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Sample records for lymphocytic leukemia-a comparative

  1. Comparable Efficacy of Idelalisib Plus Rituximab and Ibrutinib in Relapsed/refractory Chronic Lymphocytic Leukemia: A Retrospective Case Matched Study of the Polish Adult Leukemia Group (PALG).

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    Puła, Bartosz; Budziszewska, Bożena Katarzyna; Rybka, Justyna; Gil, Lidia; Subocz, Edyta; Długosz-Danecka, Monika; Zawirska, Daria; Waszczuk-Gajda, Anna; Iskierka-Jażdżewska, Elżbieta; Kopacz, Agnieszka; Szymczyk, Agnieszka; Czyż, Jarosław; Lech-Marańda, Ewa; Warzocha, Krzysztof; Jamroziak, Krzysztof

    2018-05-01

    There is limited amount of data available on the comparative efficacy of ibrutinib and idelalisib, the B-cell receptor inhibitors (BCRi) newly approved for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) treatment. The aim of our study was to analyze and compare the outcomes of real-world r/r CLL/SLL patients treated with these two BCRi in outside clinical trials. A comparative case matched 1:2 analysis was performed on idelalisib combined with rituximab and ibrutinib efficacy in 102 patients with r/r CLL/SLL from two observational studies of the Polish Adult Leukemia Group (PALG). Both therapies produced similar overall response rates (idelalisib plus rituximab 76.4% and ibrutinib 72.1%). Median progression-free survival (PFS) and overall survival (OS) in both groups were not reached. Furthermore, no significant difference was observed between both BCRi regimens in regard to PFS (HR=0.75, 95% CI=0.30-1.86, p=0.55) and OS (HR=0.65, 95%CI=0.26-1.68, p=0.39). In summary, the results of this retrospective analysis suggest that idelalisib combined with rituximab and ibrutinib therapies have comparable activity in r/r CLL/SLL in daily clinical practice. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia--a comparative study of four differently designed, high resolution microarray platforms

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    Gunnarsson, R.; Staaf, J.; Jansson, M.

    2008-01-01

    Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K)...

  3. BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future

    NARCIS (Netherlands)

    Spaargaren, M.; de Rooij, M. F. M.; Kater, A. P.; Eldering, E.

    2015-01-01

    The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise. Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK), has received widespread

  4. New insights into hematopoietic stem cell transplantation for chronic lymphocytic leukemia: a 2015 perspective.

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    McClanahan, Fabienne; Gribben, John

    2015-09-01

    A considerable body of evidence demonstrates that allogeneic hematopoietic stem cell transplantation (HSCT) offers the only potentially curative treatment option for patients with chronic lymphocytic leukemia (CLL). However, this approach is suitable for only a minority of CLL patients, owing to its significant treatment-related mortality and morbidity. Until recently, internationally accepted guidelines suggested that HSCT should be considered in physically fit CLL patients who carry poor-risk features, such as TP53 abnormalities, or who had a short response to previous immunochemotherapy. However, several new agents and alternative treatment strategies are available that demonstrate impressive and durable responses, even in CLL patients who previously might have been candidates for transplant. The decision about which patients merit HSCT therefore remains important, and HSCT must now be considered in light of other less toxic therapies. Until data on the long-term efficacy of novel treatment approaches mature, the choice of HSCT vs alternative strategies must be assessed on a patient-by-patient basis, and treatment in the setting of randomized clinical trials should be pursued whenever possible.

  5. Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

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    Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

    2018-03-11

    Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

  6. Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review.

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    van Tilburg, C M; Sanders, E A M; Rovers, M M; Wolfs, T F W; Bierings, M B

    2006-10-01

    Intensified chemotherapy regimens resulting in improved survival of children with acute lymphocytic leukemia (ALL) lead to concerns about therapy-induced immune damage reflected by the loss of protection of previous immunizations and the efficacy of (re-)vaccination. The severity of secondary immunodeficiency, however, is not clear and knowledge is based on a limited number of studies. We performed a systematic review on literature concerning vaccination data of children with ALL published since 1980. Eight studies fulfilled the inclusion criteria. Regarding antibody titers after treatment, the number of children who had preserved the defined protection level for antibodies differed widely, ranging from 17 to 98% for diphtheria, 27 to 82% for Bordetella pertussis, 20 to 98% for tetanus, 62 to 100% for poliomyelitis, 35 to 100% for Haemophilus influenzae type B (HiB), 29 to 92% for mumps, 29 to 60% for measles and 72 to 92% for rubella. Most patients however responded to revaccination, demonstrating immunological recovery. Although the designs and results of the included studies varied widely, it can be concluded that cytostatic therapy for ALL in children results in a temporarily reduction of specific antibody levels. Memory is preserved but revaccination may be warranted. This is the first systematic review and the best possible current approximation of chemotherapy-induced immune damage in children after ALL treatment.

  7. Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia : a population-matched analysis

    NARCIS (Netherlands)

    Dreger, P; Brand, R; Milligan, D; Corradini, P; Finke, J; Deliliers, GL; Martino, R; Russell, N; van Biezen, A; Michallet, M; Niederwieser, D

    To elucidate whether reduced-intensity conditioning (RIC) decreases treatment-related mortality (TRM) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL), we retrospectively compared 73 RIC cases from a recent EBMT survey with 82 patients from the EBMT

  8. Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT.

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    van Gorkom, Gwendolyn; van Gelder, Michel; Eikema, Dirk-Jan; Blok, Henric-Jan; van Lint, M T; Koc, Yener; Ciceri, Fabio; Beelen, Dietrich; Chevallier, Patrice; Selleslag, Dominik; Blaise, Didier; Foá, Roberto; Corradini, Paolo; Castagna, Luca; Moreno, Carol; Solano, Carlos; Müller, Lutz Peter; Tischer, Johanna; Hilgendorf, Inken; Hallek, Michael; Bittenbring, Jörg; Theobald, Matthias; Schetelig, Johannes; Kröger, Nicolaus

    2018-03-01

    Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.

  9. Ibrutinib as a bridge to transplant in high-risk chronic lymphocytic leukemia: A case report and review of the literature

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    Arcari Annalisa

    2017-01-01

    Full Text Available The treatment landscape of chronic lymphocytic leukemia (CLL has been challenged by the advent of novel classes of drugs, such as B-cell receptor (BCR-inhibitors and BCL-2 antagonists. In selected high-risk patients, the choice to start allogeneic hematopoietic stem cell transplantation (alloHCT or continue these agents is a matter of debate. Furthermore, published data about the impact on the feasibility of alloHCT and the optimal timing of administration are limited. Here we present a case of relapsed TP53 mutated CLL treated with ibrutinib as a bridge to alloHCT, discussing risks and benefits of different treatment options in a “real life” situation.

  10. The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

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    Mescher, Craig; Gilbertson, David; Randall, Nicole M; Tarchand, Gobind; Tomaska, Julie; Baumann Kreuziger, Lisa; Morrison, Vicki A

    2018-06-01

    Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

  11. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

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    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  12. A comparative immunohistochemical and immunophenotypical study on lymphocytes expression in patients affected by oral lichen planus.

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    Lorenzini, Guido; Viviano, Massimo; Chisci, Elettra; Chisci, Glauco; Picciotti, Maria

    2013-09-01

    Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa. A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group. The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102). We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. A comparative study of radioprotective effect of several antioxidants on human blood lymphocytes

    International Nuclear Information System (INIS)

    Wang Mingsuo; Zhu Gengbai; Gu Xuandi

    1992-01-01

    By means of improved fluorometric method with 2-thiobarbituric acid (TBA) as the fluorometric agent, radioprotective effects of four kinds of antioxidants on 60 Co γ-ray induced lipid peroxidation (LPO) level, i.e. Malondialdehyde (MDA) content changes in human blood lymphocytes were in human blood lymphocytes were compared by using relative protective efficiency (RPE) as an indicator. The LPO level in human lymphocytes which had been treated with an antioxidant at an concentration of 5 x 10 -3 g/L for 1 hr was measured 2 hr after exposure to 4 Gy of γ-rays, and the RPE values of antioxidants were calculated under these conditions: SOD, 38.23; VE, 23.75:VC, 19.32 and Se +4 , 18.27, thus the anticipation that the compounds, superoxide dismutase (SOD), 2-tocopherols (VE), ascorbic acid (VC) and Na 2 SeO 3 (Se +4 ) had radioprotective effects was confirmed. It was found that the radioprotective beneficial sequences of four kinds of antioxidants were arranged as SOD>VE>VC,Se +4 . The results show that radioprotective effects of exogenous antioxidants on radiation induced LPO damage are dependent not only on irradiation dosage, but also especially on property of antioxidants, drug concentration, pretreatment and monitoring time, etc. The mechanism of these antioxidants effecting as radioprotectants on human lymphocytes is discussed in connection with LPO damage and radioprotection

  14. Comparative analysis of chromosome aberrations induced in human lymphocytes in vitro by various types of ionizing radiations

    International Nuclear Information System (INIS)

    Todorov, S.L.

