with the proportion of certain negatively charged HAFP isomers which they contain. The possibility was considered that noncovalent binding of low-molecular-weight, negatively charged molecules might be partially responsible. Since fatty acids, including certain prostaglandins (PG), are capable of binding to a partly related serum protein, namely, human serum albumin, and since certain prostaglandins are known to be potent suppressors of human lymphocyte transformation, a study was undertaken of the role which prostaglandins might play in HAFP-induced suppression of human lymphocyte transformation

  6. Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Claësson, M H

    1987-01-01

    the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native......A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form...... (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases...

  7. A microculture technique for rat lymphocyte transformation.

    Science.gov (United States)

    Lindsay, V J; Allardyce, R A

    1979-01-01

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

  8. Radiosensitivity of lymphocytes among Filipinos: final report

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  9. Short-term effects of regional irradiation on lymphocytes, T lymphocytes and eosinophils

    International Nuclear Information System (INIS)

    Chazarin, C.; Roche, H.; Bugat, R.; Pris, F.

    1983-01-01

    Twenty-three cancer patients treated only by regional irradiation were studied. Radiotherapy was delivered to the pelvis in 14 patients and to the mediastinum in 9. T lymphocytes were evaluated with the Jondal technique. Before treatment, lymphocyte counts were identical in patients and control. Decreases in total lymphocytes and T lymphocytes became significant in both groups after 40 Gy. Significant rises in eosinophil counts were found only after abdominal irradiation and seemed unrelated to variations in lymphocyte counts [fr

  10. Effects of smoking on activation markers, Fas expression and apoptosis of peripheral blood lymphocytes

    NARCIS (Netherlands)

    Bijl, Marc; Limburg, Piet; Kallenberg, Cees; Horst, G.

    Background Smoking influences numbers and function of peripheral blood lymphocytes (PBL) by a process that is badly understood. We conducted this study to evaluate whether the immune impairment of smoking might be related to changes in the expression or functionality of Fas, a cell surface molecule

  11. GENERATION OF CYTOTOXIC LYMPHOCYTES IN MIXED LYMPHOCYTE REACTIONS

    Science.gov (United States)

    Forman, James; Möller, Göran

    1973-01-01

    Generation of cytotoxic effector cells by a unidirectional mixed lymphocyte reaction (MLR) in the mouse H-2 system was studied using labeled YAC (H-2a) leukemia cells as targets. The responding effector cell displayed a specific cytotoxic effect against target cells of the same H-2 genotype as the stimulating cell population. Killing of syngeneic H-2 cells was not observed, even when the labeled target cells were "innocent bystanders" in cultures where specific target cells were reintroduced. Similar results were found with spleen cells taken from mice sensitized in vivo 7 days earlier. The effector cell was not an adherent cell and was not activated by supernatants from MLR. The supernatants were not cytotoxic by themselves. When concanavalin A or phytohemagglutinin was added to the cytotoxic test system, target and effector cells were agglutinated. Under these conditions, killing of H-2a target cells was observed in mixed cultures where H-2a lymphocytes were also the effector cells. These findings indicate that specifically activated, probably thymus-derived lymphocytes, can kill nonspecifically once they have been activated and providing there is close contact between effector and target cells. Thus, specificity of T cell killing appears to be restricted to recognition and subsequent binding to the targets, the actual effector phase being nonspecific. PMID:4269560

  12. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  13. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    Iodice, V.; Lauri, C.; Capriotti, G.; Lagana', B.; Germano, V.; D’Amelio, R.; Picchianti Diamanti, A.

    2014-01-01

    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  14. Study of the radioprotective effect of flavonoid quercetin on human lymphocytes

    International Nuclear Information System (INIS)

    Siqueira, Williams Nascimento de

    2013-01-01

    Ionizing radiation has been used in various fields of study, as medicine, industry, energy production, surgical materials sterilization, preservation and sterilization of foods, among others. These radiations may be responsible for adverse effects at molecular level in living organisms, where most important damage occurs in deoxyribonucleic acid molecule, DNA. These harmful effects caused by radiation highlights the importance of acquiring knowledge about radioprotector substances because they can act as protector of living tissue of those effects. In this research was investigated the possible radioprotective effect 'in vitro' of the flavonoid quercetin in human lymphocytes exposed to gamma radiation. At first, test was performed to evaluate the antioxidant activity of quercetin by capturing DPPH free radical molecules. Then, it was collected peripheral blood of volunteers donors. Then the samples were irradiated from linear accelerator (Siemens Primus - energy of 6 MeV and dose rate of 200 cGy/min from IMIP-PE). After samples irradiation, lymphocytes were isolated from whole blood and then the culture was carried out to obtain lymphocyte in metaphases and subsequent, analysis of chromosomal abnormalities were done at optical microscope. Statistical analysis was used Student 't' test. The results showed that quercetin at a concentration of 37.5 μM presented radioprotective against damage from gamma radiation on human lymphocytes in vitro. Have been also observed that the irradiated lymphocytes showed morphologically unchanged after undergoing the presence of the flavonoid quercetin. (author)

  15. Expression of Cellular Isoform of Prion Protein on the Surface of Peripheral Blood Lymphocytes Among Women Exposed to Low Doses of Ionizing Radiation

    International Nuclear Information System (INIS)

    Klucinski, P.; Martirosian, G.; Mazur, B.; Kaufman, J.; Hrycek, A.; Masluch, E.; Cieslik, P.

    2007-01-01

    Ionizing radiation affect the expression of adhesive and co-stimulation molecules in lymphocytes. The objective of this study was to determinate the effect of low doses of ionizing radiation on the expression of prion protein PrPc on the surface peripheral blood lymphocytes in the women operating X-ray equipment. In female workers and persons of the control group the PrPc expression on CD3 (T-lymphocytes), Cd4 (T-helper), CD8 (T-cytotoxic) and CD19 (B- lymphocytes), were tested. We conclude that in women operating X-ray equipment the relationship between low doses of ionizing radiation and expression of PrPc on lymphocytes does exist concerning CD3, CD4 and CD lymphocytes. (author)

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

    International Nuclear Information System (INIS)

    Han, T.; Dadey, B.

    1978-01-01

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

  17. Molecule Matters van der Waals Molecules

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 7. Molecule Matters van der Waals Molecules - Rg•••HF Complexes are Debye Molecules! E Arunan. Feature Article Volume 15 Issue 7 July 2010 pp 667-674. Fulltext. Click here to view fulltext PDF. Permanent link:

  18. Opinion: Interactions of innate and adaptive lymphocytes

    Science.gov (United States)

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    . Based on data from cellular binding studies, Scatchard analyses and flow cytometry, it is concluded that exogenous h beta 2m does not bind to hybrid MHC class I (MHC-I) molecules composed of mouse heavy chain/h beta 2m molecules expressed on lymphocytes of transgenic mice. Immunoprecipitation and SDS......-PAGE analysis of metabolically labelled normal C57BL/6 lymph node cells showed binding of exogenous h beta 2m to MHC-I, in particular, to the H-2Db molecule through an exchange with endogenous mouse beta 2m. In contrast to normal H-2Db molecules, hybrid H-2Db expressed on the surface of transgenic lymphocytes...... binds radiolabelled peptide in the absence of exogenous added h beta 2m suggesting that a stable fraction of hybrid H-2Db molecules is empty or contain peptides with very low affinity. In a one-way allogenic mixed lymphocyte culture, transgenic splenocytes were found to be far less stimulatory than...

  20. Damage of lymphocytes by ionizing irradiation

    International Nuclear Information System (INIS)

    Rose, H.; Moldenhauer, H.; Kehrberg, G.

    1985-01-01

    After a short review, how lymphocytes of the peripheral blood are influenced by radiotherapy, the damage of lymphocytes by whole-body irradiation is pointed out in animal experiments and after in vitro irradiation. The special sensibility of B-cells and their homogeneity in fields of radiobiology are opposed to the heterogeneity of T-cells. The radiosensibility of cytotoxic lymphocytes, suppressor cells, and helper cells are discussed. It appears, that within these functional criteria, there is a different radiosensibility, too. (author)

  1. Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

    International Nuclear Information System (INIS)

    Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

    2004-01-01

    The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

  2. Radiation sensitivity of human malignant lymphocytes

    International Nuclear Information System (INIS)

    Seshadri, R.; Matthews, C.; Morley, A.A.

    1985-01-01

    A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

  3. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  4. Lymphocytes on sounding rocket flights.

    Science.gov (United States)

    Cogoli-Greuter, M; Pippia, P; Sciola, L; Cogoli, A

    1994-05-01

    Cell-cell interactions and the formation of cell aggregates are important events in the mitogen-induced lymphocyte activation. The fact that the formation of cell aggregates is only slightly reduced in microgravity suggests that cells are moving and interacting also in space, but direct evidence was still lacking. Here we report on two experiments carried out on a flight of the sounding rocket MAXUS 1B, launched in November 1992 from the base of Esrange in Sweden. The rocket reached the altitude of 716 km and provided 12.5 min of microgravity conditions.

  5. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  6. Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

    Directory of Open Access Journals (Sweden)

    Giuseppe Scapigliati

    2018-05-01

    Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

  7. Discrimination of human cytotoxic lymphocytes from regulatory and B-lymphocytes by orthogonal light scattering

    NARCIS (Netherlands)

    Terstappen, Leonardus Wendelinus Mathias Marie; de Grooth, B.G.; ten Napel, C.H.H.; van Berkel, W.; Greve, Jan

    1986-01-01

    Light scattering properties of human lymphocyte subpopulations selected by immunofluorescence were studied with a flow cytometer. Regulatory and B-lymphocytes showed a low orthogonal light scatter signal, whereas cytotoxic lymphocytes identified with leu-7, leu-11 and leu-15 revealed a large

  8. Canine lymphocyte activating factor (LAF)

    International Nuclear Information System (INIS)

    Shifrine, M.; Whaley, C.B.; Wilson, F.D.; Taylor, N.J.

    1979-01-01

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

  9. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  10. Lymphocyte-platelet crosstalk in Graves' disease.

    Science.gov (United States)

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

  11. Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.

    Science.gov (United States)

    Cognasse, Fabrice; Acquart, Sophie; Beniguel, Lydie; Sabido, Odile; Chavarin, Patricia; Genin, Christian; Garraud, Olivier

    2005-01-01

    As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.

  12. CHARACTERISTICS OF SIGNALING PATHWAYS MEDIATING A CYTOTOXIC EFFECT OF DENDRITIC CELLS UPON ACTIVATED Т LYMPHOCYTES AND NK CELLS

    Directory of Open Access Journals (Sweden)

    T. V. Tyrinova

    2012-01-01

    Full Text Available Abstract. Cytotoxic/pro-apoptogenic effects of IFNα-induced dendritic cells (IFN-DCs directed against Т-lymphocytes and NK cells were investigated in healthy donors. Using an allogenic MLC system, it was revealed that IFN-DCs induce apoptosis of both activated CD4+ and CD8+ T-lymphocytes, and NK cells. Apoptosis of CD4+ and CD8+ T-lymphocytes induced by their interaction with IFN-DCs was mediated by various signaling pathways. In particular, activated CD4+Т-lymphocytes were most sensitive to TRAIL- и Fas/ FasL-transduction pathways, whereas activated CD8+ T-lymphocytes were induced to apoptosis via TNFα-mediated pathway. PD-1/B7-H1-signaling pathway also played a distinct role in cytotoxic activity of IFNDCs towards both types of T lymphocytes and activated NK cells. The pro-apoptogenic/cytotoxic activity of IFN-DC against activated lymphocytes may be regarded as a mechanism of a feedback regulation aimed at restriction of immune response and maintenance of immune homeostasis. Moreover, upregulation of proapoptogenic molecules on DCs under pathological conditions may lead to suppression of antigen-specific response, thus contributing to the disease progression.

  13. Management of chronic lymphocytic leukemia.

    Science.gov (United States)

    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.

  14. Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells by γ-irradiation

    International Nuclear Information System (INIS)

    Piela-Smith, T.H.; Aneiro, L.; Nuveen, E.; Korn, J.H.; Aune, T.

    1992-01-01

    A critical component of immune responsiveness is the localization of effector cells at sites of inflammatory lesions. Adhesive molecules that may play a role in this process have been described on the surfaces of both lymphocytes and connective tissue cells. Adhesive interactions of T lymphocytes with fibroblasts or endothelial cells can be inhibited by preincubation of the fibroblasts or endothelial cells with antibody to intercellular adhesion molecule 1 (CD54) or by preincubation of the T cells with antibody to lymphocyte function-associated Ag 1 (CD11a/CD18), molecules shown to be important in several other cell-cell adhesion interactions. Here the authors show that γ-irradiation of human T lymphocytes impaired their ability to adhere to both fibroblasts and endothelial cells. This impairment was not associated with a loss of cell viability or of cell surface lymphocyte function-associated Ag 1 expression. γ-Irradiation of T cells is known to result in the activation of ADP-ribosyltransferase, an enzyme involved in DNA strand-break repair, causing subsequent depletion of cellular nicotinamide adenine dinucleotide (NAD) pools by increasing NAD consumption for poly(ADP-ribose) formation. Preincubation of T cells with either nicotinamide or 3-aminobenzamide, both known inhibitors of ADP-ribosyltransferase, completely reversed the suppressive effects of γ-irradiation on T cell adhesion. The maintenance of adhesion was accompanied by inhibition of irradiation-induced depletion of cellular NAD. These experiments suggest that the impairment of cellular immune function after irradiation in vivo may be caused, in part, by defective T cell emigration and localization at inflammatory sites. 44 refs., 5 figs., 3 tabs

  15. Effects of estradiol on radiation-induced apoptosis in immunocytes of mouse

    International Nuclear Information System (INIS)

    Wu Wei; Yang Rujun; Kong Xiantao; Zhang Lingzhen; Li Bolong; Cai Jianming

    2000-01-01

    Objective: To assess the effects of estradiol on 60 Co γ-radiation induced apoptosis of splenic lymphocytes and thymocytes, and surface molecule expression of splenic lymphocytes. Methods: Mice were whole body irradiated with 4.0 Gy γ-rays. By flow cytometry and electrophoretic analysis of DNA, the changes in apoptosis of mouse immunocytes were determined. The splenic lymphocytes were analyzed by flow cytometry with fluorescent monoclonal antibodies. Results: 10 days after administration of estradiol, the characteristic DNA ladder in mice 8h after irradiation was minor than in mice without estradiol administration,indicating that the apoptotic rate reduced on flow cytometry. CD4+ T cells, CD8+ T cells and IgM+ B cells up regulated Fas, CD25 and CD69 expression, but did not so in the estradiol treated mice. Conclusion: Estradiol can block CD25, CD69 and Fas overexpression, thereby inhibiting Fas mediated apoptosis induced by γ-irradiation

  16. Lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis

    Directory of Open Access Journals (Sweden)

    An-Ran Xu

    2016-06-01

    Full Text Available Objective: To study the lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis and their correlation with disease. Methods: Children with viral encephalitis were selected as VE group, children excluded of central nervous system infection by lumbar puncture or children without central nervous system diseases but receiving surgery with spinal anesthesia were selected as control group, and then cerebrospinal fluid and serum were collected to detect lymphocyte subset contents, nerve injury molecule contents as well as inflammatory response indicators and oxidative stress response indicators. Results: CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of VE group were lower than those of control group, and both CD3+CD8+ and CD19+ were higher than those of control group; CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of children with abnormal MRI were lower than those of children with normal MRI, and both CD3+CD8+ and CD19+ were higher than those of children with normal MRI; NSE, MBP, S-100 and NPT contents in cerebrospinal fluid and serum of VE group were significantly higher than those of control group and had good correlation with lymphocyte subset contents; MMP9, TNF-α and IL-6 contents in cerebrospinal fluid of VE group were significantly higher than those of control group, and SOD and GSH-Px contents were significantly lower than those of control group and had good correlation with lymphocyte subset contents. Conclusions: CD4+/CD8+T lymphocyte ratio and NK cell content decrease, and B lymphocyte content increases in cerebrospinal fluid of children with viral encephalitis, and lymphocyte subset contents have inhibitory effect on MRI manifestation, degree of inflammatory response and oxidative stress response.

  17. Evolution and phylogeny of B lymphocytes

    Directory of Open Access Journals (Sweden)

    Fabiola Claudio-Piedras

    2016-05-01

    Full Text Available 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.

  18. Lymphocytic Pleural Effusion in Acute Melioidosis

    Directory of Open Access Journals (Sweden)

    Kuo-Mou Chung

    2007-10-01

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

  19. General Information about Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... of the lymph system . Having relatives who are Russian Jews or Eastern European Jews. Signs and symptoms ... information about clinical trials is also available. To Learn More About Chronic Lymphocytic Leukemia For more information ...

  20. Leukemia -- Chronic T-Cell Lymphocytic

    Science.gov (United States)

    ... social workers, and patient advocates. Cancer.Net Guide Leukemia - Chronic T-Cell Lymphocytic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

  1. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... between preoperatively measured neutrophil-lymphocyte ratio (NLR) – as an inflammation ... analgesic (tenoxicam – as the first drug of choice, paracetamol, tramadol, or pethidine) usage ... fracture fixation). Age, sex, type of ...

  2. Cellular immune therapy for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Kater, Arnon P.; van Oers, Marinus H. J.; Kipps, Thomas J.

    2007-01-01

    Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for

  3. Lymphocyte mobilization by dextran sulfate in beagles

    International Nuclear Information System (INIS)

    Ragan, H.A.; Debban, K.H.

    1978-01-01

    Dogs manifesting 239 Pu-induced lymphopenia responded to the lymphocyte-mobilizing agent, dextran sulfate, to a degree similar to that observed in control dogs. No life-threatening increase in prothrombin times or hemorrhagic tendencies were observed

  4. Chronic Lymphocytic Leukemia: Current Concepts.

    Science.gov (United States)

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

    2015-10-01

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

  5. How T lymphocytes see antigen

    Science.gov (United States)

    Chakraborty, Arup K.

    2009-03-01

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

  6. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  7. Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

    Science.gov (United States)

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

    1992-03-01

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

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

    Science.gov (United States)

    Mozas, Pablo; Delgado, Julio

    2016-11-18

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

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

    International Nuclear Information System (INIS)

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

    1976-01-01

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

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

    Science.gov (United States)

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

    2017-11-10

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

  11. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, Mikkel; Rasmussen, Michael

    2011-01-01

    a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules....... A pan-specific predictor of peptide–MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules. These data......In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC...

  12. Formation of Ultracold Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cote, Robin [Univ. of Connecticut, Storrs, CT (United States)

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

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

    Directory of Open Access Journals (Sweden)

    Caimi Luigi

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Kyu Hwan Kwack

    2017-01-01

    Full Text Available 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.

  15. The status of molecules

    International Nuclear Information System (INIS)

    Barnes, T.; Oak Ridge National Lab., TN; Tennessee Univ., Knoxville, TN

    1994-06-01

    This report summarizes the experimental and theoretical status of hadronic molecules, which are weakly-bound states of two or more hadrons. We begin with a brief history of the subject and discuss a few good candidates, and then abstract some signatures for molecules which may be of interest in the classification of possible molecule states. Next we argue that a more general understanding of 2 → 2 hadron-hadron scattering amplitudes will be crucial for molecule searches, and discuss some of our recent work in this area. We conclude with a discussion of a few more recent molecule candidates (notably the f o (1710)) which are not well established as molecules but satisfy some of the expected signatures. (Author)

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

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota

    2000-01-01

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

  17. Cold Rydberg molecules

    Science.gov (United States)

    Raithel, Georg; Zhao, Jianming

    2017-04-01

    Cold atomic systems have opened new frontiers at the interface of atomic and molecular physics. These include research on novel types of Rydberg molecules. Three types of molecules will be reviewed. Long-range, homonuclear Rydberg molecules, first predicted in [1] and observed in [2], are formed via low-energy electron scattering of the Rydberg electron from a ground-state atom within the Rydberg atom's volume. The binding mostly arises from S- and P-wave triplet scattering. We use a Fermi model that includes S-wave and P-wave singlet and triplet scattering, the fine structure coupling of the Rydberg atom and the hyperfine structure coupling of the 5S1/2 atom (in rubidium [3]). The hyperfine structure gives rise to mixed singlet-triplet potentials for both low-L and high-L Rydberg molecules [3]. A classification into Hund's cases [3, 4, 5] will be discussed. The talk further includes results on adiabatic potentials and adiabatic states of Rydberg-Rydberg molecules in Rb and Cs. These molecules, which have even larger bonding length than Rydberg-ground molecules, are formed via electrostatic multipole interactions. The leading interaction term of neutral Rydberg-Rydberg molecules is between two dipoles, while for ionic Rydberg molecules it is between a dipole and a monopole. NSF (PHY-1506093), NNSF of China (61475123).

  18. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA) an....../ppb. INTERPRETATION: Circulating T-lymphocyte levels may decline after surgery, regardless of implant type. Metal ions-particularly cobalt-may have a general depressive effect on T- and B-lymphocyte levels. Registered with ClinicalTrials.gov under # NCT01113762.......BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA....... RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...

  19. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  20. Chronic lymphocytic leukemia: concepts and observations

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-01-01

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

  1. Cellular energy metabolism in T-lymphocytes.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

    2015-01-01

    Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

  2. Coinhibitory molecules in cancer biology and therapy.

    Science.gov (United States)

    Mocellin, Simone; Benna, Clara; Pilati, Pierluigi

    2013-04-01

    The adaptive immune response is controlled by checkpoints represented by coinhibitory molecules, which are crucial for maintaining self-tolerance and minimizing collateral tissue damage under physiological conditions. A growing body of preclinical evidence supports the hypothesis that unleashing this immunological break might be therapeutically beneficial in the fight against cancer, as it would elicit an effective antitumor immune response. Remarkably, recent clinical trials have demonstrated that this novel strategy can be highly effective in the treatment of patients with cancer, as shown by the paradigmatic case of ipilimumab (a monoclonal antibody blocking the coinhibitory molecule cytotoxic T lymphocyte associated antigen-4 [CTLA4]) that is opening a new era in the therapeutic approach to a chemoresistant tumor such as cutaneous melanoma. In this review we summarize the biology of coinhibitory molecules, overview the experimental and clinical attempts to interfere with these immune checkpoints to treat cancer and critically discuss the challenges posed by such a promising antitumor modality. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Molecule of the Month

    Indian Academy of Sciences (India)

    Atoms in a molecule generally prefer, particularly among the neighbouring ones, certain optimmn geometrical relationships. These are manifested in specific ranges of bond lengths, bond angles, torsion angles etc. As it always happens, chemists are interested in making molecules where these 'standard relationships' are ...

  4. Molecule of the Month

    Indian Academy of Sciences (India)

    Cyclo bu tadiene (1) has been one of the most popular molecules for experimentalists and theoreticians. This molecule is unstable as . it is antiaromatic ( 4,n electrons in a cyclic array). Even though some highly substituted cyclobutadienes, for example, compound 2 and the Fe(CO)3 complex of cyclobutadiene (3) are ...

  5. Single-Molecule Spectroscopy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 2. Single-Molecule Spectroscopy: Every Molecule is Different! Kankan Bhattacharyya. General Article Volume 20 Issue 2 February 2015 pp 151-164. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Single molecule conductance

    NARCIS (Netherlands)

    Willems, R.

    2008-01-01

    This thesis represents an excursion into the world of molecular electronics, i.e. the field of research trying to use individual (organic) molecules as electronic components; in this work various experimental methods have been explored to connect individual molecules to metallic contacts and

  7. Molecules in stars

    International Nuclear Information System (INIS)

    Tsuji, T.

    1986-01-01

    Recently, research related to molecules in stars has rapidly expanded because of progress in related fields. For this reason, it is almost impossible to cover all the topics related to molecules in stars. Thus, here the authors focus their attention on molecules in the atmospheres of cool stars and do not cover in any detail topics related to circumstellar molecules originating from expanding envelopes located far from the stellar surface. However, the authors do discuss molecules in quasi-static circumstellar envelopes (a recently discovered new component of circumstellar envelopes) located near the stellar surface, since molecular lines originating from such envelopes show little velocity shift relative to photospheric lines, and hence they directly affect the interpretation and analysis of stellar spectra

  8. Lymphocytic hypophysitis: occurrence in two men.

    Science.gov (United States)

    Lee, J H; Laws, E R; Guthrie, B L; Dina, T S; Nochomovitz, L E

    1994-01-01

    Two men undergoing transsphenoidal exploration for pituitary adenoma were found to have lymphocytic hypophysitis. Both presented with frontal headaches, lethargy, and diminished libido. Laboratory investigations showed markedly depressed serum testosterone, and magnetic resonance imaging demonstrated pituitary enlargement, with optic chiasm involvement. Intraoperatively, the dura was adherent to the pituitary in each case. The resected glands were effaced by a dense lymphoplasmacytic infiltrate and fibrosis, without granulomas. Nonspecific peripheral enhancement on imaging suggested a diagnosis other than adenoma, but more experience with peripheral enhancement in lymphocytic hypophysitis is needed. The diagnosis was histological and required surgical intervention. Long-term pituitary replacement therapy is usually required.

  9. Primary lymphocytic lymphoma of lacrimal gland.

    Science.gov (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

    2017-02-01

    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

    International Nuclear Information System (INIS)

    Ghebeh, Hazem; Barhoush, Eman; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Dermime, Said

    2008-01-01

    Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T regs ). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T regs as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated in vitro and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease. Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease. A co-existence of B7-H1 + T lymphocytes and FOXP3 + T regs was evidenced by the highly significant correlation of these molecules (P < .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3 + T regs , B7-H1 + and PD-1 + TIL synergistically correlated with high histological grade (III) (P < .001), estrogen receptor negative status (P = .017), and the presence of severe lymphocytic infiltration (P = .022). Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T regs and B7-H1/PD-1 molecules

  11. Effect of low dose irradiation on subsets of T-lymphocyte of peripheral blood, spleen and tumor tissue

    International Nuclear Information System (INIS)

    Zou Huawei; Su Liaoyuan; Tian Hailin

    1998-01-01

    Purpose: In order to understand the mechanism of the stimulation effects of low dose radiation (LDR), the author observed the immune changes of T-lymphocyte subsets. Meteria and methods: Whole body of BALB/C bring-tumor mice were exposed to the doses of 5, 10, 20 and 50 cGy γ-rays. The changes of T-lymphocyte subsets in peripheral blood, spleen and tumor-infiltrating lymphocyte (TIL) were studied with flow cytometry (FCM). Results: the ratio of L 3 T 4 + /Lyt 2 + remarkable increased in the peripheral blood and spleen (p 3 T 4 + /Lyt 2 + further decreased in the TIL group of mice exposed 10 cGy (p 2 + molecules, were concentrated in the tumor tissues and they carried out the killing function to the tumor cells

  12. Dynamics of Activated Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, Amy S. [Univ. of Maryland, College Park, MD (United States)

    2016-11-16

    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  13. Dissociation in small molecules

    International Nuclear Information System (INIS)

    Dehmer, P.M.