    1979-01-01

    Certain problems of comparative analyses of radiation-induced dicentrics in human lymphocytes following various types of ionizing radiations are considered as follows: 1. Equations best fitting for dose-response kinetics; 2. Use of dicentrics for analysing the RBE of various types of radiations; 3. The relationship between RBE and LET as seen by the analysis of dicentrics. (author)

  15. IgG4-related disease and lymphocyte-variant hypereosinophilic syndrome: A comparative case series.

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    Carruthers, Mollie N; Park, Sujin; Slack, Graham W; Dalal, Bakul I; Skinnider, Brian F; Schaeffer, David F; Dutz, Jan P; Law, Joanna K; Donnellan, Fergal; Marquez, Vladimir; Seidman, Michael; Wong, Patrick C; Mattman, Andre; Chen, Luke Y C

    2017-04-01

    To compare the clinical and laboratory features of IgG4-related disease (IgG4-RD) and lymphocyte-variant hypereosinophilic syndrome (L-HES), two rare diseases that often present with lymphadenopathy, gastrointestinal symptoms, eosinophilia, and elevated immunoglobulins/IgE. Comparative case series of 31 patients with IgG4-RD and 13 patients with L-HES. Peripheral blood eosinophilia was present in eight of 31 patients with IgG4-RD compared to 13 of 13 patients with L-HES (median eosinophils 0.4 vs 7.0 giga/L, P=.001) and 12 of 20 patients with IgG4-RD had increased serum IgE compared to eight of 13 patients with L-HES, P=.930. Twenty-seven of 30 patients with IgG4-RD had elevated serum IgG4 compared to five of 12 patients with L-HES (median IgG4 9.6 g/L vs 0.80 g/L, P=.002). Flow cytometry demonstrated an aberrant T-cell phenotype in 7 of 23 patients with IgG4-RD and 13 of 13 patients with L-HES (PIgG4-RD vs 10 of 13 patients with L-HES (P=.143). Patients in both groups received corticosteroids as first-line therapy. For refractory disease in IgG4-RD, rituximab was the most common steroid-sparing agent, whereas in L-HES, it was pegylated interferon-α-2a. The overlapping features of these two diseases with divergent treatment options demonstrate the importance of familiarity with both entities to optimize diagnosis and treatment. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

  16. A comparative immunohistochemical study of aplastic thymuses for lymphocytic, epithelial, proliferative and apoptotic indices

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    Mahjoub F.

    2008-03-01

    Full Text Available Background: Immune deficiency is one of the major causes of morbidity and mortality in the modern world. Primary immunodeficiency comprises a wide range of disorders that mainly manifest in early childhood as devastating infections with opportunistic organisms. Thymic aplasia is found on autopsy of some patients afflicted with immune deficiency disorders, such as DiGeorge syndrome and severe combined immunodeficiency (SCID. After a thorough search of the literature, we found little information on the cellular characteristics of these thymuses. Our study aims to elucidate role of apoptosis in the pathogenesis of thymic aplasia and compare various lymphocytic and epithelial markers in normal and aplastic thymuses. Methods: We selected 12 subjects who died of severe infections with aplastic thymus found on autopsy, and 11 control subjects who died of unrelated causes, such as congenital heart disease. The presence of several markers, including Bcl2, P53, lymphocytic markers, and CD68, was examined using immunohistochemical methods on paraffin-embedded thymus sections. Positively-stained cells were counted per 1000 cells and the results stated as percentage of positive cells.                        Results: The mean age of the control group was between 7 days to 18 months (mean: 4.5 months. Parental consanguinity was present in 45.5% and 9.1% of the control and case groups, respectively; however, this was not statistically significant. We found significantly lower expression of Bcl2 in the case group (p value: 0.038. Furthermore, expression of CD68 was significantly higher in the case group. Epithelial markers were significantly higher in case subjects, although CD8 expression was higher in the control group. The presence of other markers was not significantly different between the two groups.Conclusions: Increase in apoptosis has a role in aplastic thymuses and prevention of apoptosis may halt this process. Also high CD68

  17. Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

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    Santos, Rodrigo Ribeiro; Torres, Karen C; Lima, Giselle S; Fiamoncini, Carolina M; Mapa, Filipe C; Pereira, Patricia A; Rezende, Vitor B; Martins, Luiza C; Bicalho, Maria A; Moraes, Edgar N; Reis, Helton J; Teixeira, Antonio L; Romano-Silva, Marco A

    2014-01-03

    Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia. © 2013 Elsevier Inc. All rights reserved.

  18. Microprocessor-controlled vs. "dump-freezing" platelet and lymphocyte cryopreservation: A quantitative and qualitative comparative study

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    Balint Bela

    2006-01-01

    Full Text Available Background/Aim. Thermodynamical and cryobiological parameters responsible for cell damages during cryopreservation (cryoinjuries have not yet been completely explained. Thus, freezing procedures should be revised, exactly optimized to obtain an enhanced structural and functional recovery of frozen- thawed cells. The aim of this study was to compare microprocessor- controlled (controlled-rate with the compensation of the released fusion heat and “dump-freezing” (uncontrolled- rate of the platelet and lymphocyte cryopreservation efficacy. Methods. Platelet quantitative recovery (post-thaw vs. unfrozen cell count, viability (using hypotonic shock response - HSR, morphological score (PMS, ultrastructural (electron microscopy properties and expression of different surface antigens were investigated. In lymphocyte setting, cell recovery and viability (using trypan blue exclusion test as well as functionality (by plant mitogens were determined. Controlled- rate freezing and uncontrolled-rate cryopreservation were combined with 6% (platelets and 10% (lymphocytes dimethyl sulfoxide (DMSO. Results. Platelet recovery and functionality were superior in the controlled-rate system. The majority of surface antigen expression was reduced in both freezing groups vs. unfrozen cells, but GP140/CD62p was significantly higher in controlled-rate vs. uncontrolled-rate setting. Controlled- rate freezing resulted with better lymphocyte recovery and viability (trypan blue-negative cell percentage. In mitogen-induced lymphocyte proliferative response no significant intergroup difference (controlled-rate vs. uncontrolled-rate were found. Conclusion. The data obtained in this study showned the dependence of cell response on the cryopreservation type. Controlled-rate freezing provided a superior platelet quantitative and functional recovery. Lymphocyte recovery and viability were better in the controlled-rate group, although only a minor intergroup difference for cell

  19. Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

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    Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

    2018-03-27

    The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

  20. A comparative analysis of coronary adventitial T-lymphocytes - an autopsy study

    International Nuclear Information System (INIS)

    Zubair, A.; Mubarik, A.; Jamal, S.; Naz, S.

    2010-01-01

    Background: Recent clinical and histopathologic data suggests that inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. The intima has received much attention as a site of inflammation, while the adventitia has remained relatively unexplored. The aim of the present study was to investigate the frequency of inflammatory activity in the cap and shoulder region of un ruptured, atherosclerotic lesions in coronary arteries and to correlate these findings with distribution of inflammatory cells in adventitia. Methods: The study was carried out in Histopathology Department, Army Medical College, Rawalpindi and National University of Sciences and Technology (NUST), from August 2008 to July 2009. Sixty-seven autopsy cases performed at Military Hospital Rawalpindi, Pakistan were selected. The cases were divided into study group and control group. Case group (n=35) included those where cause of death was ischemic heart disease. Those coronary arteries were taken as control (n=32) where atherosclerotic changes were found by chance (death without history of ischemic heart disease). Plaques in each group were assessed by light microscopy and by immunohistochemistry. Results: The ages of the deceased ranged from 38 to 49 years. Within study group, adventitial lymphocytes exhibited strong correlation with erosion, thrombus formation in culprit plaque (p=0.001). No correlation was found between adventitial T-lymphocytes and erosion of plaque (p=0.700) in control group. In 72% of culprit plaques moderate staining for T-lymphocytes was observed in adventitia as well as intima. In control group, most of the cases contained scattered cells. Few cases of stable plaques revealed lymphocytes as clusters, both in adventitia and in intima. Conclusion: Adventitial inflammation may play a pivotal role for atherosclerotic lesion histology and atheroma instability. With the help of these autopsy findings, we hope to be able to reduce the

  1. Hyper-CVAD Compared With BFM-like Chemotherapy for the Treatment of Adult Acute Lymphoblastic Leukemia. A Retrospective Single-Center Analysis.

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    El-Cheikh, Jean; El Dika, Imane; Massoud, Radwan; Charafeddine, Maya; Mahfouz, Rami; Kharfan-Dabaja, Mohamed A; Bazarbachi, Ali

    2017-03-01

    Several induction regimens have been developed for treatment of adult patients with acute lymphoblastic leukemia (ALL). However, only a few prospective randomized trials have directly compared these regimens. In this report, we retrospectively evaluated the outcome of 62 adult ALL patients treated with either hyper-CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 38) or a BFM (Berlin-Frankfurt-Munster)-like regimen (n = 24) between November 2000 and January 2016 at the American university of Beirut Medical Center in Lebanon. The feasibility of allogeneic stem cell transplantation (allo-SCT) for those patients was also evaluated. The median follow-up time was 29 (range, 1-129) months. Fifteen (39%) and 10 (42%) patients underwent allo-SCT in the hyper-CVAD and BFM-like group, respectively. At the time of the last follow-up, 28 patients (74%) were in complete remission in the hyper-CVAD group versus 18 patients (75%) in the BFM-like group. Of those, 20 patients (53%) versus 11 patients (46%) were minimal residual disease-negative at the last follow-up, respectively. The 3-year overall survival rate (71.9% vs. 76.9%; P = .808) and 3-year disease-free survival (54.7% vs. 76.4%; P = .435) were similar in hyper-CVAD group compared with the BFM-like group, respectively. Both chemotherapies were relatively well tolerated. Overall, despite the older age and a greater number of patients with high-risk category (including Philadelphia chromosome-positive) in the hyper-CVAD group, this did not translate into a difference in survival outcome between the 2 groups. The hyper-CVAD regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Comparative analysis of succinate dehydrogenase activity in mammalian peripheral blood lymphocytes and radiomodifying action of gas hypoxis mixtures

    International Nuclear Information System (INIS)

    Gajdamakin, A.N.; Abramov, M.M.