    1982-01-01

    The study of molecular dissociation processes is one of the most interesting areas of modern spectroscopy owing to the challenges presented bt even the simplest of diatomic molecules. This paper reviews the commonly used descriptions of molecular dissociation processes for diatomic molecules, the selection rules for predissociation, and a few of the principles to be remembered when one is forced to speculate about dissociation mechanisms in a new molecule. Some of these points will be illustrated by the example of dissociative ionization in O 2

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  15. Morphometric Characterization of Small Cell Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Chisoi Anca

    2014-11-01

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

  16. Genotoxic effects of borax on cultured lymphocytes.

    Science.gov (United States)

    Pongsavee, Malinee

    2009-03-01

    The effect of borax on human chromosomes was analyzed in this study. Venous blood from 30 male students at Thammasat University, Thailand (age 18-25 years) was collected for lymphocyte cell cultures. This experiment was divided into two groups: the first group was the control group and the second group was the experimental group. The lymphocyte cells in the control group were cultured without borax. The experimental group was divided into four subgroups. The lymphocyte cells in each experimental subgroup were cultured with different concentrations of borax (0.1 mg/ml, 0.15 mg/ml, 0.2 mg/ml and 0.3 mg/ml). Human chromosomes were studied for abnormalities through Giemsa-staining and G-banding. The results show that the numbers of metaphase plates (the metaphase plate which contained 46 chromosomes; 46, XY) and metaphase chromosomes were reduced when lymphocyte cells were cultured with 0.15 mg/ml (57.2%), 0.2 mg/ml (50.8%) and 0.3 mg/ml (42.3%) concentrations of borax. There was a statistically significant difference between the control and experimental subgroups (p borax concentration experimental subgroup. This shows that borax (at 0.15, 0.2 and 0.3 mg/ml concentrations) affects the cell and human chromosomes (both numerical and structural abnormalities). Borax may cause human chromosome abnormalities and lead to genetic defects.

  17. Chronic lymphocytic leukaemia manifestating as exfoliative dermatitis

    Directory of Open Access Journals (Sweden)

    Dhir R

    1995-01-01

    Full Text Available A 60-year-old patient reported with a history of redness and peeling of the skin, and sensations of chills and tightness of the skin of three months duration. Clinical examination revealed exfoliative dermatitis, generalised lymphadenopathy and hepatosplenomegely. A peripheral smear showed features of chronic lymphocytic leukaemia.

  18. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  19. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could...

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

    Lifescience Database Archive (English)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-11-15

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

  2. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst

    2007-01-01

    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  3. Electron-molecule collisions

    CERN Document Server

    Takayanagi, Kazuo

    1984-01-01

    Scattering phenomena play an important role in modern physics. Many significant discoveries have been made through collision experiments. Amongst diverse kinds of collision systems, this book sheds light on the collision of an electron with a molecule. The electron-molecule collision provides a basic scattering problem. It is scattering by a nonspherical, multicentered composite particle with its centers having degrees of freedom of motion. The molecule can even disintegrate, Le., dissociate or ionize into fragments, some or all of which may also be molecules. Although it is a difficult problem, the recent theoretical, experimental, and computational progress has been so significant as to warrant publication of a book that specializes in this field. The progress owes partly to technical develop­ ments in measurements and computations. No less important has been the great and continuing stimulus from such fields of application as astrophysics, the physics of the earth's upper atmosphere, laser physics, radiat...

  4. Molecules to Materials

    Indian Academy of Sciences (India)

    evolved as a new line of thinking wherein a single molecule or perhaps a collection .... In photonic communication processes, laser light has to be modulated and .... The author wishes to thank G Rajaram for a critical reading of the manuscript.

  5. Single-Molecule Spectroscopy

    Indian Academy of Sciences (India)

    IAS Admin

    overall absorption spectrum of a molecule is a superposition of many such sharp lines .... dilute solution of the enzyme and the substrate over few drops of silicone oil placed ..... Near-field Scanning Optical Microscopy (NSOM): Development.

  6. Quantum dot molecules

    CERN Document Server

    Wu, Jiang

    2014-01-01

    This book reviews recent advances in the exciting and rapidly growing field of quantum dot molecules (QDMs). It offers state-of-the-art coverage of novel techniques and connects fundamental physical properties with device design.

  7. Molecule of the Month

    Indian Academy of Sciences (India)

    Molecule of the Month - Adamantane - A Plastic Piece of Diamond. J Chandrasekhar. Volume 16 Issue 12 ... Keywords. Adamantane; diamondoid systems; plastic crystals. ... Resonance – Journal of Science Education | News. © 2017 Indian ...

  8. Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2.

    Science.gov (United States)

    Cui, Lei; Yin, Shuo; Liu, Wei; Li, Ningli; Zhang, Wenjie; Cao, Yilin

    2007-06-01

    Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less immunogenic and immunosuppressive. Previous study showed that primary cultures of human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties with other MSCs. However, whether passaged human ADSCs can retain their immunomodulatory effect after in vitro expansion remains unknown. In addition, the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated. This study aimed to investigate these issues by using passaged human ADSCs as an in vitro study model. Flow cytometry showed that passaged ADSCs expressed human leukocyte antigen (HLA) class I but not class II molecules, which could be induced to express to a high level with interferon-gamma (IFN-gamma) treatment. The study found that passaged ADSCs could not elicit lymphocyte proliferation after co-culturing with them, even after IFN-gamma treatment. In addition, either IFN-gamma-treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)-stimulated lymphocyte proliferation. Moreover, passaged ADSCs could serve as the third-party cells to inhibited two-way mixed lymphocyte reaction (MLR). Further study using a transwell system also showed that this type of immunosuppressive effect was not cell-cell contact dependent. In defining possible soluble factors, we found that passaged ADSCs significantly increased their secretion of prostaglandin E2 (PGE2), but not transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF), when they were co-cultured with MLR. Furthermore, the result demonstrated that only PGE2 production inhibitor indomethacine, but not TGF-beta- and HGF-neutralizing antibodies, could significantly counteract ADSC-mediated suppression on allogeneic lymphocyte proliferation. These results indicated that in vitro expanded ADSCs retain low immunogenicity and immunosuppressive effect, and PGE2 might be the major soluble factor involved in the in vitro inhibition of

  9. Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE) : relation to lymphocyte activation and disease activity

    NARCIS (Netherlands)

    Bijl, M; Horst, G; Limburg, PC; Kallenberg, CGM

    2001-01-01

    Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production, Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased Susceptibility to Fas-mediated apoptosis in

  10. Differential effect of gamma-irradiated and heat-treated lymphocytes on T cell activation, and interleukin-2 and interleukin-3 release in the human mixed lymphocyte reaction

    International Nuclear Information System (INIS)

    Loertscher, R.; Abbud-Filho, M.; Leichtman, A.B.; Ythier, A.A.; Williams, J.M.; Carpenter, C.B.; Strom, T.B.

    1987-01-01

    Heat-inactivated (45 degrees C/1 hr) lymphocytes selectively activate suppressor T cells in the mixed lymphocyte reaction (MLR), while no significant proliferation and cytotoxic T lymphocyte activation can be detected. It is not well understood why hyperthermic treatment abolishes the stimulatory capacity of lymphocytes since HLA-DR molecules remain detectable immediately following heat exposure. In order to further characterize the requirements for Ts activation we studied the effects of hyperthermic treatment on cellular protein and DNA synthesis and cell surface protein expression in proliferating T and B cells; interleukin (IL)-1, IL-2, and IL-3 release following allogeneic stimulation with heat treated cells (HMLR); and IL-2 receptor expression as an indicator of T cell activation in the HMLR. Hyperthermic treatment reduced cellular protein synthesis as estimated by 14 C-leucine uptake to about 15%, and DNA synthesis ( 3 H-thymidine incorporation) to about 5% of untreated control cells. In contrast to y-irradiated cells, viability of heated cells rapidly declined within the first 24 hr. Hyperthermic treatment doubled binding of mouse immunoglobulin paralleled by an increased expression of IL-2 and transferrin receptors, while expression of HLA-DR and 4F2 proteins appeared unchanged. Stimulation with heated cells triggered the release of IL-1- and an IL-3-like bioactivity but did not induce IL-2 synthesis and/or release, thus explaining the lack of proliferation in the HMLR. Addition of exogenous IL-2 but not IL-1 restored HMLR proliferation. A comparison of allostimulation with y-irradiated and heat-treated cells revealed that significantly fewer T cells were induced to express IL-2 receptors at day 3 (14% vs. 8%, P less than 0.001) and at day 6 (42% vs. 21%, P less than 0.05) with heat-inactivated stimulators

  11. Different anti-CD21 antibodies can be used to discriminate developmentally and functionally different subsets of B lymphocytes in circulation of pigs

    Czech Academy of Sciences Publication Activity Database

    Šinkora, Marek; Štěpánová, Kateřina; Šinkorová, Jana

    2013-01-01

    Roč. 39, č. 4 (2013), s. 409-418 ISSN 0145-305X R&D Projects: GA ČR GAP502/10/0038; GA MŠk ME09089 Institutional support: RVO:61388971 Keywords : Porcine immune system * Cell surface molecules * Lymphocyte subpopulations Subject RIV: EC - Immunology Impact factor: 3.705, year: 2013

  12. Effect of Vibrio cholerae neuraminidase on the mitogen response of T lymphocytes. I. Enhancement of macrophage T-lymphocyte cooperation in concanavalin-A-induced lymphocyte activation.

    Science.gov (United States)

    Knop, J

    1980-12-01

    Vibrio cholerae neuraminidase (VCN) enhances the immune response of lymphocytes in various systems, such as antigen- and mitogen-induced blastogenesis, mixed lymphocyte culture (MLC) and tumor-cell response. We used macrophage-depleted and reconstituted murine lymph-node T-cells to investigate the effect of VCN on macrophage-T-lymphocyte co-operation in Con-A-induced lymphocyte activation. In unfractionated lymph-node cells VCN enhanced the Con-A-induced lymphocyte activation as measured by 3H-thymidine (3H-dThd) incorporation. Removing macrophages from the cells resulted in a significantly diminished response. In addition the enhancing effect of VCN was greatly reduced. Reconstitution of the lymphocyte cultures with macrophages in increasing numbers and from various sources rstored the lymphocyte response and the enhancing effect of VCN. VCN proved to be most efficient in cultures reconstituted with normal peritoneal macrophages. Some effect was also observed using bone-marrow-derived (BM) macrophages. However, higher numbers of normal PE macrophages in the presence of VCN inhibited lymphocyte activation, and inhibition by thioglycollate-broth-induced macrophages was considerably increased by VCN. These results suggest that VCN acts by increasing the efficiency of macrophage-T lymphocyte interaction.

  13. Electron-molecule collisions

    International Nuclear Information System (INIS)

    Shimamura, I.; Takayanagi, K.

    1984-01-01

    The study of collision processes plays an important research role in modern physics. Many significant discoveries have been made by means of collision experiments. Based on theoretical, experimental, and computational studies, this volume presents an overview detailing the basic processes of electron-molecule collisions. The editors have collected papers-written by a group of international experts-that consider a diverse range of phenomena occurring in electronmolecule collisions. The volume discusses first the basic formulation for scattering problems and then gives an outline of the physics of electron-molecule collisions. The main topics covered are rotational transitions, vibrational transitions, dissociation of molecules in slow collisions, the electron-molecule collision as a spectroscopic tool for studying molecular electronic structures, and experimental and computational techniques for determining the cross sections. These well-referenced chapters are self-contained and can be read independently or consecutively. Authoritative and up-to-date, Electron-Molecule Collisions is a useful addition to the libraries of students and researchers in the fields of atomic, molecular, and chemical physics, and physical chemistry

  14. MOLECULES IN η CARINAE

    International Nuclear Information System (INIS)

    Loinard, Laurent; Menten, Karl M.; Güsten, Rolf; Zapata, Luis A.; Rodríguez, Luis F.

    2012-01-01

    We report the detection toward η Carinae of six new molecules, CO, CN, HCO + , HCN, HNC, and N 2 H + , and of two of their less abundant isotopic counterparts, 13 CO and H 13 CN. The line profiles are moderately broad (∼100 km s –1 ), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO + do not appear to be underabundant in η Carinae. On the other hand, molecules containing nitrogen or the 13 C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of η Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  15. Characteristics of T lymphocyte subpopulations 

    Directory of Open Access Journals (Sweden)

    Paulina Niedźwiedzka-Rystwej

    2013-05-01

    Full Text Available The paper describes the characteristics, receptor profile and functions of T lymphocyte subpopulations (helper, cytotoxic, regulatory, memory and others. Among T helper cells one can enumerate Th0, Th1, Th2, Th9, Th17, Th22, TFH and nTh2, while T cytotoxic cells include Tc, NKT, Tγδ, and T CD8αα (IEL. Among regulatory cells there are nTreg, iTreg, TR1, and iTR35, as well as T lymphocytes with CD8, such as CD8 CD122 , CD8 CD28-, and CD11c CD8 . And among memory T cells there are Tcm and Tem. Moreover, there are some so-called other T cells, such as Tn (T αβ CD4 and T αβ CD8 , T exhausted and T anergic. 

  16. Lymphocytic subsets and low-dose exposure

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Eybl, E.

    1993-03-01

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

  17. Analysis of monoclonal antibodies reactive with molecules upregulated or expressed only on activated lymphocytes.

    Science.gov (United States)

    Davis, W C; Naessens, J; Brown, W C; Ellis, J A; Hamilton, M J; Cantor, G H; Barbosa, J I; Ferens, W; Bohach, G A

    1996-08-01

    Monoclonal antibodies potentially specific for antigens expressed or upregulated on activated leukocytes were selected for further analysis from the panel submitted to the third international workshop on ruminant leukocyte antigens. The kinetics of expression of these activation antigens on resting peripheral mononuclear cells (PBMC) and PBMC stimulated with concanavalin A or staphylococcal superantigen SECI for 4, 24 or 96 h were compared, as well as their appearance on various subsets of cells. For some of them, a molecular mass could be determined after immunoprecipitation from radio-labeled, lectin-stimulated cells. Based on the results from the clustering, kinetic studies and biochemical data, evidence was gathered for assigning two additional mAbs to cluster BoCD25 (IL-2 receptor) and two mAbs to cluster BoCD71 (transferrin receptor). Four mAbs recognized an early activation antigen predominantly expressed on gamma delta T cells in short-term cultures. A number of other activation antigens were further characterized.

  18. Cytotoxic T lymphocyte associated molecule -4 (CTLA-4 gene polymorphisms in ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Sirous Naeimi

    2010-09-01

    Full Text Available Background: Ovarian cancer is a relatively common cancer among postmenopausal women. Nowadays, there is controversy about immunotherapy of ovarian cancer patients with interleukins such as interferon to reach better out come in prognosis of patients under chemotherapy. CTLA-4 is a gene, which has an important role in homeostasis and regulation of immune response. Inhibitory nature of CTLA-4 is proved to be of significance in autoimmune diseases as well as in cancer. In this study we intend to find out the relationship between polymorphisms of this gene at the sites of +49 A/G and -318 C/T and ovarian cancer.Methods: The polymorphisms of the CTLA-4 gene at the sites of +49 A/G exon and -318 C/T promoter were investigated. Blood samples of 73 patients with ovarian cancer and 115 healthy subjects used for DNA extraction. Two groups genotypes and alleles were determined using PCR method and compared by statistical t-student test.Results: There was no statistically significant difference in genotypes and alleles prevalence of +49 A/G and -317 C/T between two groups (p>0.05.Conclusion: Further researches with larger sample size while paying attention to the relation between the gene polymorphism and stage and type of tumor is recommended.

  19. Electron Accumulative Molecules.

    Science.gov (United States)

    Buades, Ana B; Sanchez Arderiu, Víctor; Olid-Britos, David; Viñas, Clara; Sillanpää, Reijo; Haukka, Matti; Fontrodona, Xavier; Paradinas, Markos; Ocal, Carmen; Teixidor, Francesc

    2018-02-28

    With the goal to produce molecules with high electron accepting capacity and low reorganization energy upon gaining one or more electrons, a synthesis procedure leading to the formation of a B-N(aromatic) bond in a cluster has been developed. The research was focused on the development of a molecular structure able to accept and release a specific number of electrons without decomposing or change in its structural arrangement. The synthetic procedure consists of a parallel decomposition reaction to generate a reactive electrophile and a synthesis reaction to generate the B-N(aromatic) bond. This procedure has paved the way to produce the metallacarboranylviologen [M(C 2 B 9 H 11 )(C 2 B 9 H 10 )-NC 5 H 4 -C 5 H 4 N-M'(C 2 B 9 H 11 )(C 2 B 9 H 10 )] (M = M' = Co, Fe and M = Co and M' = Fe) and semi(metallacarboranyl)viologen [3,3'-M(8-(NC 5 H 4 -C 5 H 4 N-1,2-C 2 B 9 H 10 )(1',2'-C 2 B 9 H 11 )] (M = Co, Fe) electron cumulative molecules. These molecules are able to accept up to five electrons and to donate one in single electron steps at accessible potentials and in a reversible way. By targeted synthesis and corresponding electrochemical tests each electron transfer (ET) step has been assigned to specific fragments of the molecules. The molecules have been carefully characterized, and the electronic communication between both metal centers (when this situation applies) has been definitely observed through the coplanarity of both pyridine fragments. The structural characteristics of these molecules imply a low reorganization energy that is a necessary requirement for low energy ET processes. This makes them electronically comparable to fullerenes, but on their side, they have a wide range of possible solvents. The ET from one molecule to another has been clearly demonstrated as well as their self-organizing capacity. We consider that these molecules, thanks to their easy synthesis, ET, self-organizing capacity, wide range of solubility, and easy processability, can

  20. REACTIVITY OF BLOOD LYMPHOCYTES IN PULMONARY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    R. R. Khasanova

    2009-01-01

    Full Text Available Evaluation of proliferative and IL-2-producing activity of peripheral blood lymphocytes wasperformed, using cultural methods, in patients with drug-sensitive and drug-resistant infiltrative pulmonary tuberculosis. The cell testing was performed at basal level and following in vitro stimulation with recombinant IL-2 and M. tuberculosis antigens. It was established that clinical course of infiltrative pulmonary tuberculosis, independently on drug sensitivity/resistance of the infectious pathogen, is accompanied by suppression of spontaneous lymphoproliferation. The levels of induced IL-2 production in drug-sensitive tuberculosis proved to be increased, whereas a reserve of IL-2-secreting reactivity of blood lymphocytes was lower than in drugresistant infection. Also, it was revealed that the level of lymphoproliferative response induced by IL-2, does not depend on clinical variant of tuberculosis, whereas stimulation of IL-2 production in blood lymphocytes is attained only in cases of drug-resistant tuberculosis variant.

  1. Decreased lymphocyte dopamine transporter in romantic lovers.

    Science.gov (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana

    2017-06-01

    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  2. Radiosensitivity of human lymphocytes and thymocytes

    International Nuclear Information System (INIS)

    Kwan, D.K.; Norman, A.

    1977-01-01

    The in vitro survival of human peripheral blood lymphocytes and thymocytes was measured 4 days following graded doses of γ radiation. Results indicate considerable heterogeneity among lymphocyte subpopulations with respect to radiosensitivity. Total T lymphocytes were characterized by rosette formation with neuraminidase-treated sheep red blood cells (nSRBC); early T (T/sub E/) cells, by early rosettes; and B cells, by their inability to form nSRBC rosettes. Late T (T/sub L/) cells were defined as T -- T/sub E/. Survival curves of T, T/sub E/, and B cells are biphasic. The radiosensitive and radioresistant components of T, T/sub E/, and B cells all have a D 0 of about 50 and 550 rad, respectively. B cells appeared to be slightly more radiosensitive than T cells. T/sub L/ cells and thymocytes, however, appeared to be homogeneous with respect to radiosensitivity, both having D 0 values of about 135 rad. The survival of T cells in mixed T and B cell cultures resembled that of separated T cells, suggesting that ionizing radiation has no significant effect on rosette formation. It also indicates that interactions of T and B cells do not significantly affect their radiation responses

  3. Robot system for preparing lymphocyte chromosome

    International Nuclear Information System (INIS)

    Hayata, Isamu; Furukawa, Akira; Yamamoto, Mikio; Sato, Koki; Tabuchi, Hiroyoshi; Okabe, Nobuo.

    1992-01-01

    Towards the automatization of the scoring of chromosome aberrations in radiation dosimetry with the emphasis on the improvement of biological preparations, the conventional culture and harvesting method was modified. Based on this modified method, a culture and harvest robotic system (CHROSY) for preparing lymphocyte chromosome was developed. The targeted points of the modification are as in the preparing lymphocyte chromosome was developed. The targeted points of the modification are as in the following. 1) Starting culture with purified lymphocytes in a fixed cell number. 2) Avoiding the loss of cells in changing the liquids following centrifugalization. 3) Keeping the quantity of the liquids to be applied to the treatments of cells fixed. 4) Building a system even a beginner can handle. System features are as follows. 1) Operation system: Handling robot having 5 degrees of freedom; a rotator incubator with an automatic sliding door; units for setting and removing pipette tips; a centrifuge equipped with a position adjuster and an automatic sliding door; two aluminium block baths; two nozzles as pipettes and aspirators connected to air pumps; a capping unit with a nozzle for CO 2 gas; a compressor; and an air manipulated syringe. 2) Control system; NEC PC-9801RX21 with CRT; and program written in Basic and Assembly languages on MS-DOS. It took this system 2 hours and 25 minutes to harvest 2 cultures. A fairly good chromosome slide was made from the sample harvested by CHROSY automatically. (author)

  4. Lymphocytic hypophysitis masquerading as pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Rajneesh Mittal

    2012-01-01

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

  5. Normal lymphocyte immunophenotype in an elderly population

    Directory of Open Access Journals (Sweden)

    Sâmia Macedo Queiroz Mota Castellão Tavares

    2014-06-01

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

  6. To the nucleolar bodies (nucleoli) in cells of the lymphocytic lineage in patients suffering from B - chronic lymphocytic leukemia.

    Science.gov (United States)

    Smetana, K; Karban, J; Trneny, M

    2010-01-01

    The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or

  7. Novel treatments for chronic lymphocytic leukemia and moving forward.

    Science.gov (United States)

    Brown, Jennifer R; Porter, David L; O'Brien, Susan M

    2014-01-01

    The last several years have seen an explosion of novel therapies for chronic lymphocytic leukemia (CLL). These include the antibody obintutuzumab (GA-101), as well as small-molecule inhibitors of key pathways involved in the pathogenesis of CLL, specifically the B-cell receptor (BCR) pathway (especially Bruton's tyrosine kinase [BTK] and P13K), and the antiapoptotic pathway (especially BCL-2). We will consider each in turn, focusing on the molecules most advanced in clinical development. There has also been extensive development in rewiring the patient's own immune system to treat CLL. This has been done through modifying autologous T cells to express a chimeric antigen receptor (CAR). Thus far all CAR-T preparations have targeted the CD19 antigen. This is a good rational for B-cell malignancies as CD19 expression is limited to B-cell malignancies and normal B cells. The in vivo amplification of the transduced T cells relies on signaling and co-signaling domains and provides significant killing of CLL cells. As exciting as these novel agents and approaches are, they obviously beg the question, will chemotherapy as a treatment for CLL soon be obsolete? Although chemotherapy is associated with known short-term toxicities, it has the advantage of being completed in a short period of time and being relatively inexpensive in comparison to novel therapies. In addition, long-term follow-up of results with chemoimmunotherapy have now identified a group of patients whose remissions are maintained for more than 10 years. An important question that will arise going forward is how to incorporate novel agents without eliminating the long term benefits possible with chemoimmunotherapy in a subset of patients with CLL.

  8. Molecule of the Month

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 2. Molecule of the Month Isomers of Benzene - Still Pursuing Dreams. J Chandrasekhar. Feature Article Volume 1 Issue 2 February 1996 pp 80-83. Fulltext. Click here to view fulltext PDF. Permanent link:

  9. Atoms, Molecules, and Compounds

    CERN Document Server

    Manning, Phillip

    2007-01-01

    Explores the atoms that govern chemical processes. This book shows how the interactions between simple substances such as salt and water are crucial to life on Earth and how those interactions are predestined by the atoms that make up the molecules.

  10. Electrons in Molecules

    Indian Academy of Sciences (India)

    structure and properties (includingreactivt'ty) - both static (independent of time) and ... Furthermore, since the energy of H2 + in the ground state must be lower than that of .... (Figure 2b); note also that dp is positive in parts of the antibinding regions behind the two ... But, now both the sizes and shapes of molecules enter into.

  11. Molecule of the Month

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Molecule of the Month - A Stable Dibismuthene - A Compound with a Bi-Bi Double Bond. V Chandrasekhar. Volume 16 ... Author Affiliations. V Chandrasekhar1. Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India.

  12. OMG: Open molecule generator

    NARCIS (Netherlands)

    Peironcely, J.E.; Rojas-Chertó, M.; Fichera, D.; Reijmers, T.; Coulier, L.; Faulon, J.-L.; Hankemeier, T.

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical

  13. Molecule-based magnets

    Indian Academy of Sciences (India)

    Administrator

    Employing self-assembly methods, it is possible to engineer a bulk molecular material ... synthesis of molecular magnets in 1986, a large variety of them have been synthesized, which can be catego- ... maintained stably per organic molecule, stabilization of a ..... rotating freely under an applied field because it is a magne-.

  14. Molecule of the Month

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 5. Molecule of the Month Molecular–Chameleon: Solvatochromism at its Iridescent Best! Photon Rao. Feature Article Volume 2 Issue 5 May 1997 pp 69-72. Fulltext. Click here to view fulltext PDF. Permanent link:

  15. Exotic helium molecules

    International Nuclear Information System (INIS)

    Portier, M.

    2007-12-01

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range 4 He 2 (2 3 S 1 -2 3 P 0 ) molecule, or a 4 He 2 (2 3 S 1 -2 3 S 1 ) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 ± 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range 4 He 2 (2 3 S 1 -2 3 S 1 ) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime τ = (1.4 ± 0.3) μs is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  16. OMG: Open Molecule Generator.