    1987-01-01

    Radiprotective efficiency of gas hypoxic mixtures (GHM) containing 5-12% of oxygen and the rate of the reaction of succinate dehydrogenase (V SDG ) activity in peripheral blood lymphocytes upon breathing GHM were comparatively studied in rats and dogs. V SDG was 4393.5 (%O 2 ) -2,58 and 130.76 (%O 2 ) -1.42 in dogs and rats respectively. Taking into account that DMF in rats is a function of oxygen concentration in the mixture one can obtain a formula for determining a dose modifying factors (DMF) as a function of the rate of SDG activity reaction

  3. Quantitative analysis of the chromatin of lymphocytes: an assay on comparative structuralism.

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    Meyer, F

    1980-01-01

    With 26 letters we can form all the words we use, and with a few words it is possible to form an infinite number of different meaningful sentences. In our case, the letters will be a few simple neighborhood image transformations and area measurements. The paper shows how, by iterating these transformations, it is possible to obtain a good quantitative description of the nuclear structure of Feulgen-stained lymphocytes (CLL and normal). The fact that we restricted ourselves to a small number of image transformations made it possible to construct an image analysis system (TAS) able to do these transformations very quickly. We will see, successively, how to segment the nucleus itself, the chromatin, and the interchromatinic channels, how openings and closings lead to size and spatial distribution curves, and how skeletons may be used for measuring the lengths of interchromatinic channels.

  4. Definite vs adjuvant radiotherapy. Comparative effects on lymphocyte subpopulations in patients with head and neck squamous carcinoma

    International Nuclear Information System (INIS)

    Wolf, G.T.; Amendola, B.E.; Diaz, R.; Lovett, E.J. III; Hammerschmidt, R.M.; Peterson, K.A.

    1985-01-01

    The recent association of alterations in T-lymphocyte subpopulations and impaired cellular immunity prompted an investigation of the effects of radiotherapy (RT) on serial levels of lymphocyte subsets in 30 patients with head and neck squamous carcinoma. Percentage and absolute levels of T3, T4, T6, T8, T10, T11, and Leu 7 cells were measured before, during, and after RT at monthly intervals for six months and compared with levels in 40 normal subjects. Sixteen patients received curative and 14 postoperative adjuvant RT. Before treatment, mean subset levels were similar among the patient and normal groups except for elevated Leu 7 (natural killer) cells in patients with stage I and II disease. There were profound decreases in absolute levels of each subpopulation during and after RT. The percentage of T4 (helper/inducer) cells decreased, whereas that of T8 (cytotoxic/suppressor) and Leu 7 cells tended to increase. Compared with normal values, the mean T4/T8 ratio decreased significantly by six months after RT, when absolute levels of the subsets had rebounded to pretreatment levels in the definitive RT group but remained profoundly decreased in the adjuvant group. The differing recovery patterns suggest that factors other than RT may contribute to persistent immunosuppression following RT

  5. Determination of CD4+ and CD8+ lymphocytes with the cytosphere assay: a comparative study with flow cytometry and the immunoalkaline phosphatase method

    DEFF Research Database (Denmark)

    Gernow, A; Lisse, I M; Böttiger, B

    1995-01-01

    number of CD4+ lymphocytes determined by CA showed a good correlation with results obtained by FC (correlation coefficients were 0.92 and 0.74 in Denmark and The Ivory Coast, respectively) and IA (correlation coefficients were 0.94 and 0.66 in Denmark and The Ivory Coast, respectively). However, for HIV......The proportion and absolute numbers of CD4+ and CD8+ lymphocytes in peripheral blood were determined using a new manual method, the cytosphere assay (CA). This method uses small latex beads coated with monoclonal antibodies directed against the CD4 and CD8 receptors, respectively. The CA...... was compared with two other methods for determination of T lymphocyte subsets, flow cytometry (FC) and the immunoalkaline phosphatase (IA) method, by testing HIV-seropositive and HIV-seronegative samples from Denmark (44) and Ivory Coast (79). For HIV-seropositive samples, both the proportion and the absolute...

  6. Preoperative lymphocyte-to-monocyte ratio represents a superior predictor compared with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for colorectal liver-only metastases survival

    Directory of Open Access Journals (Sweden)

    Peng JH

    2017-07-01

    Full Text Available Jianhong Peng,1,* Hui Li,2,* Qingjian Ou,1,* Junzhong Lin,1 Xiaojun Wu,1 Zhenhai Lu,1 Yunfei Yuan,1 Desen Wan,1 Yujing Fang,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR in patients with colorectal liver-only metastases (CLOM undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS and overall survival (OS related to the LMR, NLR, and PLR were analyzed using both Kaplan–Meier and multivariate Cox regression methods. Elevated LMR (≥2.82 and lower NLR (<4.63 were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17. Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32–0.844; P=0.008 and OS (hazard ratio, 0.426; 95% CI, 0.254–0.716; P=0.001. In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non

  7. Comparative studies on Fc receptors for IgG on resting and activated T lymphocytes

    International Nuclear Information System (INIS)

    Hueckel, C.; Jensen, H.L.; Rychly, J.; Sandor, M.; Erdei, A.; Gergely, J.

    1986-01-01

    Fc-receptors for IgG (FcγR) on resting (i.e. freshly prepared) and mitogen (Con A) or alloantigen-activated mouse spleen T cells were compared using binding of different markers such as 125 I-labelled immune complexes, 125 I-labelled anti FcγR monoclonal antibody, FITC-labelled aggr. IgG and sheep erythrocytes covered with specific antibody (EA rosetting). C3b receptors were detected by rosetting with sheep erythrocytes covered with antibody and complement (EAC rosetting). The electrophoretic mobility of the cells without or after binding of aggr. IgG was also tested. Differences between resting and activated T cells were found: (1) After activation of T cells by mitogen or alloantigen, a proportion of FcγR-positive cells increased two to four times. (2) FcγR number per FcγR-positive cell seemed to be higher on activated then on resting cells. (3) FcγR-positive resting cells did not shed their FcγR upon incubation at 4 0 C followed by incubation at 37 0 C, but FcγR-positive activated cells shed a remarkable proportion of their FcγR on the same conditions. (4) Binding of aggr. IgG caused a decrease of electrophoretic mobility of activated but not resting cells. (5) FcγR-positive resting cells were also C3b receptor-positive, whereas FcγR-positive activated cells had no detectable C3b receptors. (author)

  8. Comparative studies on radiation induced chromosome aberrations in the peripheral blood lymphocytes in primates

    International Nuclear Information System (INIS)

    Tobari, Izuo; Hirai, Momoki; Takahashi, Eiichi; Nakai, Sayaka; Utugi, Toyoko

    1978-01-01

    In order to obtain the information regarding interspesific extrapolation of the production of chromosome aberrations, we have examined species difference in the yields of dicentrics induced by the acute or chronic irradiations of gamma-rays. After acute irradiation, there were no significant differences in the yields among four primate species, man, crab-eating monkey, squirrel monkey and slow loris, in spite of the difference in chromosome arm number. On the other hand, after chronic irradiation, a significant difference in the yields was observed between man and crab-eating monkey. Comparing the α and β values estimated by fitting the observed yields with linear-quadratic equation, the value of β was clearly different between acute and chronic irradiations for both man and monkey. Furthermore, at low dose rate the value of β for monkey was almost negligible, while it was somewhat measurable one for man. To clarify the mechanism(s) involved in the species difference in the yields of dicentrics induced by chronic irradiation, post-irradiation incubation experiment was carried out. The considerable reductions of both the yields of dicentrics and mitotic indices during post-irradiation incubation periods under unstimulated conditions may probably indicate that cells with dicentrics are partly eliminated in the course of chronic irradiation for both man and monkey. However, the elimination mechanism is not sufficient to explain the reduction of dicentric yields after chronic irradiation. Consequently, Go repair mechanism(s) may presumably be responsible for the dose-rate effects, and the different amount of reduction of dicentric yields between man and monkey may reflect the different ability of Go repair between them. (author)

  9. Comparative analysis of chromosome aberrations in human lymphocytes induced 'in vitro' by various types of ionizing radiation

    International Nuclear Information System (INIS)

    Todorov, S.

    1975-01-01

    A quantitative analysis on various types of chromosome aberrations in human peripheral blood lymphocytes after in vitro whole blood irradiation with 180 kV X-rays, gamma rays from cobalt 60, 50 MeV protons and scission neutrons is carried out. The following aberrations are scored: breaks, total number of aberrations, aberrant cells, chromosome fragments, dicentrics and interstitial deletions. The experimental data obtained are statistically processed applying the method of the least squares and employing four mathematical models: Y = cD 2 , Y = cD, Y = a + bD and Y = a + bD + cD 2 . Statistical analysis showed that after treatment with low LET (linear energy transfer) radiations the most suitable for the description of the kinetic of the two break aberrations, total number of aberrations and breaks in relation to dose is the polynomial second degree model, whereas for one break aberrations and aberrant cells - the linear model. The linear model is equally appropriate for one or two breaks aberrations when it is a matter of high LET radiations. Using the linear component of the polynominal second degree equation a comparative characteristic of the RBE (relative biological effectiveness) for the various radiations types is made. The following mean values for RBE are obtained: 0,86 +- 0,44 for gamma radiation from cobalt 60, 0,98 +- 0,06 for 50 MeV protons and 2,38 +- 0,11 for scission neutrons. (A.B.)

  10. Morphologic identification of atypical chronic lymphocytic leukemia by digital microscopy.

    Science.gov (United States)

    Marionneaux, S; Maslak, P; Keohane, E M

    2014-08-01

    Atypical chronic lymphocytic leukemia (aCLL) is a morphologic variant found in approximately 25% of patients with chronic lymphocytic leukemia (CLL). Although aCLL has a more aggressive course compared to typical CLL (tCLL), it is not usually reported. This retrospective study used digital microscopy to morphologically classify CLL patients as aCLL or tCLL, and determined the prevalence of prognostic markers in each group. CellaVision AB (Lund, Sweden) was used to evaluate lymphocyte morphology on archived blood films of 97 CLL patients, and results of their prognostic marker analysis at diagnosis were obtained. The unpaired t-test, Chi-square, or Fisher's Exact test were used for statistical analysis. 27% of CLL cases were morphologically classified as aCLL. The aCLL group had a higher prevalence of trisomy 12, unmutated IgVH, and CD38 expression (markers associated with poor prognosis), and a lower prevalence of 13q14 deletions compared to tCLL; this was statistically significant. Using digital imaging to identify aCLL is feasible, economical, and may provide clinically relevant prognostic information at diagnosis and during periodic monitoring. Further study of a larger number of patients is needed to assess the clinical utility of reporting aCLL morphology. © 2013 John Wiley & Sons Ltd.

  11. Comparative effects of inhaled relatively insoluble forms of 90Y, 144Ce, and 90Sr on canine peripheral lymphocyte function

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Jones, R.K.; Snipes, M.B.; Lustgarten, C.S.

    1976-01-01

    Dogs that have inhaled relatively insoluble forms of either alpha- or beta-emitting radionuclides manifest a peripheral lymphopenia, the development and course of which depends on both total dose and dose rate. The remaining peripheral lymphocytes in dogs exposed to longer lived beta-emitting radionuclides showed a depressed function as measured by the ability to respond to plant mitogens in vitro. This experiment was designed to evaluate the effect of dose rate on peripheral lymphocyte function by exposing dogs to aerosols of radionuclides with varied effective half-lives in the lung: 90 Y (2.6 days), 144 Ce (170 days), and 90 Sr (650 days). Three groups of four adult beagle dogs each were exposed by inhalation to 90 Y, 144 Ce, or 90 Sr in fused-clay particles. Two controls were matched with each group. Initial lung burdens and initial dose rates to the lung were 520 to 610 μCi/kg of body weight and 2200 to 2600 rads/day in the 90 Y group, 33 to 60 μCi/kg and 200 to 350 rads/day in the 144 Ce group, and 25 to 32 μCi/kg and 130 to 170 rads/day in the 90 Sr group. Hematologic parameters and lymphocyte function as measured by the ability of lymphocytes to respond to plant mitogen stimulation were evaluated on a weekly or biweekly basis for 8 weeks after exposure and on a monthly basis thereafter. The 90 Y-exposed dogs showed a marked lymphopenia within 1 week with a return to control levels by 20 weeks after exposure. The remaining peripheral lymphocytes, however, showed no functional changes in these dogs. Animals exposed to 144 Ce or 90 Sr developed a progressive and persisent lymphopenia and showed functional depression of the remaining lymphocytes as well. The relationships among dose pattern, lymphopenia, and lymphocyte-function depression are discussed

  12. Comparative Microarray Analysis of Intestinal Lymphocytes following Eimeria acervulina, E. maxima, or E. tenella Infection in the Chicken

    Science.gov (United States)

    Kim, Duk Kyung; Lillehoj, Hyun; Min, Wongi; Kim, Chul Hong; Park, Myeong Seon; Hong, Yeong Ho; Lillehoj, Erik P.

    2011-01-01

    Relative expression levels of immune- and non-immune-related mRNAs in chicken intestinal intraepithelial lymphocytes experimentally infected with Eimeria acervulina, E. maxima, or E. tenella were measured using a 10K cDNA microarray. Based on a cutoff of >2.0-fold differential expression compared with uninfected controls, relatively equal numbers of transcripts were altered by the three Eimeria infections at 1, 2, and 3 days post-primary infection. By contrast, E. tenella elicited the greatest number of altered transcripts at 4, 5, and 6 days post-primary infection, and at all time points following secondary infection. When analyzed on the basis of up- or down-regulated transcript levels over the entire 6 day infection periods, approximately equal numbers of up-regulated transcripts were detected following E. tenella primary (1,469) and secondary (1,459) infections, with a greater number of down-regulated mRNAs following secondary (1,063) vs. primary (890) infection. On the contrary, relatively few mRNA were modulated following primary infection with E. acervulina (35 up, 160 down) or E. maxima (65 up, 148 down) compared with secondary infection (E. acervulina, 1,142 up, 1,289 down; E. maxima, 368 up, 1,349 down). With all three coccidia, biological pathway analysis identified the altered transcripts as belonging to the categories of “Disease and Disorder” and “Physiological System Development and Function”. Sixteen intracellular signaling pathways were identified from the differentially expressed transcripts following Eimeria infection, with the greatest significance observed following E. acervulina infection. Taken together, this new information will expand our understanding of host-pathogen interactions in avian coccidiosis and contribute to the development of novel disease control strategies. PMID:22140460

  13. Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia.

    Science.gov (United States)

    Biancotto, Angélique; Dagur, Pradeep K; Fuchs, John C; Wiestner, Adrian; Bagwell, C Bruce; McCoy, J Philip

    2012-02-01

    Increased numbers of T regulatory (T(reg)) cells are found in B-chronic lymphocytic leukemia, but the nature and function of these T(regs) remains unclear. Detailed characterization of the T(regs) in chronic lymphocytic leukemia has not been performed and the degree of heterogeneity of among these cells has not been studied to date. Using 15-color flow cytometry we show that T(reg) cells, defined using CD4, CD25, and forkhead box P3 (FOXP3), can be divided into multiple complex subsets based on markers used for naïve, memory, and effector delineation as well as markers of T(reg) activation. Furthermore FOXP3(+) cells can be identified among CD4(+)CD25(-) as well as CD8(+)CD4(-) populations in increased proportions in patients with chronic lymphocytic leukemia compared with healthy donors. Significantly different frequencies of naïve and effector T(regs) populations are found in healthy donor controls compared with donors with chronic lymphocytic leukemia. A population of CCR7(+)CD39(+) T(regs) was significantly associated with chronic lymphocytic leukemia. This population demonstrated slightly reduced suppressive activity compared with total T(regs) or T(regs) of healthy donors. These data suggest that FOXP3-expressing cells, particularly in patients with chronic lymphocytic leukemia are much more complex for T(reg) sub-populations and transitions than previously reported. These findings demonstrate the complexity of regulation of T-cell responses in chronic lymphocytic leukemia and illustrate the use of high-dimensional analysis of cellular phenotypes in facilitating understanding of the intricacies of cellular immune responses and their dysregulation in cancer.

  14. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

    Science.gov (United States)

    Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

    2016-02-01

    Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

  15. A comparative study of radiation induced DNA damage and repair in buccal cells and lymphocytes assessed by single cell gel electrophoresis (comet) assay

    International Nuclear Information System (INIS)

    Dhillon, V.S.; Fenech, M.

    2003-01-01

    Full text: During the past few years, there has been increasing interest in epithelial cells from buccal mucosa for genotoxicity evaluation of different chemical and/or physical agents. In the present study we used the buccal and sublingual epithelial cells to detect both inter- and intra-individual variation in radiation induced DNA damage and repair. For this purpose we used the single cell gel electrophoresis assay which over the years has gained wide spread acceptance as a simple, sensitive and reliable assay to measure genotoxicity related effects as well as kinetics of DNA repair. Buccal and sublingual epithelial cells from six individuals (3 male and 3 females; 35-45 years old) were collected. Cells were then irradiated for 0, 2 and 4 Gy doses using 137 Cs-source (5.58 Gy min-1). After irradiation the cells were either placed immediately on ice or incubated at 37 deg C for 2 1/2 hour to allow cellular repair. We also studied G0 and G1 lymphocytes from the same individuals to compare the radiation-induced DNA damage and repair potential with the two types of buccal cells. Baseline DNA damage rate was significantly greater (p < 0.001) in buccal (28.18%) and sublingual epithelial cells (30.66) as compared to G0 (22.02%) and G1 (21.46%) lymphocytes. Radiation-induced DNA damage in buccal (19.34%, 2Gy; 21.41%, 4 Gy) and sublingual epithelial cells (18.11% and 20.60%) was very similar and significantly lower than that observed in lymphocytes (29.76%, 56.77% for G0 and 32.66%, 59.32% for G1). The extent of DNA repair in buccal and sublingual epithelial cells was significantly lower than that observed in lymphocytes. The results for buccal and sublingual epithelial cells were highly correlated with each other (r 0.9541) as were those of G0 and G1 lymphocytes (r 0.9868). The results suggest a much reduced capacity for cellular repair in buccal and sublingual epithelial cells

  16. Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Siviero-Miachon, Adriana Aparecida; Spinola-Castro, Angela Maria; Lee, Maria Lúcia de Martino; Andreoni, Solange; Geloneze, Bruno; Lederman, Henrique; Guerra-Junior, Gil

    2013-01-01

    Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process

  17. Peripheral blood B lymphocytes derived from patients with idiopathic pulmonary arterial hypertension express a different RNA pattern compared with healthy controls: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Huber Lars C

    2008-02-01

    Full Text Available Abstract Background Idiopathic pulmonary arterial hypertension (IPAH is a progressive and still incurable disease. Research of IPAH-pathogenesis is complicated by the lack of a direct access to the involved tissue, the human pulmonary vasculature. Various auto-antibodies have been described in the blood of patients with IPAH. The purpose of the present work was therefore to comparatively analyze peripheral blood B lymphocyte RNA expression characteristics in IPAH and healthy controls. Methods Patients were diagnosed having IPAH according to WHO (mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary occlusion pressure ≤ 15 mmHg, absence of another explaining disease. Peripheral blood B-lymphocytes of patients and controls were immediately separated by density gradient centrifugation and magnetic beads for CD19. RNA was thereafter extracted and analyzed by the use of a high sensitivity gene chip (Affymetrix HG-U133-Plus2 able to analyze 47000 transcripts and variants of human genes. The array data were analyzed by two different softwares, and up-and down-regulations were defined as at least 1.3 fold with standard deviations smaller than fold-changes. Results Highly purified B-cells of 5 patients with IPAH (mean pulmonary artery pressure 51 ± 13 mmHg and 5 controls were analyzed. Using the two different analyzing methods we found 225 respectively 128 transcripts which were up-regulated (1.3–30.7 fold in IPAH compared with healthy controls. Combining both methods, there were 33 overlapping up-regulated transcripts and no down-regulated B-cell transcripts. Conclusion Patients with IPAH have a distinct RNA expression profile of their peripheral blood B-lymphocytes compared to healthy controls with some clearly up-regulated genes. Our finding suggests that in IPAH patients B cells are activated.