    Science.gov (United States)

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-09-17

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  17. OMG: Open Molecule Generator

    Directory of Open Access Journals (Sweden)

    Peironcely Julio E

    2012-09-01

    Full Text Available Abstract Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG, which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  18. Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

    2015-09-08

    B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process.

  19. Chromium picolinate induced apoptosis of lymphocytes and the signaling mechanisms thereof

    International Nuclear Information System (INIS)

    Jana, Mahadevan; Rajaram, Anantanarayanan; Rajaram, Rama

    2009-01-01

    Cr(III)(picolinate) 3 [Cr(III)(pic) 3 ] is currently used as a nutritional supplement and for treating Type-2 diabetes. The effect of Cr(III)(pic) 3 uptake in peripheral blood lymphocytes is investigated in this study. From the cytotoxicity data, DNA fragmentation pattern, Annexin V staining, TUNEL positivity and the ultrastructural characteristics such as chromatin condensation and formation of apoptotic bodies, it is clear that Cr(III)(pic) 3 induces a concentration dependent apoptosis. It is shown that reactive oxygen species (ROS) produced by treatment with Cr(III)(pic) 3 leads to apoptosis, since we find that pretreatment with N-acetyl cysteine inhibits the process. Using Western blotting technique and fluorescence measurements, the downstream signaling molecules have also been identified. Cr(III)(pic) 3 treatment leads to collapse of the mitochondrial membrane potential, Bax expression, increase in cytosolic cytochrome c content and active caspase-3 and DNA fragmentation and all these manifestations are reduced by pretreating the lymphocytes with N-acetyl cysteine. Thus, it is shown that Cr(III)(pic) 3 is cytotoxic to lymphocytes with ROS and mitochondrial events playing a role in bringing about apoptosis.

  20. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

    Science.gov (United States)

    Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

    2016-07-01

    Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

  1. Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

    Science.gov (United States)

    Häyry, P.; Defendi, V.

    1970-01-01

    We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

  2. Deleterious effects of lymphocytes at the early stage of neurodegeneration in an animal model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Nakatsuji Yuji

    2011-02-01

    Full Text Available Abstract Background Non-neuronal cells, such as microglia and lymphocytes, are thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS. Previous studies have demonstrated neuroprotective effects of lymphocytes at the end stage of ALS, partly through induction of alternatively activated microglia (M2 microglia, which are neuroprotective. In this study, we investigated the role of lymphocytes in the early stage of the disease using an animal model of inherited ALS. Methods We established a transgenic mouse line overexpressing the familial ALS-associated G93A-SOD1 mutation (harboring a single amino acid substitution of glycine to alanine at codon 93 with depletion of the Rag2 gene (mSOD1/RAG2-/- mice, an animal model of inherited ALS lacking mature lymphocytes. Body weights, clinical scores and motor performance (hanging wire test of mSOD1/RAG2-/- mice were compared to those of mutant human SOD1 transgenic mice (mSOD1/RAG2+/+ mice. Activation of glial cells in the spinal cords of these mice was determined immunohistochemically, and the expression of mRNA for various inflammatory and anti-inflammatory molecules was evaluated. Results Clinical onset in mSOD1/RAG2-/- mice was significantly delayed, and the number of lectin-positive cells in spinal cord was increased at the early stage of disease when compared to mSOD1/RAG2+/+ mice. Quantitative RT-PCR confirmed that mRNA for Ym1, an M2 microglial-related molecule, was significantly increased in mSOD1/RAG2-/- mouse spinal cords at the early disease stage. Conclusions Compared with mSOD1/RAG2+/+ mice, mSOD1/RAG2-/- mice displayed delayed onset and increased M2 microglial activation at the early stage of disease. Thus, lymphocytes at the early pathological phase of ALS display a deleterious effect via inhibition of M2 microglial activation.

  3. The effects of low dose radiation (LDR) on lymphocytes

    International Nuclear Information System (INIS)

    Su Liaoyuan; Du Zeji; Tian Hailin; Zhao Yujie; Zou Huawei; Zhou Jianhua; Kong Xiangrong; Zhang Jianhua; Shen Wei

    2001-01-01

    LDR could stimulate lymphocyte transformation for adults, children and infants. The effect of LDR on lymphocytes in malnourished children was lower, but higher on lymphocytes in cord blood. The effect of LDR on CD 4 + cells in adult persons was higher than that on CD + cells. NK cells were radioresistant. The stimulative effect of LDR on NK activity in tumor patients was lower than that in normal individuals. For the mice with tumors, LDR could increase the ratio of L 3 T 4 cells in blood, spleen and the number of cytotoxic T cells in the tumors. Extracellular fluid of the lymphocytes operated by LDR could also stimulate the lymphocyte transformation. The preliminary LDR could decrease the injuries to macromolecules, membrane antigens and chromosomes in lymphocytes which were induced by high dose radiation. The LDR- induced protein might be found from mouse spleen cells, and this protein could increase immune function in human and animals

  4. Effect of radiotherapy on lymphocyte cytotoxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wasserman, J; Melen, B [Central Microbiological Laboratory, Stockholm County Council (Sweden); Blomgren, H; Glas, U; Perlmann, P

    1975-11-01

    The cytotoxic functions of highly purified blood lymphocytes from patients with breast cancer were studied before and after radiotherapy. Addition of PHA or of rabbit antibodies to target cells (chicken erythrocytes) were chosen as two means of inducing lymphocyte cytotoxicity in vitro. The proportion of T and non-T lymphocytes was determined by means of E and EAC rosette tests. The antibody-induced cytotoxicity of lymphocytes decreased following radiotherapy while that mediated by PHA remained unchanged. There was some reduction in the percentage of EAC rosette-forming cells. These results, as well as earlier observations, suggest that the decrease in the peripheral blood of the proportion of lymphocytes with receptors for activated complement is responsible for changes in the antibody-mediated lymphocyte cytotoxicity.

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

    Science.gov (United States)

    2018-05-10

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

  6. Further studies of immunoglobulin synthesis by guinea-pig leukaemic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hough, D W; Chapple, J C; Stevenson, F K; Stevenson, G T [Southampton General Hospital (UK)

    1978-05-01

    The L/sub 2/C leukemia is a B-lymphocytic neoplasm of strain 2 guinea pigs maintained by passaging in vivo. It synthesizes ..mu.. and lambda immunoglobulin chains. These combine to form monomeric (7S) IgM molecules which are inserted into the plasma membrane. From here they are shed as monomeric IgM and as a species of higher molecular weight which has not been further defined. The synthesis of lambda chain is in excess of that required for the IgM molecule, the surplus being exported directly from the cell without any intervening phase in the plasma membrane. Quantitative estimates of synthetic rates and pool sizes for these immunoglobulin species are presented.

  7. Nucleolar size in lymphocytes and haemocytes of different species

    Directory of Open Access Journals (Sweden)

    J Berger

    2009-08-01

    Full Text Available The number of nucleoli in a cell and nucleolar area vary according to the cell. We compared nucleoli in mammalian circulating lymphocytes and insect circulating haemocytes. An increased nucleolar coefficient correlated with a lowered nucleoli size. The smaller nucleolar size in mammalian lymphocytes indicates a lower proteosynthetic cellular activity in both mammalian lymphocytes and insect haemocytes. Moreover, in insect haemocytes, the smaller size of the nucleoli may reflect a lowered potential to transform into another cell type.

  8. Cell kinetic and radiosensitivity of PHA stimulated goat lymphocytes

    International Nuclear Information System (INIS)

    Debuyst, B.; Rosenthal, M.; Leonard, A.

    1982-01-01

    The harlequin-staining method has been used to study the cell kinetic of goat peripheral blood lymphocytes stimulated by phytohemagglutinin and to assess their radiosensitivity. At 48 h, the standardized culture time employed for human lymphocytes, 71% of the goat lymphocytes are in first mitosis, 23% are in second mitosis and 5% in third. Irradiation with 200 rads X-rays induces an average of 24,5 dicentric chromosomes per hundred cells in first mitosis [fr

  9. Influence of immunomodulators on the lymphokine secretion of irradiated lymphocytes

    International Nuclear Information System (INIS)

    Kowalczyk-Bronisz, S.H.

    1986-01-01

    Spleen lymphocytes derived from guinea pigs loose their ability to secrete lymphokines induced by Con A after treatment with irradiation (500 and 750 mC/kg). In the presence of the immunomodulators isoprinosine, levamisole and the thymosine-like factor TFX the lymphocytes are again capable of secreting lymphokines. After treatment with immunomodulators in dosages between 10 and 100 μg/ml the migration inhibition activity for macrophages and the chemotactic activity for polymorphonuclear granulocytes produced by lymphocytes were restored. (author)

  10. Single-Molecule Nanomagnets

    Science.gov (United States)

    Friedman, Jonathan R.; Sarachik, Myriam P.

    2010-04-01

    Single-molecule magnets straddle the classical and quantum mechanical worlds, displaying many fascinating phenomena. They may have important technological applications in information storage and quantum computation. We review the physical properties of two prototypical molecular nanomagnets, Mn12-acetate and Fe8: Each behaves as a rigid, spin-10 object and exhibits tunneling between up and down directions. As temperature is lowered, the spin-reversal process evolves from thermal activation to pure quantum tunneling. At low temperatures, magnetic avalanches occur in which the magnetization of an entire sample rapidly reverses. We discuss the important role that symmetry-breaking fields play in driving tunneling and in producing Berry-phase interference. Recent experimental advances indicate that quantum coherence can be maintained on timescales sufficient to allow a meaningful number of quantum computing operations to be performed. Efforts are under way to create monolayers and to address and manipulate individual molecules.

  11. Superexcited states of molecules

    International Nuclear Information System (INIS)

    Nakamura, Hiroki; Takagi, Hidekazu.

    1990-01-01

    The report addresses the nature and major features of molecule's superexcited states, focusing on their involvement in dynamic processes. It also outlines the quantum defect theory which allows various processes involving these states to be treated in a unified way. The Rydberg state has close relation with an ionized state with a positive energy. The quantum defect theory interprets such relation. Specifically, the report first describes the quantum defect theory focusing on its basic principle. The multi-channel quantum defect theory is then outlined centering on how to describe a Rydberg-type superexcited state. Description of a dissociative double-electron excited state is also discussed. The quantum defect theory is based on the fact that the physics of the motion of a Rydberg electron vary with the region in the electron's coordinate space. Finally, various molecular processes that involve a superexcited state are addressed focusing on autoionization, photoionization, dissociative recombination and bonding ionization of diatomic molecules. (N.K.)

  12. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

    Science.gov (United States)

    Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

    2014-04-01

    The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Atoms, molecules & elements

    CERN Document Server

    Graybill, George

    2007-01-01

    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  14. Photonic Molecule Lasers Revisited

    Science.gov (United States)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  15. Interstellar molecules and masers

    International Nuclear Information System (INIS)

    Nguyen-Q-Rieu; Guibert, J.

    1978-01-01

    The study of dense and dark clouds, in which hydrogen is mostly in molecular form, became possible since the discovery of interstellar molecules, emitting in the centimeter and millimeter wavelengths. The molecular lines are generally not in local thermal equilibrium (LTE). Their intensity can often be explained by invoking a population inversion mechanism. Maser emission lines due to OH, H 2 O and SiO molecules are among the most intense molecular lines. The H 2 CO molecule, detected in absorption in front of the cold cosmic background radiation of 2.7 K, illustrates the inverse phenomenon, the antimaser absorption. For a radio transition of frequency v, the inversion rate Δn (relative population difference between the upper and lower level) as well as the maser gain can be determined from the radio observations. In the case of the OH lines in the 2 PIsub(3/2), J=3/2 state, the inversion rates approximately 1 to 2% derived from the observations, are comparable with those obtained in the laboratory. The determination of the excitation mechanisms of the masers, through the statistical equilibrium and radiative transfer equations, implies the knowledge of collisional and radiative transition probabilities. A pumping model, which can satisfactorily explain the radio observations of some interstellar OH clouds, will be discussed [fr

  16. HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients

    DEFF Research Database (Denmark)

    Melsted, Wenna Nascimento; Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

    2017-01-01

    HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM...

  17. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

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

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds......,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia compounds....

  18. Lymphocytic subsets in occupationally exposed persons

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Wottawa, A.

    1989-04-01

    The percentage of CD2, CD4, CD8 and NK cells of peripheral blood was investigated in persons occupationally exposed to very low doses of ionizing radiation. Investigations were carried out by monoclonal antibodies and flow-cytometry. While significant effects of age and smoking habits on the relative number of CD8 cells and CD4/CD8 ratios could be established, no influence of the very low radiation exposure on the profile of lymphocytic cells in blood was found, except a very slight effect on the relative number of total T cells (= CD2 cells). 7tabs., 2figs., 16refs. (Author)

  19. Ibrutinib (PCI-32765) in chronic lymphocytic leukemia.

    Science.gov (United States)

    Jain, Nitin; O'Brien, Susan

    2013-08-01

    B-cell receptor (BCR) signaling is essential for chronic lymphocytic leukemia (CLL) cell survival. Many kinases in the BCR signaling pathway are being studied as potential therapeutic targets. Ibrutinib (PCI-32765) is a novel first-in-class selective inhibitor of Bruton tyrosine kinase. Preclinical evidence suggests that ibrutinib inhibits CLL cell survival and proliferation and affects CLL cell migration and homing. Early clinical data in patients with CLL and non-Hodgkin lymphoma is encouraging. It is likely that ibrutinib and other drugs targeting the BCR pathway will become an integral component of CLL therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. DNA repair in PHA stimulated human lymphocytes

    International Nuclear Information System (INIS)

    Catena, C.; Mattoni, A.

    1984-01-01

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

  1. Analysis in cytokinesis-blocked human lymphocytes

    International Nuclear Information System (INIS)

    Catena, C.; Mattoni, A.

    1987-01-01

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

  2. Brick mortar exposure and chronic lymphocytic leukemia.

    Science.gov (United States)

    Markovic-Denic, L; Jankovic, S; Marinkovic, J; Radovanovic, Z

    1995-01-01

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL.

  3. Brick mortar exposure and chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Markovic-Denic, Lj.; Jankovic, S.; Marinkovic, J.; Radovanovic, Z.

    1995-01-01

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author)

  4. Brick mortar exposure and chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Markovic-Denic, Lj; Jankovic, S [Institute of Epidemiology, Faculty of Medicine, Belgrade (Yugoslavia); Marinkovic, J [Institute of Social Medicine, Statistics and Healt Research, Faculty of Medicine, Belgrade (Yugoslavia); Radovanovic, Z [Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, 13110 Safat (Kuwait)

    1996-12-31

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author) 1 tab., 30 refs.

  5. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

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

    1991-01-01

    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage...... was significantly lower in the patients than in the control group (P less than 0.0001), whereas CD8+ and CD4/CD8 ratio figures did not differ significantly between patients and controls. The CD45RA+ counts were significantly higher in the patient group (P less than 0.01). The study supports previous investigations...

  6. Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.

    Science.gov (United States)

    Mokarizadeh, Aram; Delirezh, Nowruz; Morshedi, Ahhmad; Mosayebi, Ghasem; Farshid, Amir-Abbas; Dalir-Naghadeh, Bahram

    2012-01-01

    Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

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

    DEFF Research Database (Denmark)

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

    1977-01-01

    When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A...

  10. HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

    Science.gov (United States)

    Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

    2017-12-01

    The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

  11. A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

    OpenAIRE

    Bagnara, Davide; Kaufman, Matthew S.; Calissano, Carlo; Marsilio, Sonia; Patten, Piers E. M.; Simone, Rita; Chum, Philip; Yan, Xiao-Jie; Allen, Steven L.; Kolitz, Jonathan E.; Baskar, Sivasubramanian; Rader, Christoph; Mellstedt, Hakan; Rabbani, Hodjattallah; Lee, Annette

    2011-01-01

    Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activ...

  12. 1α,25(OH2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness.

    Directory of Open Access Journals (Sweden)

    Nitish Boodhoo

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

  13. Lymphocyte electrotaxis in vitro and in vivo.

    Science.gov (United States)

    Lin, Francis; Baldessari, Fabio; Gyenge, Christina Crenguta; Sato, Tohru; Chambers, Robert D; Santiago, Juan G; Butcher, Eugene C

    2008-08-15

    Electric fields are generated in vivo in a variety of physiologic and pathologic settings, including penetrating injury to epithelial barriers. An applied electric field with strength within the physiologic range can induce directional cell migration (i.e., electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils suggesting a potential role in cell positioning during wound healing. In the present study, we investigated the ability of lymphocytes to respond to applied direct current (DC) electric fields. Using a modified Transwell assay and a simple microfluidic device, we show that human PBLs migrate toward the cathode in physiologically relevant DC electric fields. Additionally, electrical stimulation activates intracellular kinase signaling pathways shared with chemotactic stimuli. Finally, video microscopic tracing of GFP-tagged immunocytes in the skin of mouse ears reveals that motile cutaneous T cells actively migrate toward the cathode of an applied DC electric field. Lymphocyte positioning within tissues can thus be manipulated by externally applied electric fields, and may be influenced by endogenous electrical potential gradients as well.

  14. Large granular lymphocytic leukaemia pathogenesis and management.

    Science.gov (United States)

    Dearden, Claire

    2011-02-01

    The WHO classification recognises three distinct disorders of large granular lymphocytes: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and agressive NK-cell leukaemia. Despite the different cell of origin, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK-cell leukaemia and the rare CD56(+) aggressive T-LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease. © 2010 Blackwell Publishing Ltd.

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

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N

    1987-01-01

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

  16. 1,4 Naphthoquinone protects radiation induced cell death and DNA damage in lymphocytes by activation Nrf2/are pathway and enhancing DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Nazir M; Sandur, Santosh K; Checker, Rahul; Sharma, Deepak; Poduval, T.B., E-mail: nazirbiotech@rediffmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai (India)

    2012-07-01

    1,4-Naphthoquinone (NQ) is the parent molecule of many clinically approved anticancer, anti-infective, and antiparasitic drugs such as anthracycline, mitomycin, daunorubicin, doxorubicin, diospyrin, and malarone. Presence of NQ during a-irradiation (4Gy) significantly reduced the death of irradiated murine splenic lymphocytes in a dose dependent manner (0.05-liM), with complete protection at liM as assessed by PI staining. Radioprotection by NQ was further confirmed by inhibition of caspase activation, decrease in cell size, DNA-fragmentation, nuclear-blebbing and clonogenic assay. All trans retinoic acid which is inhibitor of Nrf-2 pathway, completely abrogated the radioprotective effect of NQ, suggesting that radioprotective activity of NQ may be due to activation of Nrf-2 signaling pathways. Further, addition of NQ to lymphocytes activated Nrf-2 in time dependent manner as shown by confocal microscopy, electrophoretic mobility shift assay and quantitative real time PCR. It also increased the expression of Nrf-2 dependent cytoprotective genes like hemeoxygenase-1, MnSOD, catalse as demonstrated by real time PCR and flowcytometry. NQ protected lymphocytes significantly against radiation-induced cell death even when added after irradiation. Complete protection was observed by addition of NQ up to 2 h after irradiation. However, percentage protection decreased with increasing time interval. These results suggested that NQ may offer protection to lymphocytes activating repair pathways. Repair of radiation induced DNA strand breaks was studied by comet assay. Pretreatment of lymphocytes with NQ induced single strand breaks up to 6h but not double strand breaks in DNA. However, NQ mediated single strand breaks were repaired completely at longer time intervals. Addition of NQ to lymphocytes prior to 4 Gy a-radiation exposure showed decrease in the yield of DNA double strand breaks. The observed time-dependent decrease in the DNA strand breaks could be attributed to

  17. Quark chemistry: charmonium molecules

    International Nuclear Information System (INIS)

    De Rujula, A.; Jaffe, R.L.

    1977-01-01

    The theoretical and experimental evidence for two quark-two antiquark hadrons is reviewed. Concentration is placed on predictions for S-wave ''charmonium molecules,'' built of a c anti c charmonium pair and a light quark-antiquark pair. Their spectrum and quantum numbers are predicted and an estimate of their decay couplings and their prediction in monochromatic pion decays from charmonium resonances produced in e + e - -annihilation is given. Some S-wave charmonium resonances should be detectable in these decays, but typical branching ratios are only at the 1% level. 19 references

  18. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sezary syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Nickoloff, B.J.; Griffiths, E.M.; Baadsgaard, O.; Voorhees, J.J.; Hanson, C.A.; Cooper, K.D. (Univ. of Michigan Medical Center, Ann Arbor (USA))

    1989-04-21

    In mucosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mucosis fungoides (Sezary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. The authors discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sezary syndrome.

  19. Ultra-cold molecule production

    International Nuclear Information System (INIS)

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-01-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled

  20. Telomerase levels control the lifespan of human T lymphocytes

    NARCIS (Netherlands)

    Roth, Alexander; Yssel, Hans; Pene, Jerome; Chavez, Elizabeth A.; Schertzer, Mike; Lansdorp, Peter M.; Spits, Hergen; Luiten, Rosalie M.

    2003-01-01

    The loss of telomeric DNA with each cell division contributes to the limited replicative lifespan of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have previously shown that immortalization of human

  1. Apoptosis of lymphocytes in SLE: the level, correlation with ...

    African Journals Online (AJOL)

    Lymphocytes were isolated from venous blood by method of gradient centrifugation of all the blood through a Ficoll-pak solution. The quantity apoptotic cells was determined in leukocytes by flow cytometry Epics XL-2 (“Beckman Coulter”, USA). Analysis of lymphocyte subpopulations was carried by using two fluorescent ...

  2. 9 CFR 113.42 - Detection of lymphocytic choriomeningitis contamination.

    Science.gov (United States)

    2010-01-01

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

  3. Role of interferon in lymphocyte recruitment into the skin

    International Nuclear Information System (INIS)

    Issekutz, T.B.; Stoltz, J.M.; Webster, D.M.

    1986-01-01

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

  4. 21 CFR 864.8500 - Lymphocyte separation medium.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8500 Lymphocyte separation...

  5. Immunophenotypic enumeration of CD4 T-lymphocyte values in ...

    African Journals Online (AJOL)

    McRoy

    lymphocytes play a central role in regulation of immune response.[2] These ..... influence of sex hormones on lymphocyte subpopulations. ... Friedland GH. Early treatment for HIV-The Time. Has Come. N Engl J Med 1990;322:1000-1002. 7. Gebo KA, Gallant JE, Keruly JC, Moore RD. Absolute CD4 vs. CD4 percentage for ...

  6. The behavior of pig lymphocyte populations in vivo

    International Nuclear Information System (INIS)

    Binns, R.M.; Licence, S.T.; Pabst, R.

    1986-01-01

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

  7. Cytogenetical analysis in blood lymphocytes of cigarette smokers in ...

    African Journals Online (AJOL)

    Comet assay showed increased percentage of abnormalities in smokers (light, medium and heavy) than non-smokers. Conclusion: The frequencies of MN in buccal epithelial and blood lymphocytes are high in smokers; particularly heavy smoker group showed significantly increased results. Among them, the lymphocytic ...

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

    NARCIS (Netherlands)

    Gladkevich, A; Kauffman, HF; Korf, J

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

  9. Intestinal T lymphocytes of different rat strains in immunotoxicity

    NARCIS (Netherlands)

    Bruder, M.C.; Spanhaak, S.; Bruijntjes, J.P.; Michielsen, C.P.P.C.; Vos, J.G.; Kuper, C.F.

    1999-01-01

    In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes

  10. Activation of human T lymphocytes by Leishmania lipophosphoglycan

    DEFF Research Database (Denmark)

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

    1991-01-01

    This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......, the results suggest that human T lymphocytes can respond to glycolipid antigens....

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

    NARCIS (Netherlands)

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

    1997-01-01

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

  12. T gamma/delta lymphocytes in renal transplant recipients

    NARCIS (Netherlands)

    Raasveld, M. H.; Bloemena, E.; Surachno, S.; ten Berge, R. J.

    1992-01-01

    T gamma/delta lymphocytes are able to perform allospecific cytotoxicity and natural killer cytotoxicity in vitro. However, very little is known about their function in vivo. To investigate the possible involvement of T gamma/delta lymphocytes in the immune response to renal allografts, fine-needle

  13. Passing Current through Touching Molecules

    DEFF Research Database (Denmark)

    Schull, G.; Frederiksen, Thomas; Brandbyge, Mads

    2009-01-01

    The charge flow from a single C-60 molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two...

  14. Adhesion molecule profiles of B-cell non-Hodgkin's lymphomas in the leukemic phase

    Directory of Open Access Journals (Sweden)

    D.M. Matos

    2006-10-01

    Full Text Available We evaluated the expression of 10 adhesion molecules on peripheral blood tumor cells of 17 patients with chronic lymphocytic leukemia, 17 with mantle-cell lymphoma, and 13 with nodal or splenic marginal B-cell lymphoma, all in the leukemic phase and before the beginning of any therapy. The diagnosis of B-cell non-Hodgkin's lymphomas was based on cytological, histological, immunophenotypic, and molecular biology methods. The mean fluorescence intensity of the adhesion molecules in tumor cells was measured by flow cytometry of CD19-positive cells and differed amongst the types of lymphomas. Comparison of chronic lymphocytic leukemia and mantle-cell lymphoma showed that the former presented a higher expression of CD11c and CD49c, and a lower expression of CD11b and CD49d adhesion molecules. Comparison of chronic lymphocytic leukemia and marginal B-cell lymphoma showed that the former presented a higher expression of CD49c and a lower expression of CD11a, CD11b, CD18, CD49d, CD29, and CD54. Finally, comparison of mantle-cell lymphoma and marginal B-cell lymphoma showed that marginal B-cell lymphoma had a higher expression of CD11a, CD11c, CD18, CD29, and CD54. Thus, the CD49c/CD49d pair consistently demonstrated a distinct pattern of expression in chronic lymphocytic leukemia compared with mantle-cell lymphoma and marginal B-cell lymphoma, which could be helpful for the differential diagnosis. Moreover, the distinct profiles of adhesion molecules in these diseases may be responsible for their different capacities to invade the blood stream.

  15. MHC class II molecules and tumour immunotherapy

    International Nuclear Information System (INIS)

    Oven, I.

    2005-01-01

    Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

  16. Preparation of anti-CD4 monoclonal antibody-conjugated magnetic poly(glycidyl methacrylate) particles and their application on CD4+ lymphocyte separation.