  18. Proquazone: a treatment for lymphocytic infiltration of the skin. Comparative study with 2 other nonsteroid anti-inflammatory drugs.

    Science.gov (United States)

    Johansson, E A

    1987-01-01

    15 patients with lymphocytic infiltration of the skin (LIS) were treated with the nonsteroid anti-inflammatory (NSAI) drug proquazone [1-isopropyl-4-phenyl-7-methyl-2(IH)]. In contrast to other NSAI drugs proquazone is a nonacidic compound which is known to be a potent prostaglandin synthesis inhibitor. Of the 15 patients 8 were healed completely with proquazone; in half of these patients lesions recurred but healed with reintroduction of the drug. Two patients remained symptom-free with a small maintenance dose. Two patients showed a partial remission. The treatment was discontinued in 3 patients, in 2 of them because of side effects and in 1 because of lack of response. Two other NSAI drugs, both known to be potent prostaglandin synthesis inhibitors, namely indomethacin and ibuprofen, were tried, however without effect. The present study indicates that proquazone should be considered in the treatment of LIS.

  19. β-cell specific T-lymphocyte response has a distinct inflammatory phenotype in children with Type 1 diabetes compared with adults.

    Science.gov (United States)

    Arif, S; Gibson, V B; Nguyen, V; Bingley, P J; Todd, J A; Guy, C; Dunger, D B; Dayan, C M; Powrie, J; Lorenc, A; Peakman, M

    2017-03-01

    To examine the hypothesis that the quality, magnitude and breadth of helper T-lymphocyte responses to β cells differ in Type 1 diabetes according to diagnosis in childhood or adulthood. We studied helper T-lymphocyte reactivity against β-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings. Interferon-γ responses were significantly more frequent in children with Type 1 diabetes compared with adults (85 vs 61%; P = 0.04). Insulin and proinsulin peptides were preferentially targeted in children (P = 0.0001 and P = 0.04, respectively) and the breadth of the interferon-γ response was also greater, with 70% of children having an interferon-γ response to three or more peptides compared with 14% of adults (P children and adults in terms of frequency, breadth and magnitude, with the exception of responses to glutamic acid decarboxylase 65, which were significantly less frequent in adults. At diagnosis of Type 1 diabetes, pro-inflammatory autoreactivity is significantly more prevalent, focuses on a wider range of targets, and is more focused on insulin/proinsulin in children than adults. We interpret this as indicating a more aggressive immunological response in the younger age group that is especially characterized by loss of tolerance to proinsulin. These findings highlight the existence of age-related heterogeneity in Type 1 diabetes pathogenesis that could have relevance to the development of immune-based therapies. © 2016 Diabetes UK.

  20. Comparative study of dose-response curve for chromosome aberrations induced in human lymphocytes by {sup 60}Co and X-Rays

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Mendonça, Julyanne C.G.; Andrade, Aida M.G.; Silva, Laís M.; Hwang, Suy; Melo, Ana M.M.A.; Santos, Neide; Lima, Fabiana F., E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2017-11-01

    Biodosimetry represents a biological marker to the estimation of health risks after accidental overexposure to ionizing radiation. Chromosomal dicentric in peripheral blood lymphocytes have been the most reliable biomarker of exposure to IR during the last several decades. This technique could be used to support physical dosimetry or when it is impossible to achieve it. A reliable measurement of the absorbed dose is critical for medical decision, including the assessment of long-term health consequences. The aim of this research is to compare dose-response curves for dicentric aberration induced in human lymphocytes by {sup 60}Co and X-Rays. For both quality of radiation, the samples were exposed to at least eight different absorbed doses. The X-rays with dose rate of 0,275 Gy/min at Laboratory of Metrology (CRCN/NE - PE - Brazil) and the second one was exposed to cobalt source with dose rate of 0.055 Gy/min ({sup 60}Co Gammacell 220) located at Department of Nuclear Energy (UFPE-DEN-BRASIL). Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. The frequencies of dicentrics were counted in more than 18.000 metaphases for this comparison. After that, all frequencies and distributions of dicentrics were tested to analyze their conformity with Poisson distribution and then each quality of radiation were used for build the calibration curves using Dose Estimate program. These results showed that both curves followed the Poisson distribution and coefficients of each one are: YX-rays = 0,0013 (± 0,0006) + 0,0271 (± 0,0086)⁎D + 0,0556(±0,0050))⁎D{sup 2} and Y{sub Co-60} = 0,0014 (± 0,0010) + 0,0081 (± 0,0073))⁎D + 0,0451 (± 0,0046))⁎D{sup 2} (Y = frequency of dicentrics and D = absorbed dose). It was expected that there was no significant difference between this two types of radiation because both were low LET. We believed that dose rate have been a principal factor to produce this

  1. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

    Science.gov (United States)

    Loi, Sherene; Sirtaine, Nicolas; Piette, Fanny; Salgado, Roberto; Viale, Giuseppe; Van Eenoo, Françoise; Rouas, Ghizlane; Francis, Prudence; Crown, John P A; Hitre, Erika; de Azambuja, Evandro; Quinaux, Emmanuel; Di Leo, Angelo; Michiels, Stefan; Piccart, Martine J; Sotiriou, Christos

    2013-03-01

    Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes. We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. There was no significant prognostic association in the global nor estrogen receptor (ER) -positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor

  2. Cost-Effectiveness of Ibrutinib Compared With Obinutuzumab With Chlorambucil in Untreated Chronic Lymphocytic Leukemia Patients With Comorbidities in the United Kingdom.

    Science.gov (United States)

    Sinha, Richa; Redekop, William Ken

    2018-02-01

    Ibrutinib shows superiority over obinutuzumab with chlorambucil (G-Clb) in untreated patients with chronic lymphocytic leukemia with comorbidities who cannot tolerate fludarabine-based therapy. However, ibrutinib is relatively more expensive than G-Clb. In this study we evaluated the cost-effectiveness of ibrutinib compared with G-Clb from the United Kingdom (UK) health care perspective. A 3-state semi-Markov model was parameterized to estimate the lifetime costs and benefits associated with ibrutinib compared with G-Clb as first-line treatment. Idelalisib with rituximab was considered as second-line treatment. Unit costs were derived from standard sources, (dis)utilities from UK elicitation studies, progression-free survival, progression, and death from clinical trials, and postprogression survival and background mortality from published sources. Additional analyses included threshold analyses with ibrutinib and idelalisib at various discount rates, and scenario analysis with ibrutinib as second-line treatment after G-Clb. An average gain of 1.49 quality-adjusted life-years (QALYs) was estimated for ibrutinib compared with G-Clb at an average additional cost of £112,835 per patient. To be cost-effective as per the UK thresholds, ibrutinib needs to be discounted at 30%, 40%, and 50% if idelalisib is discounted at 0%, 25%, and 50% respectively. The incremental cost-effectiveness ratio was £75,648 and £-143,279 per QALY gained for the base-case and scenario analyses, respectively. Sensitivity analyses showed the robustness of the results. As per base-case analyses, an adequate discount on ibrutinib is required to make it cost-effective as per the UK thresholds. The scenario analysis substantiates ibrutinib's cost-savings for the UK National Health Services and advocates patient's access to ibrutinib in the UK. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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

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

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    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.

  5. Infectious complications in chronic lymphocytic leukemia- a retrospective analysis: single institution experience.

    Science.gov (United States)

    Demitrovicova, L; Mikuskova, E; Oravcova, I; Cingelova, S; Drgona, L; Mladosievicova, B

    2017-01-01

    The aim of this study was to evaluate the incidence of a variety of infectious complications in patients with CLL regarding the duration of CLL and the type of treatment. We present the retrospective analysis of patients with CLL treated at our institution in years 2004-2016. We collected data about the type of infection, pathogenes, treatment and severity of infections surpassed in connection with administration treatment. In the study one hundred and ten patients were evaluated. The average age of patients was 61.7 years (range 34.5-91.9 years). Fludarabine was the most widely used regimen, followed by bendamustine and alemtuzumab. We recorded 393 episodes of infections, of which 114 (29%) were severe and life threatening of degree 3-5, and 279 (71%) of degree 2. The most common infections were the upper respiratory tract infections together with sinusitis (45.03%), pneumonia (26.20%), CMV reactivation occured in 8.14%, infections of the skin was in 7.6 %. Most infections have occurred with the administration of monoclonal antibody alemtuzumab, these patients were at significantly higher risk of infection [RR 2.59 (1.30 to 5.17)] than patients receiving obinutuzumab [RR 0.63 (0.48 to 0.82)] (p = 0.0001). On the contrary, the safety profile of BCR signaling pathway inhibitors was very acceptable [RR 1.17 (0.70 - 1.96)]. The number of infections have decreased during the first 12 months of treatment with ibrutinib. In the study group we recorded 19 deaths, 8 (7.27%) of them were of infectious etiology. The risk of infectious complications is lifelong in patients with CLL, it can be minimized by early detection and aggressive management. Novel targeted agents used in therapy of CLL have a good safety profile, even the risk of infection is decreased during administration.

  6. The effect of gamma ray on total leukocytes, lymphocytes and neutrophils on blood samples of smokers compared to non-smoker donors

    Directory of Open Access Journals (Sweden)

    Baydaa Taher Sih

    2017-01-01

    Conclusions: By increases the doses of γ-ray, the declining in the values of WBCs, lymphocytes, and neutrophils in the smokers blood is greater than of nonsmokers and this confirms that these cells are more fragile, weak, and less tolerant to external stimuli.

  7. 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 ...

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Comparative study of lymphocytes from individuals that were vaccinated and unvaccinated against the pandemic 2009-2011 H1N1 influenza virus in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Deise Nascimento de Freitas

    2015-10-01

    Full Text Available ABSTRACTINTRODUCTION:While no single factor is sufficient to guarantee the success of influenza vaccine programs, knowledge of the levels of immunity in local populations is critical. Here, we analyzed influenza immunity in a population from Southern Brazil, a region with weather conditions that are distinct from those in the rest of country, where influenza infections are endemic, and where greater than 50% of the population is vaccinated annually.METHODS:Peripheral blood mononuclear cells were isolated from 40 individuals. Of these, 20 had received the H1N1 vaccine, while the remaining 20 were unvaccinated against the disease. Cells were stimulated in vitro with the trivalent post-pandemic influenza vaccine or with conserved major histocompatibility complex I (MHC I peptides derived from hemagglutinin and neuraminidase. Cell viability was then analyzed by [3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide]-based colorimetric assay (MTT, and culture supernatants were assayed for helper T type 1 (Th1 and Th2-specific cytokine levels.RESULTS:Peripheral blood lymphocytes from vaccinated, but not unvaccinated, individuals exhibited significant proliferation in vitro in the presence of a cognate influenza antigen. After culturing with vaccine antigens, cells from vaccinated individuals produced similar levels of interleukin (IL-10 and interferon (IFN-γ, while those from unvaccinated individuals produced higher levels of IFN-γ than of IL-10.CONCLUSIONS:Our data indicate that peripheral blood lymphocytes from vaccinated individuals are stimulated upon encountering a cognate antigen, but did not support the hypothesis that cross-reactive responses related to previous infections can ameliorate the immune response. Moreover, monitoring IL-10 production in vaccinated individuals could comprise a valuable tool for predicting disease evolution.

  13. Comparable effects of 1800- and 2400-rad (18- and 24-Gy) cranial irradiation on height and weight in children treated for acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Starceski, P.J.; Lee, P.A.; Blatt, J.; Finegold, D.; Brown, D.

    1987-01-01

    To examine the effects of low-dose cranial irradiation on growth and to determine if one can predict patients in whom growth will be most affected, we studied 47 children with acute lymphocytic leukemia who had been treated with 2400 rad (24 Gy), 1800 rad (18 Gy), or no whole-brain irradiation. Serial measurements of height, weight, and weight for height were obtained by retrospective chart review. The effects of 1800 rad (18 Gy) and 2400 rad (24 Gy) treatment were indistinguishable. Height percentiles among irradiated patients decreased by a mean of 12% six months after diagnosis, and growth generally did not catch up. Moreover, although 33 irradiated patients maintained heights within the normal range, In 11 patients (33%) a dramatic falloff occurred such that by three years following diagnosis their height for age was more than 30 percentiles below the original value. These patients were all identifiable at six months since their height percentiles had already decreased by more than 15%. Although weight percentiles did not change following irradiation, the weight-for-height ratio increased and patients were relatively stockier three years after therapy than they had been at diagnosis. In patients who had received chemotherapy alone, the weight-for-height ratio also increased, but this appeared to be due to a disproportionate increase in weight. Longer follow-up and evaluation of larger cohorts of patients treated with 1800 rad (18 Gy) will be needed to confirm these results

  14. Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

    Science.gov (United States)

    Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

    2018-01-01

    Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

  15. 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.

  16. 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.

  17. 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

  18. 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).

  19. 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...

  20. 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 ...

  1. Flow cytometric immunophenotyping of regulatory T cells in chronic lymphocytic leukemia: comparative assessment of various markers and use of novel antibody panel with CD127 as alternative to transcription factor FoxP3.

    Science.gov (United States)

    Dasgupta, Alakananda; Mahapatra, Manoranjan; Saxena, Renu

    2013-04-01

    This study analyzed the frequency of regulatory T cells (Tregs) in chronic lymphocytic leukemia (CLL) by multiparameter flow cytometric immunophenotyping. Patients showed significantly increased frequencies of Tregs as compared to controls, a significantly higher percentage than that identified by previous studies, possibly indicating a different prognosis of CLL in different parts of the world and, more precisely, a worse prognosis of CLL in the Indian population. A higher frequency of Tregs was also seen in advanced stage of disease with significantly reduced frequencies of Tregs in patients with CLL after chemotherapy. A significant proportion of CD127low/-FoxP3+ Tregs expressed only low levels of CD25. Thus, CD127 appears to be a better marker than CD25 for the identification of CD4+FoxP3+ T cells as potential Tregs. Our results suggest that the specificity and sensitivity of CD4+CD127low/- cells are comparable to those of CD4+FoxP3+, which is the gold standard, and can be used as an alternative. This novel flow cytometric antibody panel with fewer number of antibodies is cost-effective and can be used to enumerate Tregs in resource-limited settings.

  2. Comparing of Cu/Zn SOD Gene Expression of Lymphocyte Cell and Malondialdehyde Level in Active Men and Women after Physical Training

    Directory of Open Access Journals (Sweden)

    Bakhtiar Tartibian

    2012-07-01

    Full Text Available Background: The purpose of this study is to compare Cu/Zn SOD mRNA and MDA level as a result of a session incremental exercise in active women and men. Materials and Methods: This research is a quasi-experimental study with repeated measurements in which 14 active female and 13 male subjects with age range 22-24 participated voluntarily. Then, blood was taken from brachial vein of the subjects in three stages before and after GXT (Graded exercise test and 3 hours after that and SYBER Green PCR Master mix reagent Kit and Real time-PCR were used to measure Cu/Zn SOD mRNA and spectrophotometer was used to measure MDA level.Results: MDA levels increased significantly in men during the recovery stage and after the exercise (p1=0.012 and p2 =0.014, but it did not increase significantly in active women. Also, MDA difference between the two genders was not reported significant in any of the exercise stages. Cu/Zn SOD gene expression did not increase significantly in either sex.Conclusion: The risk of injury from free radicals is more probable in active men than active women and vigorous physical activity does not significantly increase the Cu/Zn SOD gene expression.

  3. Comparative studies of the dose-response relationship of radiation-induced chromosomal aberrations in human lymphocytes induced by low radiation doses, using Feulgen orcein glacial acetic acid and FPG staining

    International Nuclear Information System (INIS)

    Wagner, R.

    1982-01-01

    Peripheral lymphocytes were exposed in vitro to 220 kV X-radiation, with doses of 0.05, 0.1, 0.2, 0.4, and 0.5 Gy, their culture and preparation was made under standardized conditions. The slides were stained using two different methods, namely FPG staining (fluorescence plus giemsa), and the conventional Feulgen orcein glacial acetic acid method. Compared to the conventional method, FPG staining achieved absolute yields of acentric fragments three times higher, and of dicentric chromosomes twice as high. A linear dose-response relationship in acentric fragments was found by the two staining methods alike, which agrees with the theory. Both staining methods revealed a linear-square dose-response relationship in dicentric chromosomes. Using FPG staining, preparing only M 1 cells for evaluation, the linear component was found to be dominant over the whole dose range applied. The conventional method, analysing M 1 and M 2 cells, revealed the square component to be the most important one. The dose-response relationships determined after FPG staining can be used for biological dosimetry. Calibration can be improved by increasing the number of cells analysed at doses [de

  4. Role of the B-cell receptor in chronic lymphocytic leukemia: where do we stand?

    Science.gov (United States)

    Fais, Franco; Bruno, Silvia; Ghiotto, Fabio

    2010-01-01

    The past 15 years have witnessed an enormous effort in studying B-cell Chronic Lymphocytic Leukemia. A great number of researches brought significant novel information and a better understanding of the natural history of this disease. This mini review will focus on the studies related to the Immunoglobulin variable (IgV) genes rearrangements that compose the B-cell receptor (BcR) of the leukemic clones. These studies have defined a role for the antigen(s) in the paths that lead to leukemic clone generation/expansion and underscore the informative value represented by BcR analyses.

  5. 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

  6. Cloning and expression of canine CD25 for validation of an anti-human CD25 antibody to compare T regulatory lymphocytes in healthy dogs and dogs with osteosarcoma.

    Science.gov (United States)

    Rissetto, K C; Rindt, H; Selting, K A; Villamil, J A; Henry, C J; Reinero, C R

    2010-05-15

    T regulatory cells (Tregs) are a unique subset of T helper cells that serve to modify/inhibit effector cells of the immune system and thus are essential to prevent autoimmunity. Overzealous Treg activity may contribute to impaired immune responses to cancer. Tregs can be phenotypically identified by proteins expressed on the cell surface (CD4 and CD25) and inside the cell (forkhead box3 (FoxP3)), although in dogs, no anti-canine CD25 antibody exists. We hypothesized that a mouse anti-human CD25 antibody definitively recognizes the canine protein and can be used to identify Tregs in dogs. We describe cloning and transfection of the canine CD25 gene into human HeLa cells with subsequent expression of the canine protein on the cell surface detected using an anti-human CD25 antibody in a flow cytometric assay. Validation of this antibody was used to identify CD4+CD25+FoxP3+ Tregs in 39 healthy dogs and 16 dogs with osteosarcoma (OSA). Results were expressed in five different ways and showed significantly fewer %CD4+CD25+ T lymphocytes expressing FoxP3 in blood of older dogs (>/=7 years) compared with the other two age groups (<2 and 2-6 years) (p<0.001) and fewer %CD4+CD25+FoxP3+ Tregs in the tumor draining lymph nodes of OSA patients compared to the unrelated lymph node (p=0.049). However, there was no significant difference in % Tregs in the peripheral blood or lymph nodes between the control dogs and those with OSA. While the CD25 antibody can be successfully used in a flow cytometric assay to identify Tregs, this study does not support clinical utility of phenotypic recognition of Tregs in dogs with OSA. Copyright 2010 Elsevier B.V. All rights reserved.