    Science.gov (United States)

    Pimpha, Nuttaporn; Chaleawlert-umpon, Saowaluk; Chruewkamlow, Nuttapol; Kasinrerk, Watchara

    2011-03-15

    Novel immunomagnetic particles have been prepared for separation of CD4(+) lymphocytes. The magnetic nanoparticles with a diameter of approximately 5-6 nm were first synthesized by co-precipitation from ferrous and ferric iron solutions and subsequently encapsulated with poly(glycidyl methacrylate) (PGMA) by precipitation polymerization. Monoclonal antibody specific to CD4 molecules expressed on CD4(+) lymphocytes was conjugated to the surface of magnetic PGMA particles through covalent bonding between epoxide functional groups on the particle surface and primary amine groups of the antibodies. The generated immunomagnetic particles have successfully separated CD4(+) lymphocytes from whole blood with over 95% purity. The results indicated that these particles can be employed for cell separation and provide a strong potential to be applied in various biomedical applications including diagnosis, and monitoring of human diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Lymphocyte respiration in children with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Aburawi Elhadi H

    2012-12-01

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

  18. Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

    NARCIS (Netherlands)

    Kim, Christopher; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Purdue, Mark P; Huang, Wen-Yi; Liu, Chin-San; Cheng, Wen-Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J; Lim, Unhee; Hosgood, H Dean; Bonner, Matthew R; Caporaso, Neil E; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel

    BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication

  19. 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio

    NARCIS (Netherlands)

    Lin, Bochao Danae; Carnero-Montoro, Elena; Bell, Jordana T; Boomsma, Dorret I; de Geus, Eco J; Jansen, Rick; Kluft, Cornelis; Mangino, Massimo; Penninx, Brenda; Spector, Tim D; Willemsen, Gonneke; Hottenga, Jouke-Jan

    2017-01-01

    Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and

  20. FLT3 mutations in canine acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Suter, Steven E; Small, George W; Seiser, Eric L; Thomas, Rachael; Breen, Matthew; Richards, Kristy L

    2011-01-01

    FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations. We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting. The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations. These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias

  1. In vitro effect of the antimalarial drug proguanil hydrochloride on viability and DNA damage in human peripheral blood lymphocytes.

    Science.gov (United States)

    Gajski, Goran; Dinter, Domagoj; Garaj-Vrhovac, Vera

    2010-11-01

    This study aimed to evaluate the effect of proguanil, a chemical substance used for treatment and prevention of malaria on viability and DNA integrity in human lymphocytes in vitro. Two different concentrations of proguanil obtained from the plasma concentrations were used: 130ng/ml used for prophylactic treatment and 520ng/ml used in treatment of malaria. Testing was done with and without metabolic activation. Viability of lymphocytes decreased in time and dose dependent manner. Comet assay parameters showed similar effects, indicating that some damage to DNA molecule can occur. Frequency of sister chromatid exchanges did not show significant deviation from the control samples. As for the proliferation kinetics no significant changes were noticed. Since majority of DNA damaging effect is induced after metabolic activation it is to be concluded that activity of proguanil is dependent upon the active metabolite cycloguanil and that monitoring should be conducted especially among frequent travellers. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...... T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied...... by a decrease in the number of activated T cells expressing Ia antigens. On the other hand, IFN MLRs contained greater numbers of cells expressing the T10 differentiation antigen. In experiments with purified T-cell subsets the IFN effect was exerted directly on the T4 cells and not mediated by either T8...

  3. Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction.

    Science.gov (United States)

    Ginés, Silvia; Mariño, Marta; Mallol, Josefa; Canela, Enric I; Morimoto, Chikao; Callebaut, Christian; Hovanessian, Ara; Casadó, Vicent; Lluis, Carmen; Franco, Rafael

    2002-01-01

    The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell-surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA-CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA-binding site or with exogenous ADA resulted in a significant reduction (50-70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA-CD26 interaction in the lymphocyte-epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA-CD26 interaction in cell-to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA-CD26 interaction on the cell surface has a role in lymphocyte-epithelial cell adhesion. PMID

  4. Minimal residual disease in chronic lymphocytic leukaemia.

    Science.gov (United States)

    García Vela, José Antonio; García Marco, José Antonio

    2018-02-23

    Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy. In this review, we discuss the different MRD methods of analysis, which source of tumour samples must be analysed, the future role of the detection of circulating tumour DNA, and the potential role of MRD negativity in clinical practice in the modern era of CLL therapy. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  5. Lymphocytic nucleolar index in the combined application

    Energy Technology Data Exchange (ETDEWEB)

    Kilyovska, M.; Nechev, Kh.; Vankova, P.; Tsvetkov, P.; Shopova, V. (Meditsinski Fakultet, Pleven (Bulgaria). Katedra Mediko-Sanitarna Zashtita)

    1982-01-01

    Sex mature male rats were irradiated with 5,25 and 50 rad from X-ray source. One group of irradiated animals was treated intraperitoneally with 10 mCi/animal Ce/sup 144/ or 0.04 mCi/g Sr/sup 89/. The second group was treated only with radionuclide. The nucleolar index (NI) of the lymphocytes in a blood smear was studied on the 1st, 3rd, 8th and 30th day after application. It was found that X-irradiation increased the value of NI after the 15th day, the effect being independent on the dose rates. Ce/sup 144/, applied alone in combination with external irradiation, also causes an increase of NI. Combined application of Sr/sup 89/ and external irradiation leads after one month to a decrease of NI. The results are discussed in connection with radionuclide kinetics and dose distribution.

  6. Predictive radiosensitivity tests in human lymphocytes

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  7. Sudden unexpected death associated with lymphocytic thyroiditis

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... 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...

  8. [Lymphocyte metabolism in children with extensive burns].

    Science.gov (United States)

    Artem'ev, S A; Nazarov, I P; Kamzalakova, N I; Bulygin, G V

    2009-01-01

    The results of the study lead to the conclusion that the development of burn disease in children is accompanied by significant lymphocytic structural metabolic changes that determine the functional capabilities of cells and the immune system as a whole. There is an evident activation of the glutathione antioxidant system, a drastic activation of enzymes that ensure Krebs cycle reactions, as well as activation of anaerobic processes. The above changes are mainly caused by the activated sympathoadrenal system that is characteristic of stresses. The knowledge about the metabolic mechanisms responsible for the development of cellular reactions to burn shock and burn disease permits specification of the elements of the pathogenesis of these severe conditions and substantiation of the possibility of using metabolic correction in the complex treatment of children with the above pathology.

  9. Lanthanide single molecule magnets

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

    2015-10-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

  10. Lanthanide single molecule magnets

    CERN Document Server

    Tang, Jinkui

    2015-01-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  11. Molecules in the Spotlight

    Energy Technology Data Exchange (ETDEWEB)

    Cryan, James

    2010-01-26

    SLAC has just unveiled the world's first X-ray laser, the LCLS. This machine produces pulses of X-rays that are ten billion times brighter than those from conventional sources. One of the goals of this machine is to make movies of chemical reactions, including reactions necessary for life and reactions that might power new energy technologies. This public lecture will show the first results from the LCLS. As a first target, we have chosen nitrogen gas, the main component of the air we breathe. Using the unprecedented power of the LCLS X-rays as a blasting torch, we have created new forms of this molecule and with unique electronic arrangements. Please share with us the first insights from this new technology.

  12. Magnetic field modification of ultracold molecule-molecule collisions

    International Nuclear Information System (INIS)

    Tscherbul, T V; Suleimanov, Yu V; Aquilanti, V; Krems, R V

    2009-01-01

    We present an accurate quantum mechanical study of molecule-molecule collisions in the presence of a magnetic field. The work focuses on the analysis of elastic scattering and spin relaxation in collisions of O 2 ( 3 Σ g - ) molecules at cold (∼0.1 K) and ultracold (∼10 -6 K) temperatures. Our calculations show that magnetic spin relaxation in molecule-molecule collisions is extremely efficient except at magnetic fields below 1 mT. The rate constant for spin relaxation at T=0.1 K and a magnetic field of 0.1 T is found to be as large as 6.1x10 -11 cm -3 s -1 . The magnetic field dependence of elastic and inelastic scattering cross sections at ultracold temperatures is dominated by a manifold of Feshbach resonances with the density of ∼100 resonances per Tesla for collisions of molecules in the absolute ground state. This suggests that the scattering length of ultracold molecules in the absolute ground state can be effectively tuned in a very wide range of magnetic fields. Our calculations demonstrate that the number and properties of the magnetic Feshbach resonances are dramatically different for molecules in the absolute ground and excited spin states. The density of Feshbach resonances for molecule-molecule scattering in the low-field-seeking Zeeman state is reduced by a factor of 10.

  13. Ibrutinib: A Review in Chronic Lymphocytic Leukaemia.

    Science.gov (United States)

    Deeks, Emma D

    2017-02-01

    Ibrutinib (Imbruvica ® ) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE). Likewise, a combination of ibrutinib, bendamustine and rituximab was more effective in previously-treated adults than bendamustine plus rituximab in a phase III placebo-controlled study (HELIOS). These ibrutinib regimens were associated with significantly better progression-free survival, overall response rates, and overall survival than the comparators (in protocol-specified or planned analyses), with ibrutinib therapy providing benefit regardless of adverse prognostic factors, such as del(17p)/TP53 mutation and del(11q). Ibrutinib has an acceptable tolerability profile, although certain adverse events (e.g. bleeding and atrial fibrillation) require consideration. Redistribution lymphocytosis can occur, but is not indicative of disease progression. Although longer-term data would be beneficial, ibrutinib is a welcome treatment option for patients with CLL, including those who have higher-risk disease or are less physically fit. Indeed, current EU and US guidelines recommend/prefer the drug for the first- and/or subsequent-line treatment of certain patients, including those with del(17p)/TP53 mutation.

  14. Radioprotective effect of flavonoid quercetin on human lymphocytic cells; Efeito radioprotetor do flavonóide quercetina sobre células linfocitárias humanas

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Williams N.; Melo, Larissa S.A.; Lima, Maíra V.; Luna Filho, Ricardo L.C.; Melo, Ana M.M.A.; Silva, Edvane B., E-mail: williams.wns@gmail.com, E-mail: larissamelo.pe@gmail.com, E-mail: mairavasconceloslima@gmail.com, E-mail: ricardolclf@hotmail.com, E-mail: amdemelo@hotmail.com, E-mail: edvborges@yahoo.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil)

    2017-07-01

    Several substances of synthetic and natural origin have been studied in relation to their ability to protect the body from damage caused by ionizing radiation. Among these substances, quercetin has been shown to be a molecule of natural origin with high radioprotective potential due to its antioxidant properties. The objective of this study was to determine, in vitro, the radioprotective effect of quercetin on human lymphocytes exposed to gamma radiation. Blood was irradiated at the 2.5, 3.5 and 4.5 Gy doses and then lymphocyte culture with quercetin at preselected concentrations of 37.5 and 75 μM. Subsequently, slides were prepared for analysis and quantification of the metaphases present in lymphocyte cells. The results demonstrated that irradiated lymphocytes and later exposed to quercetin presented a lower number of chromosomal alterations compared to the control group which was irradiated and not exposed to quercetin. Therefore, the results suggest a radioprotective effect of flavonoid quercetin on human lymphocytes exposed, in vitro, to ionizing radiation.

  15. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

    International Nuclear Information System (INIS)

    Gajski, Goran; Garaj-Vrhovac, Vera; Orescanin, Visnja

    2008-01-01

    To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell

  16. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Gajski, Goran [Institute for Medical Research and Occupational Health, Mutagenesis Unit, 10000 Zagreb (Croatia); Garaj-Vrhovac, Vera [Institute for Medical Research and Occupational Health, Mutagenesis Unit, 10000 Zagreb (Croatia); Orescanin, Visnja [Ruder Boskovic Institute, 10000 Zagreb (Croatia)

    2008-08-15

    To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.

  17. Effect of postirradiation anoxia on radiosensitivity of lymphocytes

    International Nuclear Information System (INIS)

    Schrek, R.

    1976-01-01

    Radiosensitivity was measured by viable-lymphocyte counts and by uridine uptake. The viability of the lymphocytes was based on morphologic characteristics visualized by phase contrast microscopy of the cells in a special slide chamber. Low doses of x rays (10 to 1000 R) and incubation at 37 0 C killed lymphocytes in interphase with the production of pyknotic nuclei (nuclear death), and large doses (6000 R) produced nuclei with clear nucleoplasm (cytoplasmic death). Nuclear, but not cytoplasmic, death was inhibited by incubation of the irradiated cells at 27 0 C. Postirradiation anoxia had no effect on development of the nuclear and cytoplasmic death of lymphocytes irradiated with 100 to 6000 R. Anoxia had no effect on the early response of lymphocytes to phytohemagglutinin (PHA) [increase in ribonucleic acid (RNA) and protein synthesis] but inhibited completely the late effects [increase in deoxyribonucleic acid (DNA) synthesis and transformation into lymphoblastoid cells]. The PHA caused relative radioresistance of lymphocytes under aerobic conditions and, to a lesser extent, under anaerobic conditions. The slight radioresistance induced by PHA in anoxic lymphocytes apparently did not depend on an increase in DNA synthesis or on the transformation to lymphoblastoid cells

  18. Electron-excited molecule interactions

    International Nuclear Information System (INIS)

    Christophorou, L.G.; Tennessee Univ., Knoxville, TN

    1991-01-01

    In this paper the limited but significant knowledge to date on electron scattering from vibrationally/rotationally excited molecules and electron scattering from and electron impact ionization of electronically excited molecules is briefly summarized and discussed. The profound effects of the internal energy content of a molecule on its electron attachment properties are highlighted focusing in particular on electron attachment to vibrationally/rotationally and to electronically excited molecules. The limited knowledge to date on electron-excited molecule interactions clearly shows that the cross sections for certain electron-molecule collision processes can be very different from those involving ground state molecules. For example, optically enhanced electron attachment studies have shown that electron attachment to electronically excited molecules can occur with cross sections 10 6 to 10 7 times larger compared to ground state molecules. The study of electron-excited molecule interactions offers many experimental and theoretical challenges and opportunities and is both of fundamental and technological significance. 54 refs., 15 figs

  19. Organic Molecules in Meteorites

    Science.gov (United States)

    Martins, Zita

    2015-08-01

    Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (meteorites contain soluble organic molecules with different abundances and distributions, which may reflect the extension of aqueous alteration or thermal metamorphism on the meteorite parent bodies. Extensive aqueous alteration on the meteorite parent body may result on 1) the decomposition of α-amino acids [5, 6]; 2) synthesis of β- and γ-amino acids [2, 6-9]; 3) higher relative abundances of alkylated polycyclic aromatic hydrocarbons (PAHs) [6, 10]; and 4) higher L-enantiomer excess (Lee) value of isovaline [6, 11, 12].The soluble organic content of carbonaceous meteorites may also have a contribution from Fischer-Tropsch/Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10] Elsila et al. (2005) GCA 5, 1349. [11] Glavin and Dworkin (2009) PNAS 106, 5487. [12] Pizzarello et al. (2003) GCA 67, 1589. [13] Chan et al. (2012) MAPS. 47, 1502

  20. Assessment of in vitro radiosensitivity of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Knox, S.J.; Shifrine, M.; Rosenblatt, L.S.

    1980-01-01

    The proliferative capacity of sensitive lymphocyte progenitor cells, from thirty-one clinically normal adults, was evaluated following in vitro x-irradiation (0-400R). Radiation effects were studied using both whole blood and lymphocyte-enriched mononuclear cell fractions in the lymphocyte stimulation test and colony formation assay with 6 different mitogens and antigens. Radiation dose-response survival curves were determined for the different test groups. The sensitivity of the different assay systems is compared and normative values are presented that may be used for comparison purposes to determine the relative radiosensitivity of atypical individuals and groups of individuals

  1. Lymphocyte mediators of delayed hypersensitivity; the early phase cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefford, M J; McGregor, D D [Trudeau Inst., Saranac Lake, N.Y. (USA)

    1978-04-01

    Inbred rats were immunized with living Bacillus Calmette-Guerin (BCG) and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen, and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated /sup 3/HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

  2. Tunnelling of a molecule

    International Nuclear Information System (INIS)

    Jarvis, P.D.; Bulte, D.P.

    1998-01-01

    A quantum-mechanical description of tunnelling is presented for a one-dimensional system with internal oscillator degrees of freedom. The 'charged diatomic molecule' is frustrated on encountering a barrier potential by its centre of charge not being coincident with its centre of mass, resulting in transitions amongst internal states. In an adiabatic limit, the tunnelling of semiclassical coherent-like oscillator states is shown to exhibit the Hartman and Bueuttiker-Landauer times t H and t BL , with the time dependence of the coherent state parameter for the tunnelled state given by α(t) = α e -iω(t+Δt) , Δt = t H - it BL . A perturbation formalism is developed, whereby the exact transfer matrix can be expanded to any desired accuracy in a suitable limit. An 'intrinsic' time, based on the oscillator transition rate during tunnelling, transmission or reflection, is introduced. In simple situations the resulting intrinsic tunnelling time is shown to vanish to lowest order. In the general case a particular (nonzero) parametrisation is inferred, and its properties discussed in comparison with the literature on tunnelling times for both wavepackets and internal clocks. Copyright (1998) CSIRO Australia

  3. Single molecule tracking

    Science.gov (United States)

    Shera, E. Brooks

    1988-01-01

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photones are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions.

  4. Theoretical Investigations Regarding Single Molecules

    DEFF Research Database (Denmark)

    Pedersen, Kim Georg Lind

    Neoclassical Valence Bond Theory, Quantum Transport, Quantum Interference, Kondo Effect, and Electron Pumping. Trap a single organic molecule between two electrodes and apply a bias voltage across this "molecular junction". When electrons pass through the molecule, the different electron paths can...... interfere destructively or constructively. Destructive interference effects in electron transport could potentially improve thermo-electrics, organic logic circuits and energy harvesting. We have investigated destructive interference in off-resonant transport through organic molecules, and have found a set...

  5. Biofuels: from microbes to molecules

    National Research Council Canada - National Science Library

    Lu, Xuefeng

    2014-01-01

    .... The production of different biofuel molecules including hydrogen, methane, ethanol, butanol, higher chain alcohols, isoprenoids and fatty acid derivatives, from genetically engineered microbes...

  6. Labelled molecules, modern research implements

    International Nuclear Information System (INIS)

    Pichat, L.; Langourieux, Y.

    1974-01-01

    Details of the synthesis of carbon 14- and tritium-labelled molecules are examined. Although the methods used are those of classical organic chemistry the preparation of carbon 14-labelled molecules differs in some respects, most noticeably in the use of 14 CO 2 which requires very special handling techniques. For the tritium labelling of organic molecules the methods are somewhat different, very often involving exchange reactions. The following are described in turn: the so-called Wilzbach exchange method; exchange by catalysis in solution; catalytic hydrogenation with tritium; reductions with borotritides. Some applications of labelled molecules in organic chemistry, biochemistry and pharmacology are listed [fr

  7. AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

    Science.gov (United States)

    Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

    2010-02-01

    The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor

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

    International Nuclear Information System (INIS)

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

    1980-01-01

    In vitro radiation-survival of peripheral blood T-lymphocytes was studied in fifteen clinically normal adults and four patients with Fanconi's anemia (FA). Lymphocyte blastogenesis and cloning were measured following phytohemagglutinin (PHA) or Concanavalin-A (Con-A) stimulation. PHA-responsive lymphocytes from FA patients were significantly more radiosensitive than lymphocytes from normal individuals

  9. Separation and properties of EA-rosette-forming lymphocytes in humans

    NARCIS (Netherlands)

    van Oers, M. H.; Zeijlemaker, W. P.; Schellekens, P. T.

    1977-01-01

    Human peripheral blood lymphocytes were separated into subpopulations enriched or depleted with respect to B lymphocytes (Ig-bearing cells), T lymphocytes, (cell forming rosettes with sheep erythrocytes: E-RFC) and Fc receptor-bearing lymphocytes (EA-RFC). From the distributions and recoveries of

  10. Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human melanoma in vitro model: studying immunogenic cell death, dendritic cell maturation and interaction with cytotoxic T lymphocytes

    Directory of Open Access Journals (Sweden)

    Heinrich B

    2017-05-01

    Full Text Available B Heinrich,1 J Klein,1 M Delic,1 K Goepfert,1 V Engel,1 L Geberzahn,1 M Lusky,2 P Erbs,2 X Preville,3 M Moehler1 1First Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany; 2Transgene SA, Illkirch-Graffenstaden, 3Amoneta Diagnostics, Huningue, France Abstract: Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF or transforming 5-fluorocytosine (5-FC into 5-fluorouracil (5-FU. We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on human immune cells, specifically regarding the activation of dendritic cells (DCs and the interaction with the autologous cytotoxic T lymphocyte (CTL clone, was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone or in combination with 5-FC and 5-FU. The influence of viral infection on cell viability followed a time- and multiplicity of infection dependent manner. Combination of virus treatment with 5-FU resulted in stronger reduction of cell viability. TG6002 in combination with 5-FC did not significantly strengthen the reduction of cell viability in this setting. Expression of calreticulin and high mobility group 1 protein (HMGB1, markers of immunogenic cell death (ICD, could be detected after viral infection. Accordingly, DC maturation was noted after viral oncolysis. DCs presented stronger expression of activation and maturation markers. The autologous CTL clone IVSB expressed the activation marker CD69, but viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia viruses JX-GFP and TG6002 lyse

  11. Growing interstellar molecules with ion-molecule reactions

    International Nuclear Information System (INIS)

    Bohme, D.K.

    1989-01-01

    Laboratory measurements of gas-phase ion-molecule reactions continue to provide important insights into the chemistry of molecular growth in interstellar environments. It is also true that the measurements are becoming more demanding as larger molecules capture our interest. While some of these measurements are motivated by current developments in chemical models of interstellar environments or by new molecular observations by astronomers, others explore novel chemistry which can lead to predictions of new interstellar molecules. Here the author views the results of some recent measurements, taken in the Ion Chemistry Laboratory at York University with the SIFT technique, which address some of the current needs of modellers and observers and which also provide some new fundamental insight into molecular growth, particularly when it occurs in the presence of large molecules such as PAH molecules which are now thought to have a major influence on the chemistry of interstellar environments in which they are present

  12. The Genotoxicity of Sodium Arsenite in Human Lymphocyte Culture

    International Nuclear Information System (INIS)

    El-Habit Ola, H.M.

    1998-01-01

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

  13. Chronic Lymphocytic Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Chronic lymphocytic leukemia (CLL) treatment options can include observation, steroids, chemotherapy, targeted therapy, and/or stem cell transplant. Get detailed information about newly diagnosed and recurrent CLL and available treatment modalities in this summary for clinicians.

  14. The genotoxicity of sodium arsenite in human lymphocyte culture

    International Nuclear Information System (INIS)

    Elhabit, O.H.M.

    1995-01-01

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

  15. Response of human lymphocytes to low gamma ray doses

    International Nuclear Information System (INIS)

    Vega Carrillo, HR; Banuelos Valenzuela, R; Manzanares Acuna, E; Sanchez-Rodriguez, S.H

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...... mucosal specimens. Intraepithelial CD1-positive dendritic cells were found in all specimens. However, there was no difference between the number of these Langerhans cells found in the study group and the number found in the controls. In every specimen the intraepithelial lymphocyte population...... was dominated by T lymphocytes, and there were relatively few B cells. Similarly the ratio between CD4- and CD8-positive lymphocytes in the study group and the controls was the same. In all specimens there was a dominance of T suppressor/cytotoxic cells compared with T helper/inducer cells. The study confirms...

  17. Recognition of lyso-phospholipids by human natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Lisa M Fox

    2009-10-01

    Full Text Available Natural killer T (NKT cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC. Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

  18. Cloning and Sequencing of Protein Kinase cDNA from Harbor Seal (Phoca vitulina Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jennifer C. C. Neale

    2004-01-01

    Full Text Available Protein kinases (PKs play critical roles in signal transduction and activation of lymphocytes. The identification of PK genes provides a tool for understanding mechanisms of immunotoxic xenobiotics. As part of a larger study investigating persistent organic pollutants in the harbor seal and their possible immunomodulatory actions, we sequenced harbor seal cDNA fragments encoding PKs. The procedure, using degenerate primers based on conserved motifs of human protein tyrosine kinases (PTKs, successfully amplified nine phocid PK gene fragments with high homology to human and rodent orthologs. We identified eight PTKs and one dual (serine/threonine and tyrosine kinase. Among these were several PKs important in early signaling events through the B- and T-cell receptors (FYN, LYN, ITK and SYK and a MAP kinase involved in downstream signal transduction. V-FGR, RET and DDR2 were also expressed. Sequential activation of protein kinases ultimately induces gene transcription leading to the proliferation and differentiation of lymphocytes critical to adaptive immunity. PKs are potential targets of bioactive xenobiotics, including persistent organic pollutants of the marine environment; characterization of these molecules in the harbor seal provides a foundation for further research illuminating mechanisms of action of contaminants speculated to contribute to large-scale die-offs of marine mammals via immunosuppression.

  19. T Lymphocyte-Endothelial Interactions: Emerging Understanding of Trafficking and Antigen-Specific Immunity

    Directory of Open Access Journals (Sweden)

    Christopher Vincent Carman

    2015-11-01

    Full Text Available Antigen-specific immunity requires regulated trafficking of T cells in and out of diverse tissues in order to orchestrate lymphocyte development, immune surveillance, responses and memory. The endothelium serves as a unique barrier, as well as a sentinel, between the blood and the tissues and as such it plays an essential locally tuned role in regulating T cell migration and information exchange. While it is well established that chemoattractants and adhesion molecules are major determinants of T cell trafficking, emerging studies have now enumerated a large number of molecular players as well as a range of discrete cellular remodeling activities (e.g. transmigratory cups and invadosome-like protrusions, IPLs that participate in directed migration and pathfinding by T cells. In addition to providing trafficking cues, intimate cell-cell interaction between lymphocytes and endothelial cells provide instruction to T cells that influence their activation and differentiation states. Perhaps the most intriguing and underappreciated of these ‘sentinel’ roles is the ability of the endothelium to act as a non-hematopoietic ‘semi-professional’ antigen-presenting cell. Close contacts between circulating T cells and antigen-presenting endothelium may play unique non-redundant roles in shaping adaptive immune responses within the periphery. A better understanding of the mechanisms directing T cell trafficking and the antigen-presenting role of the endothelium may not only increase our knowledge of the adaptive immune response but also empower the utility of emerging immunomodulatory therapeutics.