  7. 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

  8. 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.)

  9. 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

  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. 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...

  13. 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)

  14. 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.

  15. Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf of the infectious diseases and acute leukemia working parties of the EBMT.

    Science.gov (United States)

    Cesaro, Simone; Crocchiolo, Roberto; Tridello, Gloria; Knelange, Nina; Van Lint, Maria Teresa; Koc, Yener; Ciceri, Fabio; Gülbas, Zafer; Tischer, Johanna; Afanasyev, Boris; Bruno, Benedetto; Castagna, Luca; Blaise, Didier; Mohty, Mohamad; Irrera, Giuseppe; Diez-Martin, J L; Pierelli, Luca; Pioltelli, Pietro; Arat, Mutlu; Delia, Mario; Fagioli, Franca; Ehninger, Gerhard; Aljurf, Mahmoud; Carella, Angelo Michele; Ozdogu, Hakan; Mikulska, Malgorzata; Ljungman, Per; Nagler, Arnon; Styczynski, Jan

    2018-04-01

    The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+ and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI: 50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other main outcomes were comparable. No difference in NRM nor OS was observed after stratification for the intensity of conditioning and multivariate anaysis confirmed the lack of significant association with NRM or OS. In conclusion, the choice of a CMV-seronegative donor did not impair early survival of CMV-seropositive patients with acute leukemia after a first, non T-cell depleted haploidentical HSCT and PT-Cy among this series of 983 consecutive patients. Future research may focus on the assessment of the hierarchy of all the donor variables.

  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. 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 ...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. COMPAR

    International Nuclear Information System (INIS)

    Kuefner, K.

    1976-01-01

    COMPAR works on FORTRAN arrays with four indices: A = A(i,j,k,l) where, for each fixed k 0 ,l 0 , only the 'plane' [A(i,j,k 0 ,l 0 ), i = 1, isub(max), j = 1, jsub(max)] is held in fast memory. Given two arrays A, B of this type COMPAR has the capability to 1) re-norm A and B ind different ways; 2) calculate the deviations epsilon defined as epsilon(i,j,k,l): =[A(i,j,k,l) - B(i,j,k,l)] / GEW(i,j,k,l) where GEW (i,j,k,l) may be chosen in three different ways; 3) calculate mean, standard deviation and maximum in the array epsilon (by several intermediate stages); 4) determine traverses in the array epsilon; 5) plot these traverses by a printer; 6) simplify plots of these traverses by the PLOTEASY-system by creating input data blocks for this system. The main application of COMPAR is given (so far) by the comparison of two- and three-dimensional multigroup neutron flux-fields. (orig.) [de

  3. Enterocolic lymphocytic phlebitis: statistical analysis of histology features in viable and ischemic bowel.

    Science.gov (United States)

    Medlicott, Shaun A C; Guggisberg, Kelly A; DesCôteaux, Jean-Gaston; Beck, Paul

    2006-07-01

    Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Myointimal hyperplasia may represent a chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600 submucosal and subserosal veins from both ischemic and intact bowel segments to discern if vascular morphology varied between sites. Crescentic and circumferential lymphocytic phlebitis is more common in viable bowel than in the ischemic segment. A nonsignificant trend was found for increased crescentic morphology between intact bowel remote from the ischemic focus compared with that adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly different in viable and ischemic bowel, changing from the classic lymphocytic to necrotizing lesions respectively.

  4. Inactivation of hemopoietic stem cells by lymphocytes as related to genotype of interacting cells

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R V; Seslavina, L S; Panteleev, E I; Egorova, O S

    1975-05-01

    Inoculation of a mixture of bone marrow cells with allogeneic lymphocytes into irradiated mice of inbred strains or into F/sub 1/ hybrids results in the depression of bone marrow cell proliferation in the spleen of the recipient: the effect of inactivation of nonsyngeneic stem cells. The inactivation of stem cells by allogeneic lymphocytes can be detected in all tested combinations of mice strains - donors of lymphocytes and bone marrow cells and mice - recipients but the degree of inactivation differs and depends on the genotype of cell donors rather than on the genotype of the recipient. Lymphocytes of some mice strains (haplotypes H-2sup(k) and H-2sup(a)) are more active killers of bone marrow cells as compared with lymphocytes of other strains (hyplotypes H-2sup(b) and H-2sup(d)). Probably, the degree of stem cells inactivation by lymphocytes depends on the differences of their histocompatibility in H-2 system.

  5. Childhood Leukemia--A Look at the Past, the Present and the Future.

    Science.gov (United States)

    Findeisen, Regina; Barber, William H.

    1997-01-01

    Provides an overview of childhood leukemia. The causes, the survival period, different types (acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and hairy cell leukemia), symptoms, treatment, side effects of treatment (including learning problems), and the expected future direction of…

  6. Evidence for the replication of bovine leukemia virus in the B lymphocytes

    International Nuclear Information System (INIS)

    Paul, P.S.; Pomeroy, K.A.; Johnson, D.W.; Muscoplat, C.C.; Handwerger, B.S.; Soper, F.F.; Sorensen, D.K.

    1977-01-01

    Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells

  7. Treatments for chronic myeloid leukemia: a qualitative systematic review

    Directory of Open Access Journals (Sweden)

    Ferdin

    2012-08-01

    Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response

  8. [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.

  9. 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...

  10. 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.

  11. 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

  12. A rapid radioassay for human IgG produced in lymphocyte in vitro culture systems

    International Nuclear Information System (INIS)

    Weightman, D.R.; Shale, D.J.; Tomlinson, W.R.

    1981-01-01

    Protein A bearing Staphylococcus aureus was used to develop a solid-phase radioassay for IgG immunoglobulins. The assay was specifically optimised for use in vitro human lymphocyte culture work. Compared with a solid-phase radioimmunoassay for IgG produced in lymphocyte culture, this assay had a similar performance profile and the advantages of rapidity and technical ease. (Auth.)

  13. Differentiation of peripheral lymphocyte population in Pu-exposed beagle dogs

    International Nuclear Information System (INIS)

    Morris, J.E.

    1977-01-01

    The percentage of peripheral lymphocytes binding fluorescent-labeled anticanine antibodies was measured in plutonium-oxide-exposed and unexposed beagle dogs. With this assay system, there was a significant decrease in the percentage of lymphocytes binding the labeled antibody in exposed animals compared to control animals

  14. Caspase Cleavages of the Lymphocyte-oriented Kinase Prevent Ezrin, Radixin, and Moesin Phosphorylation during Apoptosis*

    Science.gov (United States)

    Leroy, Catherine; Belkina, Natalya V.; Long, Thavy; Deruy, Emeric; Dissous, Colette; Shaw, Stephen; Tulasne, David

    2016-01-01

    The lymphocyte-oriented kinase (LOK), also called serine threonine kinase 10 (STK10), is synthesized mainly in lymphocytes. It is involved in lymphocyte migration and polarization and can phosphorylate ezrin, radixin, and moesin (the ERM proteins). In a T lymphocyte cell line and in purified human lymphocytes, we found LOK to be cleaved by caspases during apoptosis. The first cleavage occurs at aspartic residue 332, located between the kinase domain and the coiled-coil regulation domain. This cleavage generates an N-terminal fragment, p50 N-LOK, containing the kinase domain and a C-terminal fragment, which is further cleaved during apoptosis. Although these cleavages preserve the entire kinase domain, p50 N-LOK displays no kinase activity. In apoptotic lymphocytes, caspase cleavages of LOK are concomitant with a decrease in ERM phosphorylation. When non-apoptotic lymphocytes from mice with homozygous and heterozygous LOK knockout were compared, the latter showed a higher level of ERM phosphorylation, but when apoptosis was induced, LOK−/− and LOK+/− lymphocytes showed the same low level, confirming in vivo that LOK-induced ERM phosphorylation is prevented during lymphocyte apoptosis. Our results demonstrate that cleavage of LOK during apoptosis abolishes its kinase activity, causing a decrease in ERM phosphorylation, crucial to the role of the ERM proteins in linking the plasma membrane to actin filaments. PMID:26945071

  15. Caspase Cleavages of the Lymphocyte-oriented Kinase Prevent Ezrin, Radixin, and Moesin Phosphorylation during Apoptosis.

    Science.gov (United States)

    Leroy, Catherine; Belkina, Natalya V; Long, Thavy; Deruy, Emeric; Dissous, Colette; Shaw, Stephen; Tulasne, David

    2016-05-06

    The lymphocyte-oriented kinase (LOK), also called serine threonine kinase 10 (STK10), is synthesized mainly in lymphocytes. It is involved in lymphocyte migration and polarization and can phosphorylate ezrin, radixin, and moesin (the ERM proteins). In a T lymphocyte cell line and in purified human lymphocytes, we found LOK to be cleaved by caspases during apoptosis. The first cleavage occurs at aspartic residue 332, located between the kinase domain and the coiled-coil regulation domain. This cleavage generates an N-terminal fragment, p50 N-LOK, containing the kinase domain and a C-terminal fragment, which is further cleaved during apoptosis. Although these cleavages preserve the entire kinase domain, p50 N-LOK displays no kinase activity. In apoptotic lymphocytes, caspase cleavages of LOK are concomitant with a decrease in ERM phosphorylation. When non-apoptotic lymphocytes from mice with homozygous and heterozygous LOK knockout were compared, the latter showed a higher level of ERM phosphorylation, but when apoptosis was induced, LOK(-/-) and LOK(+/-) lymphocytes showed the same low level, confirming in vivo that LOK-induced ERM phosphorylation is prevented during lymphocyte apoptosis. Our results demonstrate that cleavage of LOK during apoptosis abolishes its kinase activity, causing a decrease in ERM phosphorylation, crucial to the role of the ERM proteins in linking the plasma membrane to actin filaments. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.)

  1. 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

  2. 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.