  20. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

    Science.gov (United States)

    Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

    2018-06-08

    The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

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

  2. Cytogenetic investigations of chronic lymphocytic leukemia.

    Science.gov (United States)

    Wren, Catherine; Moriarty, Helen; Marsden, Katherine; Tegg, Elizabeth

    2010-04-15

    This study aimed to determine which culture method would yield the highest culture success rate, mitotic index, banding resolution, and abnormality rate in investigation of patients with chronic lymphocytic leukemia (CLL). A range of culture techniques for conventional cytogenetic (CC) analyses was compared: 24-hour unstimulated, 72 hours incubation with additional fetal calf serum, 72 hours stimulation with interleukin 4, 72 hours stimulation with lipopolysaccharide (LPS), 72 hours stimulation with TPA (12-O-tetradecanoylphorbol 13-acetate), and 72 hours stimulation with CpG-oligonucleotide DSP30 + Interleukin-2 (IL-2). CC abnormality rates were also compared to fluorescence in situ hybridization (FISH) results using probes for CLL (LSI D13S319/13q34/CEP 12: LSI ATM/p53). Forty-five samples from 24 patients (consisting of 11 newly diagnosed and 13 previously diagnosed patients) were included. For CC, a 100.0% culture success rate was achieved (n = 45) by means of an EDTA (ethylenediaminetetraacetic acid) peripheral blood sample with an associated 62.5% CC abnormality rate (n = 24). FISH detected an abnormality rate of 75.0% (n = 24). The combined CC and FISH abnormality rate was 87.5% (n = 24). This study demonstrates that CC that uses TPA and DSP30 + IL-2 on EDTA peripheral blood is effective in the investigation of CLL and may be used as a supplement to FISH studies. Copyright 2010 Elsevier Inc. All rights reserved.

  3. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  4. Therapeutic advancement of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lu Kang

    2012-09-01

    Full Text Available Abstract Despite the combinations of chemotherapy with monoclonal antibodies have further improved response rates, chronic lymphocytic leukemia (CLL remains an incurable disease with an extremely variable course. This article reviews the ongoing clinical advances in the treatment of CLL in both previously untreated and relapsed disease and focuses on the benefit of different therapeutic strategies, the most effective therapy combinations and the potential activity of novel agents. Novel agents and combination therapies have been investigated by several studies in both the upfront and relapsed setting, particularly for patients with 17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents and combination therapies have improved initial response rates, ongoing studies are continued to determine and improve the efficacy and safety. Despite advancements in the treatment of CLL have led to high response rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT remains the only curative option and reduced-intensity conditioning (RIC allo-HSCT must be strongly considered whenever feasible. As such, ongoing studies of these agents and other novel approaches in clinical development are needed to expand and improve treatment options for CLL patients.

  5. Autoreactive lymphocytes in thyroid disorders. 2

    International Nuclear Information System (INIS)

    Petersen, J.; Feldt-Rasmussen, U.; Siersbaek-Nielsen, K.; Hoeier-Madsen, M.; Larsen, F.; Husby, S.

    1986-01-01

    Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radioimmune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 x 10 6 /ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion. (author)

  6. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increase...... to large particulate antigens; the response to small antigens was not affected. The mode of action of chloroquine and the possible consequences of the findings for dosage of chloroquine when used for malaria prophylaxis is discussed.......The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increased...... the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  7. Chronic lymphocytic leukaemia: An immunobiology approach

    Directory of Open Access Journals (Sweden)

    Kostareli Efterpi

    2008-01-01

    Full Text Available B cell chronic lymphocytic leukaemia (CLL is the most common adult leukaemia that follows an extremely variable clinical course. Several important prognostic parameters defining pathogenic and clinical subgroups of CLL have been identified and validated recently. The biological significance of immunoglobulin (Ig heavy chain variable region gene (IgHV mutational status and associated ZAP-70 over-expression, CD38 and chromosomal aberrations have enabled to identify patients at high risk for early disease progression and inferior survival. Moreover, studies of the B cell antigen receptor (BCR structure and receptor signaling have been most helpful in revealing some new aspects of the biology of this disease. In particular, the analysis of IG genes has revealed that the expressed IgHV/IgKV/IgLV gene repertoires of CLL cells differ from those of normal B cells. A further unique feature of the CLL IG repertoire is the existence of subsets of cases with "stereotyped" BCRs. Accumulating molecular and phenotypic data support the notion that CLL development and evolution is not a simple scholastic event and strongly indicates a role for antigen in driving the cell of origin for at least some subsets of CLL cases.

  8. Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

    DEFF Research Database (Denmark)

    Langhoff, E; Ladefoged, J; Ødum, Niels

    1986-01-01

    The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD......). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte...... responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte...

  9. Cell proliferation and radiosensitivity of cow lymphocytes in culture

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  10. Latent childhood thyroid carcinoma in diffuse lymphocytic thyroiditis.

    Science.gov (United States)

    Siegal, A; Mimouni, M; Kovalivker, M; Griffel, B

    1983-07-01

    Diffuse thyroid enlargement in a child is a rare presenting symptom of thyroid carcinoma. A papillary carcinoma may be hidden in a diffuse lymphocytic thyroiditis and should be carefully searched for during surgery. Furthermore, the finding, in frozen sections, of psammoma bodies in a lymphocytic thyroiditis should raise the suspicion of an occult malignant neoplasm. A case illustrating these diagnostic difficulties in a 5-year-old child is presented.

  11. Bare lymphocyte syndrome: imaging findings in an adult

    International Nuclear Information System (INIS)

    Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M.; Lambert, J.; De Clerck, L.S.

    2001-01-01

    Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

  12. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-01-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  13. Analysis of cytotoxic effects of nickel on human blood lymphocytes.

    Science.gov (United States)

    Zarei, Mohammad Hadi; Hosseini Shirazi, Seyed Farshad; Aghvami, Marjan; Salimi, Ahmad; Pourahmad, Jalal

    2018-02-01

    Nickel compounds possess many applications in different industrial processes. Human beings are exposed to nickel commonly through occupational exposure and food. Although a few studies so far have investigated the effects of nickel compounds on human lymphocytes, the complete mechanism of cytotoxicity of this metal on human lymphocytes is yet to be determined. The intention of this paper was to determine the cytotoxicity mechanism of water soluble NiCl 2 toward human lymphocytes using the accelerated cytotoxicity mechanisms screening (ACMS) technique. Human lymphocytes were isolated from the blood of healthy subjects based on Ficoll-Paque PLUS standard method. For the assessment of cell viability, lymphocytes were incubated with 0.05-1 mM NiCl 2 for 12 h. Determination of mechanistic parameters was performed 2, 4 and 6 h after treatment of cells with ½ EC50 12h , EC50 12h and 2EC50 12h of NiCl 2 . Our results demonstrate that cytotoxicity of NiCl 2 on human lymphocytes is associated with increased ROS formation, mitochondrial membrane potential collapse, glutathione depletion, lysosomal membrane damage, cellular proteolysis and activation of caspase-3 before cytotoxicity ensued.

  14. Mechanism of chlorphentermine-induced lymphocyte toxicity: initial investigations

    International Nuclear Information System (INIS)

    Sauers, L.J.; Wierda, D.; Reasor, M.J.

    1986-01-01

    Chlorphentermine (CP) inhibits the blastogenic response of mouse splenic and human peripheral blood lymphocytes to the T-cell mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A). The purpose of these studies was to examine in vitro the mechanism mediating this immunosuppression. If mouse or human lymphocytes are pretreated with CP for 30 minutes, then stimulated with PHA, their blastogenic response is inhibited 80% and 45%, respectively. However, if CP is not added until 10 minutes or later following PHA stimulation, the inhibitory effect of the drug is essentially eliminated. The authors also determined that CP can potentiate Con A-induced agglutination of human lymphocytes. Enhanced agglutination can result from changes in the integrity of membrane phospholipids. Because changes in membrane phospholipid biochemistry characteristically occur within 10 minutes after mitogen-induced lymphocyte activation, the authors examined whether CP altered the incorporation of choline into cellular phospholipids. They found that CP decreases overall incorporation of 14 C-choline into cellular phospholipids of mouse lymphocytes by 45% during the first 4 hours of activation. These data suggest that the immunotoxicity associated with CP may be mediated by drug-induced changes at the membrane level that appear to occur early during lymphocyte activation

  15. Identification of CD3+ T lymphocytes in the green turtle Chelonia mydas

    Science.gov (United States)

    Munoz, F.A.; Estrada-Parra, S.; Romero-Rojas, A.; Work, Thierry M.; Gonzalez-Ballesteros, E.; Estrada-Garcia, I.

    2009-01-01

    To understand the role of the immune system with respect to disease in reptiles, there is the need to develop tools to assess the host's immune response. An important tool is the development of molecular markers to identify immune cells, and these are limited for reptiles. We developed a technique for the cryopreservation of peripheral blood mononuclear cells and showed that a commercially available anti-CD3 epsilon chain antibody detects a subpopulation of CD3 positive peripheral blood lymphocytes in the marine turtle Chelonia mydas. In the thymus and in skin inoculated with phytohemagglutinin, the same antibody showed the classical staining pattern observed in mammals and birds. For Western blot, the anti-CD3 antibodies identified a 17.6 kDa band in membrane proteins of peripheral blood mononuclear cell compatible in weight to previously described CD3 molecules. This is the first demostration of CD3+ cells in reptiles using specific antibodies.

  16. Cutaneous Mucormycosis Following a Bullous Pemphigoid Flare in a Chronic Lymphocytic Leukemia Patient on Ibrutinib.

    Science.gov (United States)

    Stein, Matthew K; Karri, Saradasri; Reynolds, Jackson; Owsley, Jeff; Wise, Austin; Martin, Mike G; Zare, Fereshteh

    2018-04-01

    While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection. Consistent with a growing evidence of literature identifying opportunistic fungal infections in patients on ibrutinib therapy, providers should be cognizant of medical comorbidities that may predispose to such infections and explore methods of prevention before starting ibrutinib and other SMKIs.

  17. Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

    Directory of Open Access Journals (Sweden)

    Shigeo Koido

    2010-01-01

    Full Text Available The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs that can reduce the tumor mass. Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

  18. Tuberculin purified protein derivative-reactive T cells in cord blood lymphocytes.

    OpenAIRE

    Shiratsuchi, H; Tsuyuguchi, I

    1981-01-01

    Lymphocytes obtained from cord blood of newborn babies who were born of healthy mothers were studied in vitro for their responsiveness to purified protein derivative (PPD) of tuberculin. Cord blood lymphocytes proliferated in vitro by stimulation with PPD, despite wide variations in the results. Studies with fractionated lymphocytes revealed that PPD-responding cells belonged to E-rosetting, nylon wool-nonadherent T lymphocytes. Non-E-rosetting B lymphocytes alone did not proliferate at all a...

  19. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review.

    Science.gov (United States)

    Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

    2017-10-01

    Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

  20. Enzyme Molecules in Solitary Confinement

    Directory of Open Access Journals (Sweden)

    Raphaela B. Liebherr

    2014-09-01

    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  1. Organizing and addressing magnetic molecules.

    Science.gov (United States)

    Gatteschi, Dante; Cornia, Andrea; Mannini, Matteo; Sessoli, Roberta

    2009-04-20

    Magnetic molecules ranging from simple organic radicals to single-molecule magnets (SMMs) are intensively investigated for their potential applications in molecule-based information storage and processing. The goal of this Article is to review recent achievements in the organization of magnetic molecules on surfaces and in their individual probing and manipulation. We stress that the inherent fragility and redox sensitivity of most SMM complexes, combined with the noninnocent role played by the substrate, ask for a careful evaluation of the structural and electronic properties of deposited molecules going beyond routine methods for surface analysis. Detailed magnetic information can be directly obtained using X-ray magnetic circular dichroism or newly emerging scanning probe techniques with magnetic detection capabilities.

  2. Ion-Molecule Reaction Dynamics.

    Science.gov (United States)

    Meyer, Jennifer; Wester, Roland

    2017-05-05

    We review the recent advances in the investigation of the dynamics of ion-molecule reactions. During the past decade, the combination of single-collision experiments in crossed ion and neutral beams with the velocity map ion imaging detection technique has enabled a wealth of studies on ion-molecule reactions. These methods, in combination with chemical dynamics simulations, have uncovered new and unexpected reaction mechanisms, such as the roundabout mechanism and the subtle influence of the leaving group in anion-molecule nucleophilic substitution reactions. For this important class of reactions, as well as for many fundamental cation-molecule reactions, the information obtained with crossed-beam imaging is discussed. The first steps toward understanding micro-solvation of ion-molecule reaction dynamics are presented. We conclude with the presentation of several interesting directions for future research.

  3. Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

    Directory of Open Access Journals (Sweden)

    Steven Karl Lundy

    2015-03-01

    Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

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

    Science.gov (United States)

    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. © 2016 Wiley Periodicals, Inc.

  5. Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer.

    Science.gov (United States)

    Hong, Chuyuan; Wei, Yisheng; Jiang, Jianxin; Zhao, Chuxiong; Liang, Guojian; Wang, Guoqiang; Yang, Hui

    2014-06-01

    To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer. In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model. The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer. © 2013 Wiley Publishing Asia Pty Ltd.

  6. Upregulation of adhesion molecules on leukemia targets improves the efficacy of cytotoxic T cells transduced with chimeric anti-CD19 receptor.

    Science.gov (United States)

    Laurin, David; Marin, Virna; Biagi, Ettore; Pizzitola, Irene; Agostoni, Valentina; Gallot, Géraldine; Vié, Henri; Jacob, Marie Christine; Chaperot, Laurence; Aspord, Caroline; Plumas, Joël

    2013-04-01

    T lymphocytes engineered to express chimeric antigen receptors (CARs) interact directly with cell surface molecules, bypassing MHC antigen presentation dependence. We generated human anti-CD19ζ CAR cytotoxic T lymphocytes and cytokine-induced killer cells and studied their sensitivity to the expression of adhesion molecules for the killing of primary B-lineage acute lymphoblastic leukemia (B-ALL) targets. Despite a very low basal expression of surface adhesion molecules, B-ALL blasts were lysed by the anti-CD19ζ-CAR transduced effectors as expected. We next investigated the regulatory role of adhesion molecules during CAR-mediated cytolysis. The blocking of these accessory molecules strongly limited the chimeric effector's cytotoxicity. Thereafter, B-ALL cells surface adhesion molecule level expression was induced by IFN-γ or by the combined use of CD40L and IL-4 and the cells were submitted to anti-CD19ζ-CAR transduced effectors lysis. Upregulation of adhesion molecules expression by blasts potentiated their killing. The improved cytotoxicity observed was dependent on target surface expression of adhesion molecules, particularly CD54. Taken together, these results indicate that adhesion molecules, and principally CD54, are involved in the efficiency of recognition by effector chimeric ζ. These observations have potential implications for the design of immunotherapy treatment approaches for hematological malignancies and tumors based on the adoption of CAR effector cells.

  7. Study of p53 protein expression levels from irradiated peripheral blood lymphocytes for biodosimetry

    International Nuclear Information System (INIS)

    Cavalcanti, M.B.; Fernandes, T.S.; Melo, J.A.; Neves, M.A.B.; Machado, C.G.F

    2005-01-01

    Biodosimetry can be defined as the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. Scoring of unstable chromosomal aberrations and micronuclei, from in vitro irradiated peripheral blood lymphocytes, is commonly used for biodosimetry based on cytogenetic analysis. However, this method of analysis is time-consuming, which may represent a pitfall when fast investigation of a possible exposure to ionizing radiation (IR) is needed. The interaction of IR with the living cell can cause injuries in the DNA molecules. However, normal cells possess mechanisms of repair that are capable to correct those damages. During the repair process of the DNA various proteins are expressed. Among these proteins, p53 plays an important role. This protein is a transcription factor that helps in the maintenance of the genomic integrity. p53 protein is found into the cytoplasm in reduced concentrations and has a short average life. However, expression of p53 protein can be induced by DNA harmful radioinduced, which increases the concentration and the average life of this protein, making possible its detection. Thus, the correlation between the increasing of p53 expression and the irradiation may constitute a fast and reliable method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the objective of this research was to evaluate the p53 protein expression levels from lymphocytes of the human peripheral blood after in vitro irradiation. For this, samples of peripheral blood from healthy individuals were irradiated with known doses. Lymphocytes were separated on ficoll gradient by centrifugation and re-suspended at 1x 10 6 /mL in RPMI medium enriched with fetal calf serum. Hence, lymphocytes were incubated in 5% CO 2 at 37 deg C prior to the methodology of flow cytometry, using intranuclear antigens for the quantification of p53. In this report, the methodology performed and the results obtained

  8. Study of p53 protein expression levels from irradiated peripheral blood lymphocytes for biodosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti, M.B.; Fernandes, T.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Amaral, A. [Universite Paris XII (UPXII) (France); Melo, J.A. [Centro de Radioterapia de Pernambuco (CERAPE), PE (Brazil); Neves, M.A.B.; Machado, C.G.F, E-mail: maribrayner@yahoo.com.br [Fundacao de Hematologia e Hemoterapia de Pernambuco, PE (Brazil)

    2005-07-01

    Biodosimetry can be defined as the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. Scoring of unstable chromosomal aberrations and micronuclei, from in vitro irradiated peripheral blood lymphocytes, is commonly used for biodosimetry based on cytogenetic analysis. However, this method of analysis is time-consuming, which may represent a pitfall when fast investigation of a possible exposure to ionizing radiation (IR) is needed. The interaction of IR with the living cell can cause injuries in the DNA molecules. However, normal cells possess mechanisms of repair that are capable to correct those damages. During the repair process of the DNA various proteins are expressed. Among these proteins, p53 plays an important role. This protein is a transcription factor that helps in the maintenance of the genomic integrity. p53 protein is found into the cytoplasm in reduced concentrations and has a short average life. However, expression of p53 protein can be induced by DNA harmful radioinduced, which increases the concentration and the average life of this protein, making possible its detection. Thus, the correlation between the increasing of p53 expression and the irradiation may constitute a fast and reliable method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the objective of this research was to evaluate the p53 protein expression levels from lymphocytes of the human peripheral blood after in vitro irradiation. For this, samples of peripheral blood from healthy individuals were irradiated with known doses. Lymphocytes were separated on ficoll gradient by centrifugation and re-suspended at 1x 10{sub 6}/mL in RPMI medium enriched with fetal calf serum. Hence, lymphocytes were incubated in 5% CO{sub 2} at 37 deg C prior to the methodology of flow cytometry, using intranuclear antigens for the quantification of p53. In this report, the methodology performed and the results

  9. Ibrutinib for treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Vela, Cory M; McBride, Ali; Jaglowski, Samantha M; Andritsos, Leslie A

    2016-03-15

    The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of ibrutinib are described. Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL). Ibrutinib blocks downstream signaling of the B-cell receptor, disrupting stromal microenvironment interactions and B-cell cytokine signaling. BTK inhibition has been shown to be effective in relapsed or refractory CLL. A recent Phase III study evaluated ibrutinib (420 mg daily) versus ofatumumab (consistent with labeling) in relapsed or refractory CLL with a primary endpoint of progression free survival (PFS, n = 391). After a median follow-up period of 9.4 months, a PFS was not attained in ibrutinib-treated individuals with and without deletion 17p. In contrast, ofatumumab-treated individuals experienced a PFS of 8.1 months and those with deletion 17p experienced a PFS of 5.8 months. Major hemorrhage was reported in 2 (1%) patients treated with ibrutinib, and a total of 8 (4%) patients discontinued treatment due to toxicity or adverse reactions. Partial response or partial response with lymphocytosis was achieved in 63% of ibrutinib-treated individuals as determined by independent assessments. Overall, ibrutinib reduced the rate of mortality by 57%. Ibrutinib is a first-in-class, orally active, irreversible BTK inhibitor with a novel mechanism of action. This unique mechanism of action and high overall response rates observed in clinical trials make ibrutinib an attractive second-line option in patients who have disease progression while receiving monoclonal antibody therapy or chemoimmunotherapy. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  10. Current Treatment of Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Jamroziak, Krzysztof; Puła, Bartosz; Walewski, Jan

    2017-01-01

    A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are already included into treatment algorithms defined by international practice guidelines, but more clinical investigations are needed to answer still remaining questions. Ibrutinib was proven as a primary choice for patients with the TP53 gene deletion/mutation, who otherwise have no active treatment available. Idelalisib with rituximab is also an active therapy, but due to increased risk of serious infections, its use in first-line treatment is limited to patients for whom ibrutinib is not an option. A new indication for ibrutinib was recently approved for older patients with comorbidities, as an alternative to the already existing indication for chlorambucil with obinutuzumab. The use of kinase inhibitors is already well established in recurrent/refractory disease. Immunochemotherapy with fludarabine, cyclophosphamide, rituximab (FCR) remains a major first-line option for many CLL patients without the TP53 gene deletion/mutation, and who have no significant comorbidities or history of infections, and is particularly effective in patients with favorable features including mutated IGHV status. There are a number of issues regarding novel therapies for CLL that need further investigation such as optimum duration of treatment with kinase inhibitors, appropriate sequencing of novel agents, mechanisms of resistance to inhibitors and response to class switching after treatment failure, along with the potential role of combinations of targeted agents.

  11. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  12. Single Molecule Electronics and Devices

    Science.gov (United States)

    Tsutsui, Makusu; Taniguchi, Masateru

    2012-01-01

    The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule. PMID:22969345

  13. Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer

    Directory of Open Access Journals (Sweden)

    Zhang L

    2017-03-01

    Full Text Available Lianru Zhang, Rutian Li, Hong Chen, Jia Wei, Hanqing Qian, Shu Su, Jie Shao, Lifeng Wang, Xiaoping Qian, Baorui Liu The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China Abstract: Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002. Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization. Keywords: cell membrane, drug delivery system, gastric cancer, low-dose irradiation, nanoparticles

  14. Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

    Science.gov (United States)

    Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

    2005-01-01

    Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

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

    International Nuclear Information System (INIS)

    Prusek, W.; Astaldi, G.

    1979-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-01-01

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

  17. The relationship between lymphocytes activated by pokeweed mitogen and by lipopolysaccharides and their radiosensitivity

    International Nuclear Information System (INIS)

    Su Liaoyuan; Liu Fenju; Liu Keliang; Xu Changshao; Xu Yingdong; Geng Yongzhi

    1992-07-01

    Human whole blood was incubated in vitro. Lymphocytes were activated by poke-weed mitogen (PWM) and by Lipopolysaccharides (LPS). The relationship between the two kinds of lymphocytes was investigated using radioactive compound incorporation. The study showed that PWM-activated lymphocytes were able to promote the stimulating effect of LPS on B lymphocytes. The stimulating effect of PWM-activated lymphocytes was obviously decreased after they were irradiated with 10 Gy gamma rays. When PWM-activated lymphocytes and LPS-activated lymphocytes were incubated together after one of the cell populations had been exposed 10 Gy 60 Co gamma rays, the incorporation of [ 3 H] TdR was much decreased and the synergistic function disappeared, especially when the PWM-activated lymphocytes were irradiated. In cells from patients treated with 60 Co gamma rays for carcinoma of nasopharynx, the incorporation in LPS-activated lymphocytes approached normal levels while that in PWM-activated lymphocytes was reduced significantly and the stimulating effect of PWM-activated lymphocytes on LPS-activated lymphocytes was also markedly reduced. These demonstrate that PWM-activated lymphocytes have a similar function to T-helper cells and seem to be more radiosensitive than LPS-activated lymphocytes

  18. Spin tunneling in magnetic molecules

    Science.gov (United States)

    Kececioglu, Ersin

    In this thesis, we will focus on spin tunneling in a family of systems called magnetic molecules such as Fe8 and Mn12. This is comparatively new, in relation to other tunneling problems. Many issues are not completely solved and/or understood yet. The magnetic molecule Fe 8 has been observed to have a rich pattern of degeneracies in its magnetic spectrum. We focus on these degeneracies from several points of view. We start with the simplest anisotropy Hamiltonian to describe the Fe 8 molecule and extend our discussion to include higher order anisotropy terms. We give analytical expressions as much as we can, for the degeneracies in the semi-classical limit in both cases. We reintroduce jump instantons to the instanton formalism. Finally, we discuss the effect of the environment on the molecule. Our results, for all different models and techniques, agree well with both experimental and numerical results.

  19. Experimental decoherence in molecule interferometry

    International Nuclear Information System (INIS)

    Hackermueller, L.; Hornberger, K.; Stibor, A.; Zeilinger, A.; Arndt, M.; Kiesewetter, G.

    2005-01-01

    Full text: We present three mechanisms of decoherence that occur quite naturally in matter wave interferometer with large molecules. One way molecules can lose coherence is through collision with background gas particles. We observe a loss of contrast with increasing background pressure for various types of gases. We can understand this phenomenon quantitatively with a new model for collisional decoherence which corrects older models by a factor of 2 π;. The second experiment studies the thermal emission of photons related to the high internal energy of the interfering molecules. When sufficiently many or sufficiently short photons are emitted inside the interferometer, the fringe contrast is lost. We can continuously vary the temperature of the molecules and compare the loss of contrast with a model based on decoherence theory. Again we find good quantitative agreement. A third mechanism that influences our interference pattern is dephasing due to vibrations of the interference gratings. By adding additional vibrations we study this effect in more detail. (author)

  20. [Occurrence of associated tumours in chronic lymphocytic leukemia].

    Science.gov (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt

    2016-10-01

    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  1. Photoionization of atoms and molecules

    International Nuclear Information System (INIS)

    Samson, J.A.R.

    1976-01-01

    A literature review on the present state of knowledge in photoionization is presented. Various experimental techniques that have been developed to study photoionization, such as fluorescence and photoelectron spectroscopy, mass spectroscopy, are examined. Various atoms and molecules were chosen to illustrate these techniques, specifically helium and xenon atoms and hydrogen molecules. Specialized photoionization such as in positive and negative ions, excited states, and free radicals is also treated. Absorption cross sections and ionization potentials are also discussed

  2. Low pressure tritiation of molecules

    International Nuclear Information System (INIS)

    Moran, T.F.; Powers, J.C.; Lively, M.O.

    1980-01-01

    A method is described of tritiating sensitive biological molecules by depositing molecules of the substance to be tritiated on a supporting substrate in an evacuated vacuum chamber near, but not in the path of, an electron beam which traverses the chamber, admitting tritium gas into the chamber, and subjecting the tritium to the electron beam. Vibrationally excited tritium gas species are generated which collide and react with the substance thus incorporating tritium atoms into the substance. (U.K.)

  3. Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

    Science.gov (United States)

    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.

  4. Lymphocytic Panhypophysitis: Its Clinical Features in Japanese Cases

    Directory of Open Access Journals (Sweden)

    Yoshiharu Wada

    2011-01-01

    Full Text Available Lymphocytic hypophysitis is divided into three forms according to the involved tissues, lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis, and lymphocytic panhypophysitis (LPH. The term LPH was first proposed by us in 1995, although its entity and pathogenesis still remain controversial. Here we report five cases of LPH, who visited our clinics during 1994 to 2009. All cases were female of 20 to 77 years of age, and one case was associated with pregnancy. They presented with polyuria (n = 4, headache (n = 3, general malaise, polydipsia (n = 2, blunted vision, diplopia, amenorrhea or appetite loss (n = 1. Magnetic resonance imaging showed the pituitary swelling, the thickened stalk, the loss of the T1 hyperintense neurohypophysis (n = 4, or the atrophic pituitary (n = 1. Endocrinological examinations revealed deficiencies of TSH, ADH in all cases, GH, ACTH in three cases, LH, PRL in two cases, and FSH in one case, respectively. The severity of ADH deficiency varied among the cases. Anti-pituitary antibody was not detected in the cases examined. The biopsy of the pituitary lesions was performed except for one case, all of which revealed the diffuse lymphocytic infiltration. These results suggest that LPH is characterized by the female predominance, the atypical patterns of anterior pituitary hormone deficiencies and the variable degrees of diabetes insipidus in Japanese.

  5. Fate of lymphocytes after withdrawal of tofacitinib treatment.

    Science.gov (United States)

    Piscianz, Elisa; Valencic, Erica; Cuzzoni, Eva; De Iudicibus, Sara; De Lorenzo, Elisa; Decorti, Giuliana; Tommasini, Alberto

    2014-01-01

    Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.

  6. Fate of lymphocytes after withdrawal of tofacitinib treatment.

    Directory of Open Access Journals (Sweden)

    Elisa Piscianz

    Full Text Available Tofacitinib (Tofa is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.

  7. Lymphocyte subsets and response to PHA among atomic bomb survivors

    International Nuclear Information System (INIS)

    Nakao, Susumu; Noguchi, Kyouichi; Eida, Kazuyuki; Tashiro, Kazunori; Hayashida, Ken

    1986-01-01

    In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

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

    Directory of Open Access Journals (Sweden)

    Khadijeh Khosravi

    2016-05-01

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

  9. Thermal ion-molecule reactions in oxygen-containing molecules

    International Nuclear Information System (INIS)

    Kumakura, Minoru

    1981-02-01

    The energetics of ions and the thermal ion-molecule reactions in oxygen-containing molecules have been studied with a modified time-of-flight mass spectrometer. It was found that the translational energy of ion can be easily obtained from analysis of the decay curve using the time-of-flight mass spectrometer. The condensation-elimination reactions proceeded via cross- and homo-elimination mechanism in which the nature of intermediate-complex could be correlated with the nature of reactant ion. It was elucidated that behavior of poly-atomic oxygen-containing ions on the condensation-elimination reactions is considerably influenced by their oxonium ion structures having functional groups. In addition, the rate constants of the condensation-elimination reactions have affected with the energy state of reactant ion and the dipole moment and/or the polarizability of neutral molecule. It was clarified that the rate constants of the ion-molecule clustering reactions in poly-atomic oxygen-containing molecules such as cyclic ether of six member rings are very large and the cluster ions are stable owing to the large number of vibrational degree of freedom in the cluster ions. (author)

  10. Kinetics of human lymphocyte division and chromosomal radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, N O; Bianchi, M S; Larramendy, M [Instituto Multidisciplinario de Biologia Celular, La Plata (Argentinia)

    1979-12-01

    Human blood from normal donors was irradiated with 200 R during the G/sub 0/ phase, and the X-ray sensitivity of early and late dividing lymphocytes in culture was expressed as percentage of induced dicentrics. Cells in first or subsequent divisions were individualized by BrdU-Giemsa techniques. Lymphocytes in the first division at 40, 44 and 72 h after the start of culture had a lower sensitivity to radiation than lymphocytes making their first division at 48, 52 and 56 h. It was observed that: (a) the combination of radiation followed by BrdU did not increase the clastoyenic action of X-rays, (b)X-rays in the dose and duration used in our cultures did not increase the frequency of SCEs, and (c) minor changes in culture conditions probably influenced the frequency of SCEs.

  11. Whole blood microculture assay of human lymphocyte function.

    Science.gov (United States)

    Pauly, J L; Han, T

    1976-11-01

    A whole blood microculture assay is described for measuring lymphocyte reactivity to mitogenic and antigenic stimulants. This assay employs heparinized whole blood, serum-free culture medium, microtiter plates, and a Multiple Automated Sample Harvester (MASH). When this assay is compared to other leukocyte assays, its major advantages include (1) the utilization of fewer lymphocytes per microculture, thuus reducing the amount of blood required per test while increasing the number of test agents and replicate cultures which can be employed in any given experiment; (2) the conservation of mitogens, antigens, drugs, enzymes, hormones, lymphokines, and other test agents, some of which are either expensive of difficult to prepare in large quantities; (3) the elimination of lymphocyte isolation and purification procedures which may disrupt the relative proportion of T cells, B cells and antigen-processing cells; and (4) the application of an automated harvester which simplifies and expedites procedures required for processing cells for liquid scintillation counting.

  12. Radioprotective effect of antioxidants on human blood lymphocytes

    International Nuclear Information System (INIS)

    Wang Mingsuo; Gu Xuandi; Zhu Genbo; Feng Jixing; Su Liaoyuan

    1991-09-01

    By using an improved fluorometric method with 2-thiobarbituric acid (TBA) as fluorometric agent, the antiradiation effects of four kinds of antioxidants on 60 Co γ-ray irradiation inducing final products of lipid peroxides (LPO), i.e. malodialdehyde (MDA) content changes in human blood lymphocytes, were investigated with LPO value as an indicator. The results of the experiment were as following: (1)The radioprotective effect of exogenous antioxidants added to human blood lymphocytes on radiation-induced LPO damage of cellular membrane were remarkable; (2)The radioprotective beneficial sequences of four kinds of antioxidants were arranged like this: SOD > VE >VC, Se 4+ ; (3)Radioprotective effects of antioxidants on radiation-induced damage varied especially with the property of antioxidants, drug concentration, and pretreatment and monitoring time, etc., as well as irradiated dosage and various kinds of incubated cells. In addition, the mechanism of these antioxidants as radioprotectants on human blood lymphocytes is discussed in connection with LPO damage and radioprotection

  13. Genetically enhanced T lymphocytes and the intensive care unit

    Science.gov (United States)

    Tat, Tiberiu; Li, Huming; Constantinescu, Catalin-Sorin; Onaciu, Anca; Chira, Sergiu; Osan, Ciprian; Pasca, Sergiu; Petrushev, Bobe; Moisoiu, Vlad; Micu, Wilhelm-Thomas; Berce, Cristian; Tranca, Sebastian; Dima, Delia; Berindan-Neagoe, Ioana; Shen, Jianliang; Tomuleasa, Ciprian; Qian, Liren

    2018-01-01

    Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment. PMID:29662667

  14. MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

    Directory of Open Access Journals (Sweden)

    S. V. Khaidukov

    2009-01-01

    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  15. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang D

    2013-03-01

    Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

  16. Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

    Science.gov (United States)

    Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves

    2015-02-01

    To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

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

    KAUST Repository

    Hill-Cawthorne, Grant A.; Button, Tom; Tuohy, Orla C.; Jones, Joanne L.; May, Karen; Somerfield, Jennifer; Green, Alison J E; Giovannoni, Gavin; Compston, Alastair D.; Fahey, Michael T.; Coles, Alasdair J.

    2011-01-01

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

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

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

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

  19. The Molecule Cloud - compact visualization of large collections of molecules

    Directory of Open Access Journals (Sweden)

    Ertl Peter

    2012-07-01

    Full Text Available Abstract Background Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. Summary A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach “Molecule Cloud”. The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Conclusions Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large

  20. CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

    2017-08-01

    CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

  1. Molecule-by-Molecule Writing Using a Focused Electron Beam

    DEFF Research Database (Denmark)

    Van Dorp, Willem F.; Zhang, Xiaoyan; Feringa, Ben L.

    2012-01-01

    atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor...... on graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...... investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average...

  3. The chromosomal radiosensitivity of lymphocytes from the chimpanzee (Pan troglodytes)

    International Nuclear Information System (INIS)

    Leonard, A.; Decat, G.; Leonard, E.D.; Mortelmans, J.

    1977-01-01

    The yield of chromosomal aberrations induced by exposure to X-irradiation in vitro was studied in the lymphocytes of the chimpanzee (Pan troglodytes), a hominoid ape phylogenically and chromosomally closely related to man. In agreement with the similarity of the chromosome characteristics, no significant difference was observed between man and chimpanzee with respect to the incidence of dicentrics and fragments. It is obvious that the nuclear area, which apparently constitutes the most evident difference between the nuclei of man and chimpanzee lymphocytes, did not play an important role in the yields of aberrations

  4. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    Does-van den Berg, A. van der.

    1980-01-01

    Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

  5. DNA repair deficiency in lymphocytes from patients with actinic keratosis

    International Nuclear Information System (INIS)

    Abo-Darub, J.M.; Mackie, R.; Pitts, J.D.

    1978-01-01

    DNA repair activity was measured in peripheral blood lymphocytes from 18 patients with Actinic Keratosis and 18 age-matched control subjects, by comparing the incorporation of 3 H-thymidine into cells after irradiation with ultraviolet light with that into unirradiated cells. The incorporation was followed autoradiographically or by measuring acid insoluble radioactivity in cells labelled in the presence of hydroxyurea. The repair activity in lymphocytes from Actinic keratosis patients was only 47.1% (+-6.5%) of that in cells from the control subjects

  6. What Are the Molecules Involved in Regulatory T-Cells Induction by Dendritic Cells in Cancer?

    Directory of Open Access Journals (Sweden)

    Rodrigo Nalio Ramos

    2013-01-01

    Full Text Available Dendritic cells (DCs are essential for the maintenance of homeostasis in the organism, and they do that by modulating lymphocyte priming, expansion, and response patterns according to signals they receive from the environment. The induction of suppressive lymphocytes by DCs is essential to hinder the development of autoimmune diseases but can be reverted against homeostasis when in the context of neoplasia. In this setting, the induction of suppressive or regulatory T cells contributes to the establishment of a state of tolerance towards the tumor, allowing it to grow unchecked by an otherwise functional immune system. Besides affecting its local environment, tumor also has been described as potent sources of anti-inflammatory/suppressive factors, which may act systemically, generating defects in the differentiation and maturation of immune cells, far beyond the immediate vicinity of the tumor mass. Cytokines, as IL-10 and TGF-beta, as well as cell surface molecules like PD-L1 and ICOS seem to be significantly involved in the redirection of DCs towards tolerance induction, and recent data suggest that tumor cells may, indeed, modulate distinct DCs subpopulations through the involvement of these molecules. It is to be expected that the identification of such molecules should provide molecular targets for more effective immunotherapeutic approaches to cancer.

  7. Physics of Complex Polymeric Molecules

    Science.gov (United States)

    Kelly, Joshua Walter

    The statistical physics of complex polymers with branches and circuits is the topic of this dissertation. An important motivation are large, single-stranded (ss) RNA molecules. Such molecules form complex ``secondary" and ``tertiary" structures that can be represented as branched polymers with circuits. Such structures are in part directly determined by the nucleotide sequence and in part subject to thermal fluctuations. The polymer physics literature on molecules in this class has mostly focused on randomly branched polymers without circuits while there has been minimal research on polymers with specific structures and on polymers that contain circuits. The dissertation is composed of three parts: Part I studies branched polymers with thermally fluctuating structure confined to a potential well as a simple model for the encapsidation of viral RNA. Excluded volume interactions were ignored. In Part II, I apply Flory theory to the study of the encapsidation of viral ss RNA molecules with specific branched structures, but without circuits, in the presence of excluded volume interaction. In Part III, I expand on Part II and consider complex polymers with specific structure including both branching and circuits. I introduce a method based on the mathematics of Laplacian matrices that allows me to calculate density profiles for such molecules, which was not possible within Flory theory.

  8. Quantum transport through organic molecules

    International Nuclear Information System (INIS)

    Maiti, Santanu K.

    2007-01-01

    We investigate the electronic transport for the model of benzene-1, 4-dithiolate (BDT) molecule and some other geometric models of benzene molecule attached with two semi-infinite metallic electrodes by the use of Green's function technique. An analytic approach for the electronic transport through the molecular bridges is presented, based on the tight-binding model. Transport of electrons in such molecular bridges is strongly affected by the geometry of the molecules and their coupling strength with the electrodes. Conductance (g) shows resonance peaks associated with the molecular energy eigenstates. In the weak molecule-to-electrodes coupling limit current (I) passing through the molecules shows staircase-like behavior with sharp steps, while, it varies quite continuously in the limit of strong molecular coupling with the applied bias voltage (V). In presence of the transverse magnetic field conductance gives oscillatory behavior with flux φ, threaded by the molecular ring, showing φ 0 ( = ch/e) flux-quantum periodicity. Though conductance changes with the application of transverse magnetic field, but the current-voltage characteristics remain same in presence of this magnetic field for these molecular bridge systems

  9. Dissociation and decay of ultracold sodium molecules

    International Nuclear Information System (INIS)

    Mukaiyama, T.; Abo-Shaeer, J.R.; Xu, K.; Chin, J.K.; Ketterle, W.

    2004-01-01

    The dissociation of ultracold molecules was studied by ramping an external magnetic field through a Feshbach resonance. The observed dissociation energies directly yielded the strength of the atom-molecule coupling. They showed nonlinear dependence on the ramp speed. This was explained by a Wigner threshold law which predicts that the decay rate of the molecules above threshold increases with the density of states. In addition, inelastic molecule-molecule and molecule-atom collisions were characterized

  10. HLA-G molecule as inductor of immunotolerance

    International Nuclear Information System (INIS)

    Alfonso Valdes, Maria E

    2009-01-01

    HLA-G are molecules are (non-classic) class I antigens from main histocompatibility system. There are sis isoforms of HLA-G antigen codifying four proteins united to a membrane (HLA-G1, HLA-G2, HLA-G3, HLA-G4), and three soluble isoforms (HLA-G5, HLA-G6, HLA-G7). The first ones are expressed in cells of placental extravillous cytotrophoblast (Langhans' layer), amnios epithelial cells, fetal endothelial cells, mesenchymal macrophages of chorionic villi, and in epithelial cells of thymus medulla; the second ones in amniotic fluid, in maternal peripheral blood and that of the umbilical cord. There was a HLA-G expression in some types of tumors, stroma cells under inflammation conditions, virus-infected cells and in serum of transplant patients. There are strong evidences of HLA-G molecules role in tolerance induction to these physiological and pathological situations through suppression of lithic activity of NK cells and of cytotoxic T lymphocytes. This knowledge may be very useful in future therapeutical management of these entities as well as to favor the success of tissue and organ transplant

  11. Small molecule fluoride toxicity agonists.

    Science.gov (United States)

    Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

    2015-04-23

    Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Double photoionisation spectra of molecules

    CERN Document Server

    Eland, John

    2017-01-01

    This book contains spectra of the doubly charged positive ions (dications) of some 75 molecules, including the major constituents of terrestrial and planetary atmospheres and prototypes of major chemical groups. It is intended to be a new resource for research in all areas of molecular spectroscopy involving high energy environments, both terrestrial and extra-terrestrial. All the spectra have been produced by photoionisation using laboratory lamps or synchrotron radiation and have been measured using the magnetic bottle time-of-flight technique by coincidence detection of correlated electron pairs. Full references to published work on the same species are given, though for several molecules these are the first published spectra. Double ionisation energies are listed and discussed in relation to the molecular electronic structure of the molecules. A full introduction to the field of molecular double ionisation is included and the mechanisms by which double photoionisation can occur are examined in detail. A p...

  13. Altered expression of adhesion molecules on peripheral blood leukocytes in feline infectious peritonitis.

    Science.gov (United States)

    Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Desmarets, Lowiese M B; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-10-25

    Feline infectious peritonitis (FIP) is a fatal, coronavirus-induced systemic disease in domestic and wild felids. The pathology associated with FIP (multifocal granulomatous vasculitis) is considered to be elicited by exaggerated activation and subsequent extravasation of leukocytes. As changes in the expression of adhesion molecules on circulating leukocytes precede their margination and emigration, we reasoned that the expression of leukocyte adhesion molecules may be altered in FIP. In present study, the expression of principal adhesion molecules involved in leukocyte transmigration (CD15s, CD11a, CD11b, CD18, CD49d, and CD54) on peripheral blood leukocytes from cats with naturally occurring FIP (n=15) and controls (n=12) was quantified by flow cytometry using a formaldehyde-based rapid leukocyte preparation technique. T- and B-lymphocytes from FIP patients exhibit higher expression of both subunits (CD11a and CD18) composing the β2 integrin lymphocyte function-associated antigen (LFA)-1. In addition, the expression of the α4 subunit (CD49d) of the β1 integrin very late antigen (VLA)-4 was elevated on B-lymphocytes from FIP patients. The expression of CD11b and CD18, that combine to form the β2 integrin macrophage-1 antigen (Mac-1), was elevated on monocytes, whereas the density of CD49d was reduced on this population in FIP. Granulocytes of FIP cats displayed an increased expression of the α chain of Mac-1 (CD11b). These observations suggest that leukocytes from FIP patients show signs of systemic activation causing them to extravasate into surrounding tissues and ultimately contribute to pyogranuloma formation seen in FIP. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

    NARCIS (Netherlands)

    van Attekum, Martijn H. A.; Eldering, Eric; Kater, Arnon P.

    2017-01-01

    The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander

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

    Science.gov (United States)

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

    2001-12-01

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

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

    Science.gov (United States)

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

  17. Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes

    NARCIS (Netherlands)

    Nijhara, Ruchika; van Hennik, Paula B.; Gignac, Michelle L.; Kruhlak, Michael J.; Hordijk, Peter L.; Delon, Jerome; Shaw, Stephen

    2004-01-01

    Lymphocytes circulate in the blood and upon chemokine activation rapidly bind, where needed, to microvasculature to mediate immune surveillance. Resorption of microvilli is an early morphological alteration induced by chemokines that facilitates lymphocyte emigration. However, the antecedent

  18. Technetium-aspirin molecule complexes

    International Nuclear Information System (INIS)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M.

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author)

  19. Teaching lasers to control molecules

    International Nuclear Information System (INIS)

    Judson, R.S.; Rabitz, H.

    1992-01-01

    We simulate a method to teach a laser pulse sequences to excite specified molecular states. We use a learning procedure to direct the production of pulses based on ''fitness'' information provided by a laboratory measurement device. Over a series of pulses the algorithm learns an optimal sequence. The experimental apparatus, which consists of a laser, a sample of molecules and a measurement device, acts as an analog computer that solves Schroedinger's equation n/Iexactly, in real time. We simulate an apparatus that learns to excite specified rotational states in a diatomic molecule

  20. Exotic helium molecules; Molecules exotiques d'helium

    Energy Technology Data Exchange (ETDEWEB)

    Portier, M

    2007-12-15

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}P{sub 0}) molecule, or a {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 {+-} 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime {tau} = (1.4 {+-} 0.3) {mu}s is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  1. Exotic helium molecules; Molecules exotiques d'helium

    Energy Technology Data Exchange (ETDEWEB)

    Portier, M

    2007-12-15

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}P{sub 0}) molecule, or a {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 {+-} 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime {tau} = (1.4 {+-} 0.3) {mu}s is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  2. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

    OpenAIRE

    van Attekum, Martijn HA; Eldering, Eric; Kater, Arnon P

    2017-01-01

    The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenv...

  3. CHARACTERIZATION OF TWO MONOCLONAL ANTIBODIES WHICH RECOGNIZE DIFFERENT SUBPOPULATIONS OF CHICKEN T LYMPHOCYTES

    OpenAIRE

    KONDO, Takashi; HATTORI, Masakazu; KODAMA, Hiroshi; ONUMA, Misao; MIKAMI, Takeshi

    1990-01-01

    Distribution among peripheral T lymphocyte subpopulations and biochemical properties of the chicken lymphocyte surface antigens defined by monoclonal antibodies (mAbs) Lc-4 and Lc-6 were examined. Two-color immunofluorescence analysis revealed that Lc-4 and Lc-6 antigens were expressed on mutually exclusive subpopulations of peripheral T lymphocytes but not on B lymphocytes. Lc-4 mAb precipitated a polypeptide with apparent molecular mass of 35 and 65 kilodalton under reducing and non-reducin...

  4. T-cell-mediated immunity to lymphocytic choriomeningitis virus in beta2-integrin (CD18)- and ICAM-1 (CD54)-deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1996-01-01

    The T-cell response to lymphocytic choriomeningitis virus was studied in mice with deficient expression of beta2-integrins or ICAM-1. In such mice, the generation of virus-specific cytotoxic T lymphocytes was only slightly impaired and bystander activation was as extensive as that observed in wild-type...... mice. T-cell-mediated inflammation, assessed as primary footpad swelling and susceptibility to intracerebral infection, was slightly compromised only in beta2-integrin-deficient mice. However, adoptive immunization of mutant mice soon after local infection did reveal a reduced capacity to support...... the inflammatory reaction, indicating that under conditions of more limited immune activation both molecules do play a role in formation of the inflammatory exudate. Finally, virus control was found to be somewhat impaired in both mutant strains. In conclusion, our results indicate that although LFA-1-ICAM-1...

  5. Activation of cytotoxic lymphocytes in patients with scrub typhus

    NARCIS (Netherlands)

    de Fost, Maaike; Chierakul, Wirongrong; Pimda, Kriangsak; Dondorp, Arjen M.; White, Nicholas J.; van der Poll, Tom

    2005-01-01

    Thai patients with scrub typhus caused by the intracellular pathogen Orientia tsutsugamushi displayed elevated plasma concentrations of granzymes A and B, interferon-gamma (IFN)-gamma-inducible protein 10, and monokine induced by IFN-gamma. These data suggest that activation of cytotoxic lymphocytes

  6. Range-reference determination of lymphocyte subsets in Moroccan

    African Journals Online (AJOL)

    Administrator

    Centre de Transfusion Sanguine, Hôpital Militaire d'Instruction Med V Rabat, Morocco. 3. Service ... The percentage of CD3-CD56+ subsets was affected by smoking (p < 0.01). Our analysis .... lymphocyte subpopulations in non-smokers and.

  7. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors

    DEFF Research Database (Denmark)

    Xochelli, Aliki; Baliakas, Panagiotis; Kavakiotis, Ioannis

    2017-01-01

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether...

  8. Lymphocyte as a biological dosimeter : a different approach

    International Nuclear Information System (INIS)

    Madhvanath, U.

    1974-01-01

    Chromosome aberration frequency as a measure of radiation exposure in human blood lymphocytes following a short term culture is well known and the technique is in use at several laboratories in the world to determine accidental exposures. Results of an entirely different approach to arrive at the exposure is presented. Time course of interphase death of human peripheral blood lymphocytes was followed for 6 days after exposure to cobalt-60 gamma radiation. Trypan blue dye exclusion method was used for scoring viable cells. Survival curves at 5 days post irradiation were exponential and had two components: an initial sensitive component representing a major sub-population of lymphocytes with a mean lethal dose (DO) of 75 rads and the other an apparently more resistant population with a Do of about 300 rads. The initial part of the survival curve which spans to about 100 rads reaching a survival level of 15 percent, can be used to read off the extent of exposure in accident cases. Although 60 percent of the initial lymphocytes survive in the unexposed control cultures, the method is sensitive to exposures of the order of 20 rads and reproducible results have been obtained. The response is independent of dose-rate from 65 rads/min to 65 rads/hour. Other aspects of the dosimetry system such as the neutron response, in vitro and in vivo correlation are discussed. (author)

  9. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    OpenAIRE

    Benjamin Arthurs, MD; Kathy Wunderle, MD; Maylee Hsu, MD; Suil Kim, MD, PhD

    2017-01-01

    We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  10. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Arthurs, MD

    2017-01-01

    Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  11. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia.

    Science.gov (United States)

    Arthurs, Benjamin; Wunderle, Kathy; Hsu, Maylee; Kim, Suil

    2017-01-01

    We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus . Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  12. Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

    African Journals Online (AJOL)

    EL-HAKIM

    biochemical features.2 It is a coordinated series of events for the ... sex matched subjects with no clinical or laboratory signs or family history of ... Keywords: lymphocyte apoptosis; CD95 system; type 1 DM; prediabetes. Eman M. ..... percentage among complicated and non-complicated cases of type-1 diabetes mellitus.

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

    NARCIS (Netherlands)

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

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

  14. Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

    Centers for Disease Control (CDC) Podcasts

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

  15. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell ... alleles were more resistant to clinical mastitis. ... DRB3.2 allele pattern in two Iranian Holstein cow .... observed and the number of immune parameters with.

  16. Production of C-reactive protein by human lymphocytes

    International Nuclear Information System (INIS)

    Kuta, A.E.; Baum, L.L.

    1986-01-01

    C-reactive protein (CRP) is a major acute phase serum protein in humans; it is detectable at very high concentrations during infection and tissue trauma. This protein is a pentame composed of five identical, 21,500 MW subunits. CRP is detectable on the surface of approximately 4% of normal peripheral blood lymphocytes (PBL). CRP binds its physiological ligands in a Ca ++ dependent manner; removal of Ca ++ does not alter the expression of CRP on the lymphocyte surface. Recently, investigators in this laboratory reported substantial inhibition of natural killer cell (NK) activity with anti-CRP antibodies. The following studies were undertaken to determine the origin of surface-CRP (S-CRP) found on normal PBL. Cells were incubated in methionine-free DMEM supplemented with 35 S-methionine. Cells were lysed and subjected to immunoprecipitation with anti-CRP and Staphylococcus aureus; immunoprecipitates were analyzed by SDS-PAGE and autoradiography. Data presented here suggested that lymphocytes, in particular, LGL produce small amounts of CRP and express it on their surface. Lymphocytes do not appear to secrete CRP since no CRP could be detected in culture supernatants. In addition, preliminary evidence indicates that peripheral blood monocytes produce no detectable CRP. Present studies utilizing Northern blot analysis are underway in order to detect CRP-mRNA

  17. Platelet indices and neutrophil to lymphocyte ratio in adults with ...

    African Journals Online (AJOL)

    Background: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Methods: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with ...

  18. T-lymphocyte subsets, thymic size and breastfeeding in infancy

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M

    2004-01-01

    We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4...

  19. Case Report: A child with acute lymphocytic leukaemia

    African Journals Online (AJOL)

    The patient was a child aged 5 years who had been diagnosed to have acute lymphocytic leukemia (ALL). Chemotherapy was given with wysolone, vincristine, daunomycin, l-asparaginase, and intrathecal methotrexate. In addition he was given fluconazole and co-trimoxazole to cover infections during the induction period ...

  20. Lymphocytic cholangitis in cats: a microbiological, histological and clinical approach

    NARCIS (Netherlands)

    Otte, C.M.A.

    2017-01-01

    In this thesis, a general overview is given of the healthy feline liver and feline diseases of the gall bladder and biliary tree. Lymphocytic cholangitis (LC) is one of the most common inflammatory hepatic diseases in cats. It is a chronic disease that affects the biliary tree and progresses slowly

  1. Monitoring of cardiac antirejection therapy with 111In lymphocytes

    International Nuclear Information System (INIS)

    Lerch, R.A.; Bergmann, S.R.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-01-01

    To determine whether lymphocytes labeled with 111 In permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with 111 In were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of 111 In lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with 111 In-labeled lymphocytes will permit noninvasive assessment of antirejection therapy

  2. Genotoxic damage in cultured human peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Falaq Naz

    2012-06-29

    Jun 29, 2012 ... Genotoxic damage in cultured human peripheral blood lymphocytes of oral ... catechol estrogens and quinines, via redox reactions causes oxidative damage to .... volume was prepared for each donor. About, 0.8 ml of cell sus .... duce the adverse effects of OCs, such as the reduction in the estrogen content.

  3. Effects of noise exposure on catalase activity of growing lymphocytes

    Directory of Open Access Journals (Sweden)

    Syed Kashif Nawaz

    2012-11-01

    Full Text Available Oxidative stress due to noise was estimated at cell level using model of growing lymphocytes. Lymphocytes were isolated and cultured using conventional methodology. Cell culture of each group was exposed to sound of frequency 1 KHz during incubation. Three groups were defined on the basis of exposure of sound with specific range of intensity and duration of exposure. Group A and Group B were exposed to sound with intensity 110 dBA for four hours per day and for eight hours per day respectively. Control group was exposed to sound less than 85 dBA. Viable cell count was performed using trypan blue. Catalase activity of each group was estimated using ELISA kit.Viable cell count of Group A and Group B was almost same but significantly less than that of control group. Catalase activity of lymphocytes in Group B was significantly low as compared to Group A and controls (p=0.003,p< 0.05. There was no significant difference between catalase activity of Group A and control group.Exposure of sound with frequency 1 KHz and intensity 110 dBA for 4 hours and eight hours per day may induce oxidative stress in growing lymphocytes causing the difference in viable cell count. However the catalase activity depends on duration of exposure. In case of noise exposure of 8 hours per day, it declines significantly as compared to noise exposure of 4 hours per day.

  4. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-06-01

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

  5. Spleen lymphocyte function modulated by a cocoa-enriched diet.

    Science.gov (United States)

    Ramiro-Puig, E; Pérez-Cano, F J; Ramírez-Santana, C; Castellote, C; Izquierdo-Pulido, M; Permanyer, J; Franch, A; Castell, M

    2007-09-01

    Previous studies have shown the down-regulating in vitro effect of cocoa flavonoids on lymphocyte and macrophage activation. In the present paper, we report the capacity of a long-term rich cocoa diet to modulate macrophage cytokine secretion and lymphocyte function in young rats. Weaned rats received natural cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for 3 weeks. Spleen immune function was then evaluated through the analysis of lymphocyte composition, their proliferative response and their ability to secrete cytokines and Ig. In addition, the status of activated peritoneal macrophages was established through tumour necrosis factor (TNF)-alpha secretion. The richest cocoa diet (10%) caused a reduction of TNF-alpha secretion by peritoneal macrophages showing anti-inflammatory activity. Similarly, although a 10% cocoa diet increased lymphocyte proliferation rate, it down-regulated T helper 2 (Th2)-related cytokines and decreased Ig secretion. These changes were accompanied by an increase in spleen B cell proportion and a decrease in Th cell percentage. In summary, these results demonstrate the functional activity of a cocoa-high dosage in down-regulating the immune response that might be beneficial in hypersensitivity and autoimmunity.

  6. Protective effect of citrullus vulgaris on irradiated lymphocyte membrane ultrastructure

    International Nuclear Information System (INIS)

    Khairul Osman; Norashikin, M.S.; Hing Hiang Lian; Siti Fatimah Ibrahim; Seetha Khartini Abdul Wahab; Jamaludin Mohamed; Proom Promwichit

    2004-01-01

    Radiotherapy causes various complications including low immunity. Past research that the low immunity is due to the low amount of lymphocytes and consumption vulgaris will alleviate this problem. Based on this a study was conducted to identify vulgaris was able to produce radioprotection on the lymphocyte membrane. A total of 30 adult male Sprague-Dawley rats were used and divided into three equals groups of positive control and treatment. For seven days, positive control and negative control were force fed with normal saline of 40 ml/kg animal weight while the treatment group received 40g/kg animal weight fresh juice of citrullus vulgaris daily. After a week positive control an group were irradiated with 0.9 Gy gamma ray. Viable lymphocyte were determined using propidium iodine and acridine orange stain. Results clearly shows that positive con and treatment group were significantly different at 34 ± 3% , 80 ± 2% an 71 ± 2% respectively. SEM results shows that pores were present on the membrane of the pos while the negative control had none. Similar results were also found on the treatment group. Based on the result it had shown that citrullus vulgaris had radioprotection properties and lymphocytes were destroyed by the formation of pores on their membrane. It is very likely that the radioprotection properties could be due to the presence of antioxidants particularly vitamin A, C and lycopene. In conclusion, citrullus vulgaris could be used as a safe radioprotection agent. (Author)

  7. Changes in total and differential white cell counts, total lymphocyte ...

    African Journals Online (AJOL)

    Background: Published reports on the possible changes in the various immune cell populations, especially the total lymphocyte and CD4 cell counts, during the menstrual cycle in Nigerian female subjects are relatively scarce. Aim: To determine possible changes in the total and differential white blood cell [WBC] counts, ...

  8. Production of HIV-1 by resting memory T lymphocytes

    Czech Academy of Sciences Publication Activity Database

    Gondois-Rey, F.; Biancotto, A.; Pion, M.; Chenine, A. L.; Gluschankof, P.; Hořejší, Václav; Tamalet, C.; Vigne, R.; Hirsch, I.

    2001-01-01

    Roč. 15, č. 15 (2001), s. 1931-1940 ISSN 0269-9370 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : HIV * AIDS * lymphocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.881, year: 2001

  9. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer

    DEFF Research Database (Denmark)

    Geukes Foppen, M H; Donia, M; Svane, I M

    2015-01-01

    five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. Adoptive cell therapy using tumor-infiltrating lymphocytes is yet another, but highly...

  10. Survival of human lymphocytes after exposure to densely ionizing radiations

    International Nuclear Information System (INIS)

    Madhvanath, U.; Raju, M.R.; Kelly, L.S.

    1976-01-01

    Interphase death of human blood lymphocytes cultured in vitro was studied after exposure to 60 Co gamma rays and to accelerated ions of 1 H, 4 He, 7 Li, 11 B, 12 C, 20 Ne, 40 Ar, and π - meson beam under aerobic conditions. Exposures were also conducted under hypoxic conditions with 60 Co gamma rays, 4 He, 7 Li, and 12 C ion beams. Time course of interphase death was followed for 6 days after irradiation. Percent survivals were determined by using the trypan blue exclusion method. Survival curves at 5 days postirradiation were exponential for all radiations studied. These observations indicate that the production of interphase death of lymphocytes by densely ionizing radiations follows a pattern similar to that observed with colony-forming mammalian cells. However, the reproductive capacity of the latter cells is impaired with maximum effectiveness at energy densities associated with 220 keV/μm for the beam conditions used in this investigation. The much lower energy densities required to kill a lymphocyte suggest that a sensitive structure other than DNA may be responsible for the production of lymphocyte death, perhaps the membranes. The calculated inactivation cross sections for high-LET radiations above 650 keV/μm yielded values larger than the actual cell dimensions. It appears that contributions from delta rays become appreciable in this system at these LET's

  11. Cytotoxic T-Lymphocyte Antigen-2 alpha participates in axial ...

    African Journals Online (AJOL)

    Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2α) has been discovered and expressed in mouse activated T-cells and mast cells. Structurally, it is homologous to the proregion of mouse cathepsin L, a lysosomal cystein proteinase. Expressed recombinant CTLA-2α is shown to exhibit selective inhibition to cathepsin L and ...

  12. Johnson syndrome in a Nigerian woman with chronic lymphocytic ...

    African Journals Online (AJOL)

    Stevens-Johnson syndrome is an adverse muco-cutaneous complication arising from a number of conditions which include the administration of some drugs. A female Nigerian with chronic lymphocytic leukaemia, (Binet stage C) who developed Stevens-Johnson syndrome following commencement of allopurinol is ...

  13. T lymphocyte subsets in prostate cancer subjects in south eastern ...

    African Journals Online (AJOL)

    Humoral and cellular mechanisms play roles in immune response to foreign antigens. The present study was designed to determine the T lymphocyte subsets (CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) in the prostate cancer subjects and control subjects. CD4 + T cells (`l/count) and CD8 + T cells (`l/count) were ...

  14. Immunophenotypic enumeration of CD4 + T-lymphocyte values in ...

    African Journals Online (AJOL)

    Background: The enumeration of CD4+ T-lymphocytes in Human Immunodeficiency Virus (HIV)-infected individuals is an essential tool for staging HIV disease, to make decisions for initiation of anti-retroviral therapy (ART), for monitoring response to ART and to initiate chemoprophylaxis against opportunistic infections.

  15. Standardized assessment of tumor-infiltrating lymphocytes in breast cancer

    DEFF Research Database (Denmark)

    Tramm, Trine; Di Caterino, Tina; Jylling, Anne-Marie B

    2018-01-01

    INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new...

  16. Specific depletion of mature T lymphocytes from human bone marrow

    DEFF Research Database (Denmark)

    Geisler, C; Møller, J; Plesner, T

    1989-01-01

    An effective method for specific depletion of mature T lymphocytes from human bone marrow mononuclear cells (BMMC) with preservation of prethymic T cells and natural killer (NK) cells is presented. The BMMC were incubated with F101.01, a monoclonal antibody recognizing an epitope of the T...

  17. Tumor-infiltrating lymphocytes (TILs) from patients with glioma

    DEFF Research Database (Denmark)

    Liu, Zhenjiang; Meng, Qingda; Bartek, Jiri

    2017-01-01

    Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21...

  18. Activated T lymphocytes disappear from circulation during endotoxemia in humans

    DEFF Research Database (Denmark)

    Suarez Krabbe, Karen; Kemp, Helle Bruunsgaard; Qvist, Jesper

    2002-01-01

    of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis....

  19. A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Tucker DL

    2015-06-01

    Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

  20. Bringing statistics up to speed with data in analysis of lymphocyte motility.

    Science.gov (United States)

    Letendre, Kenneth; Donnadieu, Emmanuel; Moses, Melanie E; Cannon, Judy L

    2015-01-01

    Two-photon (2P) microscopy provides immunologists with 3D video of the movement of lymphocytes in vivo. Motility parameters extracted from these videos allow detailed analysis of lymphocyte motility in lymph nodes and peripheral tissues. However, standard parametric statistical analyses such as the Student's t-test are often used incorrectly, and fail to take into account confounds introduced by the experimental methods, potentially leading to erroneous conclusions about T cell motility. Here, we compare the motility of WT T cell versus PKCθ-/-, CARMA1-/-, CCR7-/-, and PTX-treated T cells. We show that the fluorescent dyes used to label T cells have significant effects on T cell motility, and we demonstrate the use of factorial ANOVA as a statistical tool that can control for these effects. In addition, researchers often choose between the use of "cell-based" parameters by averaging multiple steps of a single cell over time (e.g. cell mean speed), or "step-based" parameters, in which all steps of a cell population (e.g. instantaneous speed) are grouped without regard for the cell track. Using mixed model ANOVA, we show that we can maintain cell-based analyses without losing the statistical power of step-based data. We find that as we use additional levels of statistical control, we can more accurately estimate the speed of T cells as they move in lymph nodes as well as measure the impact of individual signaling molecules on T cell motility. As there is increasing interest in using computational modeling to understand T cell behavior in in vivo, these quantitative measures not only give us a better determination of actual T cell movement, they may prove crucial for models to generate accurate predictions about T cell behavior.

  1. Characterization of cat dander-specific T lymphocytes from atopic patients

    NARCIS (Netherlands)

    van Neerven, R. J.; van de Pol, M. M.; van Milligen, F. J.; Jansen, H. M.; Aalberse, R. C.; Kapsenberg, M. L.

    1994-01-01

    Fel d I, the major cat dander allergen, is recognized by serum IgE of more than 80% of all cat-allergic patients. Because IgE synthesis by B lymphocytes is under the control of T lymphocytes, we studied the specificity and lymphokine production profiles of cat dander-specific T lymphocytes.

  2. Biometric indices of recirculating lymphocytes after acute and chronic gamma-irradiation

    International Nuclear Information System (INIS)

    Kalinin, E.V.

    1978-01-01

    The karyometry method was used to study the distribution of mature lymphocytes of lymphatic organs and peripheral blood among classes of nuclear volumes. Radiation injury was accompanied by a selection of populations of short-lived lymphocytes with very big nuclei the content of which was function of cumulative radiation dose. The number of small lymphocytes dependend on the phase of the radiation reaction

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

    DEFF Research Database (Denmark)

    Hagdrup, H; Tønnesen, E; Clemmensen, O

    1992-01-01

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

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

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

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

  5. Human T Lymphocytes Are Permissive for Dengue Virus Replication.

    Science.gov (United States)

    Silveira, Guilherme F; Wowk, Pryscilla F; Cataneo, Allan H D; Dos Santos, Paula F; Delgobo, Murilo; Stimamiglio, Marco A; Lo Sarzi, Maria; Thomazelli, Ana Paula F S; Conchon-Costa, Ivete; Pavanelli, Wander R; Antonelli, Lis R V; Báfica, André; Mansur, Daniel S; Dos Santos, Claudia N Duarte; Bordignon, Juliano

    2018-05-15

    Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4 + and CD8 + T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4 + and CD8 + T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4 + but not CD8 + T cells after exposure to DV in vitro Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4 + and CD8 + T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infection in vitro and in vivo , suggesting that this cell population may be a viral reservoir during the acute phase of the disease. IMPORTANCE Infection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show

  6. Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

    Science.gov (United States)

    Lee, Dooyoung; Kim, Jiyeon; Beste, Michael T; Koretzky, Gary A; Hammer, Daniel A

    2012-06-01

    T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.

  7. Nucleic Acids as Information Molecules.

    Science.gov (United States)

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  8. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.

    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update

  9. Hybrid molecule/superconductor assemblies

    International Nuclear Information System (INIS)

    McDevitt, J.T.; Haupt, S.G.; Riley, D.R.; Zhao, J.; Zhou, J.P., Jones, C.

    1993-01-01

    The fabrication of electronic devices from molecular materials has attracted much attention recently. Schottky diodes, molecular transistors, metal-insulator-semiconductor diodes, MIS field effect transistors and light emitting diodes have all been prepared utilizing such substances. The active elements in these devices have been constructed by depositing the molecular phase onto the surface of a metal, semiconductor or insulating substrate. With the recent discovery of high temperature superconductivity, new opportunities now exist for the study of molecule/superconductor interactions as well as for the construction of novel hybrid molecule/superconductor devices. In this paper, methods for preparing the initial two composite molecule/semiconductor devices will be reported. Consequently, light sensors based on dye-coated superconductor junctions as well as molecular switches fashioned from conductive polymer coated superconductor junctions as well as molecular switches fashioned from conductive polymer coated superconductor microbridges will be discussed. Moreover, molecule/superconductor energy and electron transfer phenomena will be illustrated also for the first time

  10. Mass spectrometry of large molecules

    International Nuclear Information System (INIS)

    Facchetti, S.

    1985-01-01

    The lectures in this volume were given at a course on mass spectrometry of large molecules, organized within the framework of the Training and Education programme of the Joint Research Centre of the European Communities. Although first presented in 1983, most of the lectures have since been updated by their authors. (orig.)

  11. WHAT ARE THE MOLECULES DOING?

    African Journals Online (AJOL)

    Temechegn

    University of the Witwatersrand, Johannesburg, South Africa ... [African Journal of Chemical Education—AJCE 6(2), July 2016] ... understand science concepts: in essence these are macroscopic (phenomena), microscopic .... than the simple freeing up of already-existing smaller molecules: this implies a high melting point.

  12. Fascinating Organic Molecules from Nature

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 5. Fascinating Organic Molecules from Nature - Using a Natural ... Road Banashankari 2nd Stage Bangalore 560 070, India. Department of Chemistry Sri Sathya Sai Institute of Higher Learning Brindavan Campus Bangalore 560 067, India.

  13. Fascinating Organic Molecules from Nature

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 7. Fascinating Organic Molecules from Nature - Sweet Stimulants of ... Road Banashankari 2nd Stage Bangalore 560 070, India. Department of Chemistry Sri Sathya Sai Institute of Higher Learning Brindavan Campus Bangalore 560 067, India.

  14. Multiphoton dissociation of polyatomic molecules

    International Nuclear Information System (INIS)

    Schulz, P.A.

    1979-10-01

    The dynamics of infrared multiphoton excitation and dissociation of SF 6 was investigated under collision free conditions by a crossed laser-molecular beam method. In order to understand the excitation mechanism and to elucidate the requirements of laser intensity and energy fluence, a series of experiments were carried out to measure the dissociation yield dependences on energy fluence, vibrational temperature of SF 6 , the pulse duration of the CO 2 laser and the frequency in both one and two laser experiments. Translational energy distributions of the SF 5 dissociation product measured by time of flight and angular distributions and the dissociation lifetime of excited SF 6 as inferred from the observation of secondary dissociation of SF 5 into SF 4 and F during the laser pulse suggest that the dynamics of dissociation of excited molecules is dominated by complete energy randomization and rapid intramolecular energy transfer on a nanosecond timescale, and can be adequately described by RRKM theory. An improved phenomenological model including the initial intensity dependent excitation, a rate equation describing the absorption and stimulated emission of single photons, and the unimolecular dissociation of excited molecules is constructed based on available experimental results. The model shows that the energy fluence of the laser determines the excitation of molecules in the quasi-continuum and the excess energy with which molecules dissociate after the laser pulse. The role played by the laser intensity in multiphoton dissociation is more significant than just that of overcoming the intensity dependent absorption in the lowest levels. 63 references

  15. Cytogenetic effect of 153 Sm-EDTMP in peripheral lymphocytes of patients with metastatic cancer

    International Nuclear Information System (INIS)

    Silva, Marcia Augusta da

    2001-01-01

    The 153 Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of 153 Sm-EDTMP at cellular level. The present study was conduced with the aim of evaluating the cytogenetic effects of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique, either in vivo or in vitro. For that, the blood samples were collected before and one hour after the endovenous administration of 153 Sm-EDTMP (mean activity of 42.53+/-5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before 153 Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with 153 Sm-EDTMP, did not influence these parameters. The carrier molecule, EDTMP, did not influence the induction of chromosome aberration. In relation to the in vitro assays, the obtained data of peripheral lymphocytes of healthy donors and patients with no previous treatment exposed to different radioactive concentration of 153 Sm-EDTMP (0.046 - 1.110 MBq/mL) were better adjusted by linear regression model (Y=A+BX). The chromosome damage induced by 153 Sm-EDTMP observed in vitro was about 2 fold higher than that found in vivo for the group of patients with no previous treatment. The obtained data showed that the therapy with 153 Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes on hour after its administration in

  16. Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung cancer

    International Nuclear Information System (INIS)

    Nakayama, Yasuhiro; Makino, Shigeki; Fukuda, Yasuki; Min, Kyong-Yob; Shimizu, Akira; Ohsawa, Nakaaki

    1996-01-01

    Purpose: Radiation pneumonitis sometimes extends beyond the irradiated area of a lung and can also affect the opposite lung. Some immunological mechanisms, in addition to simple direct injury of the lungs by radiation, seem to be involved in the onset of radiation pneumonitis. To clarify such mechanisms, the effects of radiation on local inflammatory cells in lungs, in particular, lymphocytes, were examined. Methods and Materials: A comparison was made of bronchoalveolar lavage fluid (BALF) findings from 13 irradiated patients (RT group) and 15 nonirradiated patients (non-RT group) with lung cancer. Patients who later developed radiation pneumonitis (RP group) and those who did not (RP-free group) were also compared. Using a two-color flowcytometer, radiation-induced changes in local inflammatory cells in lungs were analyzed. This included analyses of human leukocyte-associated antigen (HLADR) and intercellular adhesion molecule-1 (ICAM-1) expression on T-cells, which are thought to be involved in cell activation and interactions between cells. Results: The following aspects of BALF were higher in the RT group than in the non-RT group: (a) the percentage of lymphocytes and eosinophiles; (b) the incidence of HLADR-positive CD4+T-cells and HLADR-positive CD8+T-cells; and (c) the incidence of ICAM-1-positive T-cells. The following aspects of BALF were higher in the RP group than in the RP-free group: (a) the total cell counts; (b) the percentage of lymphocytes; and (c) the incidence of ICAM-1-positive T-cells. A significant relationship was seen between the incidence of ICAM-1 expression on T-cells and the number of days from the initiation of radiotherapy to the onset of radiation pneumonitis. Conclusion: These data suggest that irradiation can induce accumulation of activated T-cells (HLADR and ICAM-1-positive T-cells) in the lung. This accumulation may be closely linked to radiation-induced lung injury. It is also suggested that the incidence of ICAM-1-positive T

  17. Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.

    Science.gov (United States)

    Haller, H; Ziegler, E M; Homuth, V; Drab, M; Eichhorn, J; Nagy, Z; Busjahn, A; Vetter, K; Luft, F C

    1997-01-01

    Endothelial cell activation is important in the pathogenesis of preeclampsia; however, the nature of the activation is unknown. We investigated 22 patients with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptic patients induces expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured endothelial cells. We then asked whether the corresponding integrin adhesive counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18), macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the pregnant women, the measurements were conducted both before and after delivery. Integrin expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum from preeclamptic patients increased endothelial cell ICAM-1 expression but not VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in endothelial cells compared with serum from normal nonpregnant or normal pregnant women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1 expression in preeclamptic patients (r = .80, P preclampsia and normal pregnancy compared with the nonpregnant state. The expression decreased significantly after delivery in both groups. Our results demonstrate that serum from preeclamptic women induces increased ICAM-1 surface expression on endothelial cells, while the expression of the integrin counterreceptors was not different. The effect on endothelial cells may be related to an increase in [Ca2+]i. The effect on cultured endothelial cells and the rapid decrease after delivery suggests the presence of a circulating serum

  18. Cosmic radiation induced chromosomal aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    De Angelis, G.; Facius, R.; Reitz, G.

    2003-01-01

    Since decades, elevated frequencies of dicentric chromosomes (DIC) in human lymphocytes have successfully been used as a biological dosimeter in cases of acute, often accidental exposures to ionizing radiation. As long as duration and time lags after exposure are small compared to the lifetime of DIC, their frequencies can also be used to assess doses from protracted, chronic irradiation. E.g., within the substantial range of uncertainties, the frequencies of DIC observed in cosmonauts are compatible with the frequencies expected from doses of low and high LET radiation to which they were exposed in low earth orbit (LEO). On the other hand, frequencies of DIC detected in lymphocytes of civilian aviation crewmembers rarely correlate with the doses accumulated all along their professional career. For such long duration exposures with relatively low induction rates, the concomitant decay of DIC frequencies due to the removal during exposure of lymphocytes carrying DIC has to be taken into account. We present temporal profiles of frequencies of DIC during the exposure calculated with a model of exponential decay of DIC for some scenarios of chronic exposure to cosmic radiation. E.g., even after a 'heavily' shielded Mars mission, the expected frequencies of DIC in lymphocytes of astronauts will be 10 to 40 times higher than the terrestrial control levels. For air flight personnel we calculated the time profiles of frequencies of DIC in lymphocytes of a 'typical' pilot, a male cabin attendant and a female cabin attendant whose professional radiation exposures were recalculated for the actual flight routes flown during their entire flight career as recorded in detailed duty logs. These results demonstrate that experimental (epidemiological) studies concerning DIC in air or space flight personnel must explicitly take into consideration the temporal exposure profiles in the prospective study population and that the point in time at which blood samples are to be drawn must

  19. Psychological stress during exercise: lymphocyte subset redistribution in firefighters.

    Science.gov (United States)

    Huang, Chun-Jung; Webb, Heather E; Garten, Ryan S; Kamimori, Gary H; Acevedo, Edmund O

    2010-10-05

    The purpose of this study examined the changes in heart rate (HR), catecholamines (NE, EPI) and percentages of blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, CD3- CD56+ NK cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes [NK cells+T cells+B cells]) in firefighters exposed to a computerized firefighting strategies and tactics decision-making challenge while participating in moderate intensity exercise. Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and blood lymphocyte subsets following combined mental and physical challenge. Ten professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37min of cycle ergometry at 60% VO(2max) (exercise alone condition; EAC) and (2) 37min of cycle ergometry at 60% VO(2max) along with 20min of a computerized firefighting strategies and tactics decision-making challenge (firefighting strategies condition; FSC). FSC elicited significantly greater HR, NE, and EPI when compared to EAC. Both EAC and FSC elicited increases in CD3- CD56+ NK cells. The percentages of CD3+ T cells, CD3+CD4+ helper T cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes were lower immediately following both conditions. Following dual challenge NE AUC was negatively correlated with percentage of CD19+ B cells immediately post challenge, and HR was negatively associated with the percent change in the CD4/CD8 ratio from pre to post challenge. These elevations in NE and heart rate simultaneously in response to the dual challenge suggest greater sympathetic activation that in turn would possibly explain the alteration in the distribution of lymphocyte subsets. Published by Elsevier Inc.

  20. Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Arshed Nazmi

    2018-03-01

    Full Text Available BackgroundPeriventricular leukomalacia (PVL is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured hemisphere compared to the contralateral (control, uninjured hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.

  1. Lymphocytic Colitis: Pathologic predictors of response to therapy.

    Science.gov (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

    2018-02-13

    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  2. Isotope separation using vibrationally excited molecules

    International Nuclear Information System (INIS)

    Woodroffe, J.A.; Keck, J.C.

    1979-01-01

    Vibrational excitation of molecules having components of a selected isotope type is used to produce a conversion from vibrational to translational excitation of the molecules by collision with the molecules of a heavy carrier gas. The resulting difference in translaton between the molecules of the selected isotope type and all other molecules of the same compound permits their separate collection. When applied to uranium enrichment, a subsonic cryogenic flow of molecules of uranium hexafluoride in combination with an argon carrier gas is directed through a cooled chamber that is illuminated by laser radiaton tuned to vibrationally excite the uranium hexafluoride molecules of a specific uranium isotope. The excited molecules collide with carrier gas molecules, causing a conversion of the excitation energy into a translation of the excited molecule, which results in a higher thermal energy or diffusivity than that of the other uranium hexafluoride molecules. The flowing molecules including the excited molecules directly enter a set of cryogenically cooled channels. The higher thermal velocity of the excited molecules increases the probability of their striking a collector surface. The molecules which strike this surface immediately condense. After a predetermined thickness of molecules is collected on the surface, the flow of uranium hexafluoride is interrupted and the chamber heated to the point of vaporization of the collected hexafluoride, permitting its removal. (LL)

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

    Directory of Open Access Journals (Sweden)

    Bernadete L. Liphaus

    2006-01-01

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

  4. Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

    International Nuclear Information System (INIS)

    Goodman, M.G.; Fidler, J.M.; Weigle, W.O.

    1978-01-01

    The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

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

    Directory of Open Access Journals (Sweden)

    Sargın MA

    2016-04-01

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

  6. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Yazar

    2015-11-01

    Full Text Available Acute appendicitis (AA is not uncommon during pregnancy but can be difficult to diagnose. This study evaluated the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR in addition to conventional diagnostic indicators of the disease to diagnose AA during pregnancy. Age, gestational age, white blood cell (WBC count, Alvarado scores, C-reactive protein (CRP, lymphocyte count, NLR and PLR were compared among 28 pregnant women who underwent surgery for AA, 35 pregnant women wrongly suspected as having AA, 29 healthy pregnant women, and 30 nonpregnant healthy women. Mean WBC counts and CRP levels were higher in women with proven AA than in those of control groups (all p < 0.05. Among all the groups, the median NLR and PLR were significantly different in women with proven AA (all p < 0.05. Receiver operating characteristic analysis was used to determine cut-off values for WBC count, CRP, lymphocyte count, NLR and PLR, and multiple logistic regression analysis showed that NLR and PLR used with routine methods could diagnose AA with 90.5% accuracy. Used in addition to routine diagnostic methods, NLR and PLR increased the accuracy of the diagnosis of AA in pregnant women.

  7. Preparation of translationally cold neutral molecules.

    Science.gov (United States)

    Di Domenicantonio, Giulia; Bertsche, Benjamin; Osterwalder, Andreas

    2011-01-01

    Efforts at EPFL to obtain translationally cold neutral molecules are described. Active deceleration of polar molecules is performed by confining the molecules in moving three-dimensional electrostatic traps, and by appropriately choosing the velocity of those traps. Alternatively, cold molecules can be obtained by velocity filtering. Here, the velocity of the molecules is not changed, but instead the cold molecules are extracted from a thermal sample by using the competition between the electrostatic force and the centrifugal force inside a bent electrostatic guide for polar molecules.

  8. Changes in blood lymphocyte subpopulations and expression of MHC-II molecules in wild mares before and after parturition

    Directory of Open Access Journals (Sweden)

    Krakowski Leszek

    2017-06-01

    Full Text Available Introduction: Pregnancy is a physiological state in which the immune system undergoes certain changes. On the one hand, by depleting cell defence mechanisms, it favours development and maintenance of the pregnancy. At the same time cells of the immune system ensure resistance to many risk factors, including infectious agents.

  9. Expression of costimulatory molecules in the bovine corpus luteum

    Directory of Open Access Journals (Sweden)

    Pate Joy L

    2007-01-01

    Full Text Available Abstract Background Bovine luteal parenchymal cells express class II major histocompatibility complex (MHC molecules and stimulate class II MHC-dependent activation of T cells in vitro. The ability of a class II MHC-expressing cell type to elicit a response from T cells in vivo is also dependent on expression of costimulatory molecules by the antigen presenting cell and delivery of a costimulatory signal to the T cell. Whether bovine luteal parenchymal cells express costimulatory molecules and can deliver the costimulatory signal is currently unknown. Methods Bovine luteal tissue was collected during the early (day 5; day of estrus = day 0, mid (day 11–12, or late (day 18 luteal phase of the estrous cycle, and at 0, 0.5, 1, 4, 12 or 24 hours following administration of PGF2alpha to cows on day 10 of the estrous cycle. Northern analysis was used to measure CD80 or CD86 mRNA concentrations in luteal tissue samples. Mixed luteal parenchymal cell cultures and purified luteal endothelial cell cultures were prepared, and real-time RT-PCR was used to examine the presence of CD80 and CD86 mRNA in each culture type. Monoclonal antibodies to CD80 and CD86 were added to a mixed luteal parenchymal cell-T cell co-culture in vitro T cell proliferation assay to assess the functional significance of costimulatory molecules on activation of T lymphocytes by luteal parenchymal cells. Results Northern analysis revealed CD80 and CD86 mRNAs in luteal tissue, with greatest steady-state concentrations at midcycle. CD80 and CD86 mRNAs were detected in mixed luteal parenchymal cell cultures, but only slight amounts of CD80 (and not CD86 mRNA were detected in cultures of luteal endothelial cells. Luteinizing hormone, PGF2alpha and TNF-alpha were without effect on concentrations of CD80 or CD86 mRNA in mixed luteal parenchymal cells cultures. Anti-CD80 or anti-CD86 monoclonal antibodies inhibited T cell proliferation in the in vitro T cell proliferation assay

  10. Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

    DEFF Research Database (Denmark)

    Werdelin, O; Mouritsen, S; Petersen, B L

    1988-01-01

    The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic...... fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC...... molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has...

  11. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-01-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  12. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    Energy Technology Data Exchange (ETDEWEB)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-11-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  13. The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

    International Nuclear Information System (INIS)

    Yang Huibin

    1989-01-01

    The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

  14. Observing electron motion in molecules

    International Nuclear Information System (INIS)

    Chelkowski, S; Yudin, G L; Bandrauk, A D

    2006-01-01

    We study analytically the possibility for monitoring electron motion in a molecule using two ultrashort laser pulses. The first prepares a coherent superposition of two electronic molecular states whereas the second (attosecond pulse) photoionizes the molecule. We show that interesting information about electron dynamics can be obtained from measurement of the photoelectron spectra as a function of the time delay between two pulses. In particular, asymmetries in photoelectron angular distribution provide a simple signature of the electron motion within the initial time-dependent coherently coupled two molecular states. Both asymmetries and electron spectra show very strong two-centre interference patterns. We illustrate these effects using as an example a dissociating hydrogen molecular ion probed by the attosecond pulses

  15. Tunneling Ionization of Diatomic Molecules

    DEFF Research Database (Denmark)

    Svensmark, Jens Søren Sieg

    2016-01-01

    When a molecule is subject to a strong laser field, there is a probability that an electron can escape, even though the electrons are bound by a large potential barrier. This is possible because electrons are quantum mechanical in nature, and they are therefore able to tunnel through potential...... barriers, an ability classical particles do not possess. Tunnelling is a fundamental quantum mechanical process, a process that is distinctly non-classical, so solving this tunnelling problem is not only relevant for molecular physics, but also for quantum theory in general. In this dissertation the theory...... of tunneling ionizaion of molecules is presented and the results of numerical calculations are shown. One perhaps surprising result is, that the frequently used Born-Oppenheimer approximation breaks down for weak fields when describing tunneling ionization. An analytic theory applicable in the weak-field limit...

  16. Physics of atoms and molecules

    International Nuclear Information System (INIS)

    Bransden, B.H.; Joachain, C.J.

    1983-01-01

    This book presents a unified account of the physics of atoms and molecules at a level suitable for second- and third-year undergraduate students of physics and physical chemistry. Following a brief historical introduction to the subject the authors outline the ideas and approximation methods of quantum mechanics to be used later in the book. Six chapters look at the structure of atoms and the interactions between atoms and electromagnetic radiation. The authors then move on to describe the structure of molecules and molecular spectra. Three chapters deal with atomic collisions, the scattering of electrons by atoms and the scattering of atoms by atoms. The concluding chapter considers a few of the many important applications of atomic physics within astrophysics, laser technology, and nuclear fusion. Problems are given at the end of each chapter, with hints at the solutions in an appendix. Other appendices include various special topics and derivations together with useful tables of units. (author)

  17. γδ T LYMPHOCYTES AS A FIRST LINE OF IMMUNE DEFENSE: OLD AND NEW WAYS OF ANTIGEN RECOGNITION AND IMPLICATIONS FOR CANCER IMMUNOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Maria Raffaella eZocchi

    2014-11-01

    Full Text Available Among γδT cells, the Vδ1 subset, resident in epithelial tissues, is implied in the defense against viruses, fungi and certain hematological malignancies, while the circulating Vδ2 subpopulation mainly respond to mycobacteria and solid tumors. Both subsets can be activated by stress-induced molecules (MIC-A, MIC-B, ULBPs to produce pro-inflammatory cytokines and lytic enzymes and destroy bacteria or damaged cells. γδT lymphocytes can also recognize lipids, as those associated to M. tuberculosis, presented by the CD1 molecule, or phosphoantigens (P-Ag, either autologous, which accumulates in virus-infected cells, or microbial produced by prokaryotes and parasites. In cancer cells P-Ag accumulate due to alterations in the mevalonate pathway; recently, butyrophilin 3A1 has been shown to be the presenting molecule for P-Ag. Of interest, aminobisphosphonates indirectly activate Vδ2 T cells inducing the accumulation of P-Ag. Based on these data, γδT lymphocytes are attractive effectors for cancer immunotherapy. However, the results obtained in clinical trials so far have been disappointing: this review will focus on the possible reasons of this failure as well as on suggestions for implementation of the therapeutic strategies.

  18. Electrondriven processes in polyatomic molecules

    Energy Technology Data Exchange (ETDEWEB)

    McKoy, Vincent [California Inst. of Technology (CalTech), Pasadena, CA (United States)

    2017-03-20

    This project developed and applied scalable computational methods to obtain information about low-energy electron collisions with larger polyatomic molecules. Such collisions are important in modeling radiation damage to living systems, in spark ignition and combustion, and in plasma processing of materials. The focus of the project was to develop efficient methods that could be used to obtain both fundamental scientific insights and data of practical value to applications.

  19. Intersystem crossing in complex molecules

    International Nuclear Information System (INIS)

    Pappalardo, R.G.

    1980-01-01

    The general question of singlet-triplet intersystem crossing is addressed in the context of large organic molecules, i.e., ''complex'' molecules capable of self-relaxation in the absence of collisions. Examples of spectral properties of such molecules in the vapor phase are discussed, relying on extensive Russian literature in this area. Formal expressions for the relaxation rate in the electronic excited states are derived on the basis of the formalism of collision theory, and are applied to the specific case of intersystem crossing. The derivation of the ''energy-gap'' law for triplet-singlet conversion in aromatic hydrocarbons is briefly outlined. The steep rise of internal conversion rates as a function of excess excitation energy, and its competition with the intersystem crossing process, are reviewed for the case of naphthalene vapor. A general expression for the spin-orbit interaction Hamiltonian in molecular systems is outlined. Experimental observations on singlet-triplet conversion rates and the factors that can drastically affect such rates are discussed, with emphasis on the ''in- ternal'' and ''external'' heavy-atom effects. Basic relations of ESR spectroscopy and magnetophotoselection are reviewed. Technological implications of the singlet-triplet crossing in complex molecules are discussed in the context of chelate lasers, dye lasers and luminescent displays. Effects related to singlet-triplet crossing, and generally to excited-state energy-transfer in biological systems, are exemplified by the role of aromatic amino-acids in the phosphorescence of proteins, by some recent studies of energy-transfer in models of biomembranes, and by the clustering of triplet-energy donor-acceptor pairs in micelles

  20. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  1. Electron interactions with polar molecules

    International Nuclear Information System (INIS)

    Garrett, W.R.

    1981-01-01

    A description is given of a number of the features of discrete and continuous spectra of electrons interacting with polar molecules. Attention is focused on the extent to which theoretical predictions concerning cross sections, resonances, and bound states are strongly influenced by the various approximations that are so ubiquitous in the treatment of such problems. Similarly, threshold scattering and photodetachment processes are examined for the case of weakly bound dipole states whose higher members overlap the continuum

  2. Atg5 Is Essential for the Development and Survival of Innate Lymphocytes

    Directory of Open Access Journals (Sweden)

    Timothy E. O’Sullivan

    2016-05-01

    Full Text Available Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK cells and group 1, 2, and 3 innate ILCs. Although inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia.

  3. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...... thymic activity and diminished numbers of T lymphocytes in peripheral lymphoid tissues. The total number of cells in these tissues as well as the blast cell activity, were within normal limits. Bone marrow lymphocyte numbers and kinetics as well as blood lymphocyte levels in splenectomized and sham......-splenectomized normal animals were comparable. Blood lymphocyte numbers were at normal levels in splenectomized nude mice, in spite of reduced numbers of bone marrow and thoracic duct lymphocytes. It is suggested that increased number of newly-formed lymphocytes, found in lymph nodes and blood of splenectomized mice...

  4. A single-molecule diode

    Science.gov (United States)

    Elbing, Mark; Ochs, Rolf; Koentopp, Max; Fischer, Matthias; von Hänisch, Carsten; Weigend, Florian; Evers, Ferdinand; Weber, Heiko B.; Mayor, Marcel

    2005-01-01

    We have designed and synthesized a molecular rod that consists of two weakly coupled electronic π -systems with mutually shifted energy levels. The asymmetry thus implied manifests itself in a current–voltage characteristic with pronounced dependence on the sign of the bias voltage, which makes the molecule a prototype for a molecular diode. The individual molecules were immobilized by sulfur–gold bonds between both electrodes of a mechanically controlled break junction, and their electronic transport properties have been investigated. The results indeed show diode-like current–voltage characteristics. In contrast to that, control experiments with symmetric molecular rods consisting of two identical π -systems did not show significant asymmetries in the transport properties. To investigate the underlying transport mechanism, phenomenological arguments are combined with calculations based on density functional theory. The theoretical analysis suggests that the bias dependence of the polarizability of the molecule feeds back into the current leading to an asymmetric shape of the current–voltage characteristics, similar to the phenomena in a semiconductor diode. PMID:15956208

  5. The largest molecules in space

    International Nuclear Information System (INIS)

    Greenberg, J.M.

    1983-01-01

    The bulk of complex molecules in the space between the stars is shown to be in the small frozen particles of interstellar dust. Each dust grain typically contains some 10 9 atoms of oxygen, carbon and nitrogen in an amorphous molecular mixture. As a result of chemical processing of the particles by ultraviolet photons over times spanning proportional10 8 -10 9 years a substantial portion of each dust grain is converted into complex organic molecules whose maximum molecular weight is limited only by the size of the grain. Laboratory studies of evolution of analog grain materials shows that molecular weights of the order of 500 are readily created and that there is an excellent probability of much more complex molecules being produced. The organic dust component constitutes about one tenth of a percent of the total mass of the Milky Way and far outweighs any estimates of the total mass of all the planets. A planet like the earth is continually accreting matter from space and there was a high probability that in the first five hundred million years after its crust formed it passed through several dark clouds and accreted from a hundred million to ten thousand million tonnes of the organic material of the interstellar dust during each passage. It is suggested that this rain of material could have provided the molecular templates for the origin of life. (orig.)

  6. Electric moments in molecule interferometry

    International Nuclear Information System (INIS)

    Eibenberger, Sandra; Gerlich, Stefan; Arndt, Markus; Tuexen, Jens; Mayor, Marcel

    2011-01-01

    We investigate the influence of different electric moments on the shift and dephasing of molecules in a matter wave interferometer. Firstly, we provide a quantitative comparison of two molecules that are non-polar yet polarizable in their thermal ground state and that differ in their stiffness and response to thermal excitations. While C 25 H 20 is rather rigid, its larger derivative C 49 H 16 F 52 is additionally equipped with floppy side chains and vibrationally activated dipole moment variations. Secondly, we elucidate the role of a permanent electric dipole momentby contrasting the quantum interference pattern of a (nearly) non-polar and a polar porphyrin derivative. We find that a high molecular polarizability and even sizeable dipole moment fluctuations are still well compatible with high-contrast quantum interference fringes. The presence of permanent electric dipole moments, however, can lead to a dephasing and rapid degradation of the quantum fringe pattern already at moderate electric fields. This finding is of high relevance for coherence experiments with large organic molecules, which are generally equipped with strong electric moments.

  7. Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

    DEFF Research Database (Denmark)

    Holland, J; Owens, T

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...... cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we...... investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase...

  8. Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade.

    Science.gov (United States)

    Dejaegher, Joost; Verschuere, Tina; Vercalsteren, Ellen; Boon, Louis; Cremer, Jonathan; Sciot, Raf; Van Gool, Stefaan W; De Vleeschouwer, Steven

    2017-11-01

    Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. © 2017 UICC.

  9. Radioprotective effect of methanolic root extract of Loeseneriella arnottiana on radiation induced DNA damage in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Prajna, P.S.

    2012-01-01

    Intense exposure to ionization radiation by accidental, occupational or therapeutical purpose causes cellular damage mainly by formation of excessive reactive oxygen species (ROS) or by free radicals. Humans are intentionally exposed to ionising radiation for diagnostic or therapeutic purposes. The use of ionising radiation in cancer therapy may lead to transient and/or permanent injury to normal tissues within the treatment field. To increase the therapeutic index of radiation therapy, various modes of radioprotection have been developed that selectively reduce cytotoxic effects to normal tissues. Because radiation-induced cellular damage is attributed primarily to the harmful effects of free radicals, molecules with radical scavenging properties are particularly promising as radioprotectors. Loeseneriella arnottiana, a member of family Hippocrateaceae, is a climbing shrub used by traditional medicine practitioners. To study the antioxidant activity and radioprotective effect of methanolic root extract of Loeseneriella arnottiana against electron beam radiation induced DNA damage in human lymphocytes. Loeseneriella arnottiana roots were dried and extracted using methanol by solvent extraction method. Antioxidant activity was measured by DPPH method. DNA damage was assessed by comet assay parameters. The lymphocytes were incubated for one hour with two different concentrations 10 μg and 50 μg of root extract before exposure to 2 Gy electron beam radiation. 30 μg of methanolic root extract of Loeseneriella arnottiana exhibited 96% radical scavenging activity comparable to 15 μg of ascorbic acid. In reducing power assay it showed dose dependent increase in absorbance indicating that extract is capable of donating hydrogen atoms. Pretreatment of lymphocytes with 10 μg and 50 μg of root extract before irradiation resulted in reduction in the Comet length, Olive tail moment, percentage of DNA in tail when compared to the radiation control group. Results of this

  10. Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

    Directory of Open Access Journals (Sweden)

    Diego Marcos-Pérez

    2018-05-01

    Full Text Available Frailty denotes a multidimensional syndrome that gives rise to vulnerability to stressors and leads to an increase of the age-related decline of different physiological systems and cognitive abilities. Aging-related alterations of the immune system may compromise its competence culminating in a chronic low-grade inflammation state. Thus, it has been proposed that frailty is associated with alterations in the concentration of pro-inflammatory molecules and in different lymphocyte subpopulations. To provide further support to the validity of that hypothesis, we conducted a cross-sectional study in a population of Spanish older adults (N = 259, aged 65 and over classified according to their frailty status. Biomarkers analyzed included percentages of several lymphocyte subsets and several inflammation mediators, namely concentrations of interleukin 6 (IL6, C-reactive protein (CRP, tumor necrosis factor α (TNFα, and 75 kDa soluble TNFα receptor II (sTNF-RII. Reference ranges for the inflammation mediators were established for the first time in robust older adults. A significant increase in the CD4+/CD8+ ratio and a significant decrease in the % CD19+ cells were observed in the frail group. Progressive increases with frailty severity were obtained in all inflammatory mediator concentrations, especially notable for IL6 and sTNF-RII. Area under the receiver-operating characteristic curve obtained for sTNF-RII (0.90, 95% CI 0.85–0.94, P < 0.001 indicates a high accuracy in the predictive value of this biomarker for frailty. Although results from the current study revealed limited strength associations between frailty and the lymphocyte subsets assessed, data obtained for the inflammatory mediators provide further support to involvement of inflammaging in frailty status in older adults.

  11. Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Chang, Cheng-Shyong; Chang, Julia H; Hsu, Nicholas C; Lin, Hsuan-Yu; Chung, Chih-Yuan

    2007-01-01

    B7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC). Expression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients. CD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients. Expression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC

  12. Organ distribution of 111In-oxine labeled lymphocytes in normal subjects and in patients with chronic lymphocytic leukemia and malignant lymphoma

    International Nuclear Information System (INIS)

    Matsuda, Shin; Uchida, Tatsumi; Yui, Tokuo; Kariyone, Shigeo

    1982-01-01

    T and B lymphocyte survival and organ distribution were studied by using 111 In-oxine labeled autologous lymphocytes in 3 normal subjects, 3 patients with chronic lymphocytic leukemia (CLL) and 9 with malignant lymphoma (ML).FDisappearance curves of the labeled lymphocytes showed two exponential components in all cases. The half time of the first component was within 1 hour in all cases. That of the second one was 50.7 +- 6.4 hours for all lymphocytes, 52.0 +- 5.5 hours for T lymphocytes and 31.6 +- 4.9 hours for B lymphocytes in normal subjects, 192.6 hours for T-CLL and 57.7 +- 46.9 hours for B-CLL, and 60.2 +- 30.7 hours for T cell type of malignant lymphoma (T-ML) and 63.7 +- 24.5 hours for B cell type of malignant lymphoma (B-ML). These data might suggest that all lymphocyte disappearance curve reflected T lymphocyte disappearance curve chiefly, and the half time of B lymphocytes was shorter than that of T lymphocytes. In the T-CLL, the half time of the second component prolonged extremely in comparison with that of normal T lymphocytes. The labeled cells were accumulated in the lungs, spleen and liver immediately after the infusion, then in the spleen most remarkably 1 hour after the infusion in all cases. The radioactivity over the bone marrow was observed from 1 hour in all cases and that of lymph nodes were first noticed 18 hours after the infusion in T-CLL and T-ML, 68 hours in B-CLL but were not noticed in normal subjects and B-ML. The recovery of labeled cells in the blood was 28.5 +- 7.9% for all lymphocytes, 19.7 +- 1.9% for T lymphocytes and 11.0 +- 5.1% for B lymphocytes in normal subjects, 25.8 +- 1.6% for CLL, and 17.6 +- 11.0% for T-ML, 7.7 +- 5.2% for B-ML, respectively. (J.P.N.)

  13. Differentiation of human lymphocytes into nuclear vlimata by meiosis. The cytotoxic effect of calcium-activated neutral proteinase inhibitor

    OpenAIRE

    Logothetou-Rella, H.

    1994-01-01

    Phytohaemagglutinin (PHA)-activated lymphocytes differentiated into nuclear vlimata (NVs) in vitro. Lymphocyte attachment was followed by formation and extrusion of cytoplasmic vesicles. nuclear elongation and fragmentation into NVs. NVs and cytoplasmic vesicles were detached and organized into large cell nodules in suspension. Immunocytochemistry showed that T-lymphocytes differentiated mainly to NVs while B-lymphocytes to buds. During differentiation ther...

  14. Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.

    OpenAIRE

    Kanaly, S T; Hines, S A; Palmer, G H

    1993-01-01

    Pulmonary clearance of Rhodococcus equi requires functional T lymphocytes. In this study, CD8+ T-lymphocyte-deficient transgenic mice cleared virulent R. equi from the lungs while infection in CD4+ T-lymphocyte-deficient transgenic mice persisted. Although both CD4+ and CD8+ T cells function early in pulmonary defense against R. equi, clearance is dependent on CD4+ T lymphocytes.

  15. Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa.

    Science.gov (United States)

    Coll-Vinent, B; Cebrián, M; Cid, M C; Font, C; Esparza, J; Juan, M; Yagüe, J; Urbano-Márquez, A; Grau, J M

    1998-03-01

    To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

  16. Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lavin, M.F.; Jennings, P.A.; Hughes, D.J. (Queensland Univ., Brisbane (Australia))

    1982-05-01

    Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds.

  17. Enterocolic lymphocytic phlebitis: clinicopathologic features and review of the literature.

    Science.gov (United States)

    Ngo, Nyethane; Chang, Fuju

    2007-07-01

    Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.

  18. Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

    International Nuclear Information System (INIS)

    Lavin, M.F.; Jennings, P.A.; Hughes, D.J.

    1982-01-01

    Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds. (author)

  19. The study of lymphocytes glucocorticoid receptor in severe head injury

    International Nuclear Information System (INIS)

    Li Dapei; Wang Haodan; Zhao Qihuang

    1994-01-01

    Glucocorticoid receptors (GCR) of peripheral lymphocytes from 14 patients with severe head injury and 11 normal volunteers are studied by means of single point method of radioligand binding assay. All these patients receive surgical therapy and glucocorticoid of routine dosage. The results show that the GCR level of these patients is lower than that of the normal, while the plasma cortisol level is much higher. These changes correlate closely to the patients' clinical outcome. It is indicated that the GCR level can reflect the degree of stress of these patients and their response to glucocorticoid therapy. Using peripheral lymphocytes instead of the brain biopsy for the measurement of GCR can reflect the GCR changes of brain tissue, it's more convenient to get the sample and more acceptable to the patients

  20. UDS in lymphocytes of occupationally radiation exposed persons

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.

    1982-01-01

    To determine a possible effect of low dose radiation on DNA repair processes, peripheral lymphocytes of mine workers exposed to 222 Rn in the thermal gallery of Badgastein (Austria) and employees of the Austrian Research Centre Seibersdorf, exposed to varying doses of gamma radiation, were investigated. The capacity for unscheduled DNA synthesis (UDS) induced by in vitro UV irradiation was measured by autoradiography of isolated lymphocytes of exposed persons and unexposed controls. In all 222 Rn-exposed mine workers a significant increase of UDS above control values could be observed. Gamma irradiation 31 mrad had a significant effect on UDS, indicating a stimulation of DNA repair capability by chronic low dose exposure. (Author)