  3. 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

  4. [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

  5. Application of rosula-formation tests for determining man lymphocyte radiosensitivity

    International Nuclear Information System (INIS)

    Shchilik, Ts.; Krushevskij, E.; Endrzhejchak, V.

    1982-01-01

    Radiosensitivity of subpopulation of lymphocytes-T-lymphocytes and B-lymphocytes was studied to diagnose acute radiation disease as well as if radiosensitivity of any of them is more effective indication of irradiation as compared with absolute lymphocyte quantity. The investigations were carried on in vitro using blood of healthy men-donors at the age of 21-25. It is shown that absolute quantity of cells forming AE rosette in perapheral blood is a much better indication of irradiation as compared with absolute quantity of lymphocytes. Considerable significance of tests of rosette formation especially AE test is underlined. High test sensitivity and relative simplicity of accomplishment permit authors to recommend it for diagnostic purposes when revealing acute radiation disease including the stages of medicinal evacuation

  6. 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.

  7. 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.

  8. 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.

  9. Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

    DEFF Research Database (Denmark)

    Ellingsen, A R; Sørensen, F B; Larsen, Jytte Overgaard

    2001-01-01

    with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared......Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin...... with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically...

  10. 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)

  11. Decreased circulating T regulatory lymphocytes in obese patients undergoing bariatric surgery.

    Science.gov (United States)

    Agabiti-Rosei, Claudia; Trapletti, Valentina; Piantoni, Silvia; Airò, Paolo; Tincani, Angela; De Ciuceis, Carolina; Rossini, Claudia; Mittempergher, Francesco; Titi, Amin; Portolani, Nazario; Caletti, Stefano; Coschignano, Maria Antonietta; Porteri, Enzo; Tiberio, Guido A M; Pileri, Paola; Solaini, Leonardo; Kumar, Rajesh; Ministrini, Silvia; Agabiti Rosei, Enrico; Rizzoni, Damiano

    2018-01-01

    It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while T-regulatory (Treg) lymphocytes seem to be protective in this regard. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed. We have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 12 hypertensive lean subjects undergoing an elective surgical intervention. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and Treg lymphocytes. A marked reduction of several Treg subpopulations was observed in obese patients compared with controls, together with an increased in CD4+ effector memory T-effector cells. In severely obese patients, Treg lymphocytes are clearly reduced and CD4+ effector memory cells are increased. It may be hypothesized that they might contribute to the development of marked microvascular alterations previously observed in these patients.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  13. 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

  14. 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.

  15. 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)

  16. 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.)

  17. 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.

  18. Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ceren Günel

    2015-04-01

    Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. Predictive radiosensitivity tests in human lymphocytes

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  4. 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...

  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. Emergency splenectomy for trauma in the setting of splenomegaly, axillary lymphadenopathy, and incidental B-cell chronic lymphocytic leukemia: A case report

    Directory of Open Access Journals (Sweden)

    Rodolfo J. Oviedo, MD, FACS

    2017-01-01

    Conclusion: An emergency splenectomy is an appropriate operative intervention for a grade V splenic laceration with hemoperitoneum, splenomegaly, and axillary lymphadenopathy regardless of the potential for a neoplastic process such as B-cell CLL. Post-splenectomy vaccinations and oncologic follow-up for systemic chemotherapy should be facilitated after recovery.

  8. 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.

  9. 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

  10. 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.

  11. Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

    Science.gov (United States)

    Jessop, J J; Gale, K; Bayer, B M

    1988-01-01

    The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

  12. The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients

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    Serap Yalçın

    2015-12-01

    Full Text Available Objective: Interleukin-18 (IL-18 is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL and chronic myelogenous leukemias (CML in Turkish patients. Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T, rs5744227(C/G, rs5744228(A/G, and rs187238(G/C were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. Results: Significant associations were detected between the IL-18 rs187238(G/C polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T, rs5744227(C/G, or rs5744228(A/G polymorphisms and CLL or CML. Conclusions: IL-18 gene promoter rs187238(G/C polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML. Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.

  13. Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function.

    Science.gov (United States)

    McGregor, Bonnie A; Murphy, Karly M; Albano, Denise L; Ceballos, Rachel M

    2016-01-01

    Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol, and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first-year graduate students (n = 22) and a community control sample (n = 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19 + B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19 + B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19 + lymphocytes.

  14. [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.

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

    Science.gov (United States)

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

    2009-06-01

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

  16. 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.

  17. 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.

  18. Relations between the stimulation of mixed lymphocyte populations and the staging system according Rai in patients with chronic lymphatic leukemia

    International Nuclear Information System (INIS)

    Heilmann, E.; Venne, U.

    1979-01-01

    By means of the incorporation rate of 3 H thymidine into the lymphocytes of patients with chronic lymphatic leukemia the possibility of stimulating them by using different mitogens was checked and compared with normal persons. The examination covered 11 patients treated with extracorporeal irradiation of the blood (ECIB), 5 patients treated with a chlorambucil therapy, and 10 untreated patients who where classified according to the staging system proposed by Rai. The lymphocytes of the peripheral blood were stimulated as mixed and isolated T and B-lymphocytes in the microculture by using the mitogens PHA, PWM, ConA, and LPS. In all CLL patients there was a diminished stimulation rate of a mixed lymphocyte population. A relation existed between the seriousness of the stage and the deminution of the incorporation rate of 3 H thymidine. A corresponding correlation could not be identified in untreated CLL patients. Isolated T-lymphocytes revealed better results of stimulation than the total population. As to their function B-lymphocytes showed a dependence on the kind of therapy. In the mixed lymphocyte culture of normal persons the best findings could be observed after stimulation with PHA, that is also valid for CLL patients. PHA, PWA, ConA, and LPS were suitable as substances stimulating B-lymphocytes with different efficacy in normal persons and CLL patients. Both collectives showed the best results in the T-lymphocyte culture after stimulation with LPS. (author)

  19. Evolution and phylogeny of B lymphocytes

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    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.

  20. Lymphocytic Pleural Effusion in Acute Melioidosis

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    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.

  1. The Influence of N-acetylcysteine and Gender-Related Differences on the Radiosensitivity of Mouse Lymphocytes

    International Nuclear Information System (INIS)

    El-Shamy, E.; El-Kabany, H.

    2012-01-01

    The objective of the present study is to evaluate the possible efficiency of 200 mg/kg body weight N-acetylcysteine (NAC) on the radiosensitivity of mouse lymphocytes considering gender factor. The half of blood sample from mice was exposed to gamma-radiation (2 Gy). The time course of lymphocyte apotosis of irradiated samples was examined in vitro by flow cytometry and compared with lymphocytes from non-irradiated remaining half of samples. Kinetics of radiation-induced apoptosis was similar among groups, which peaked at 8 h. NAC protected irradiated lymphocytes in male mice. Lymphocytes from female mice were highly radiation resistant compared to males and the NAC provided no additional benefit at the doses used in this study. These results highlight that radiation-induced apoptosis is complex and is modified by the radio protector and gender.

  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. 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.

  4. 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)

  5. Repair of single-strand breaks in normal and trisomic lymphocytes

    International Nuclear Information System (INIS)

    Leonard, J.C.; Merz, T.

    1982-01-01

    Recently, Athanasiou and colleagues (1981) reported a deficiency in the capacity of lymphocytes from persons with Down's syndrome to repair single-strand DNA breaks. They found that 1 h after exposure to 160 Gray, repair processes had restored the sedimentation profile of DNA from normal lymphocytes to control values, whereas the relative average molecular weight of DNA from irradiated lymphocytes from persons with Down's syndrome showed no increase during the repair interval. They have suggested that their data, in conjunction with the earlier data concerning the frequencies of induced chromosomal aberrations in lymphocytes from persons with Down's syndrome, reflect a decreased efficiency in some aspect of DNA repair in trisomic cells. However, for further studies of this hypothesis, it is more appropriate to study the rejoining of DNA single-strand breaks after doses comparable to those used in tests for chromosomal aberrations. (orig.)

  6. Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Toyohira, Ken; Yasumoto, Kosei; Manabe, Hideo; Ohta, Mitsuo; Terashima, Hiromi

    1979-01-01

    Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I and II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size. (author)

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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

  11. 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

  12. An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations[S

    Science.gov (United States)

    Romano, Maria; Di Taranto, Maria Donata; Mirabelli, Peppino; D'Agostino, Maria Nicoletta; Iannuzzi, Arcangelo; Marotta, Gennaro; Gentile, Marco; Raia, Maddalena; Di Noto, Rosa; Del Vecchio, Luigi; Rubba, Paolo; Fortunato, Giuliana

    2011-01-01

    The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes. PMID:21865347

  13. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation.

    Science.gov (United States)

    Belkina, Natalya V; Liu, Yin; Hao, Jian-Jiang; Karasuyama, Hajime; Shaw, Stephen

    2009-03-24

    ERM (ezrin-radixin-moesin) proteins mediate linkage of actin cytoskeleton to plasma membrane in many cells. ERM activity is regulated in part by phosphorylation at a C-terminal threonine, but the identity of ERM kinases is unknown in lymphocytes and incompletely defined in other mammalian cells. Our studies show that lymphocyte-oriented kinase (LOK) is an ERM kinase in vitro and in vivo. Mass spectrometric analysis indicates LOK is abundant at the lymphocyte plasma membrane and immunofluorescence studies show LOK enrichment at the plasma membrane near ERM. In vitro peptide specificity analyses characterize LOK as a basophilic kinase whose optimal substrate sequence resembles the ERM site, including unusual preference for tyrosine at P-2. LOK's activity on moesin peptide and protein was comparable to reported ERM kinases ROCK and PKC but unlike them LOK displayed preferential specificity for moesin compared to traditional basophilic kinase substrates. Two genetic approaches demonstrate a role for LOK in ERM phosphorylation: cell transfection with LOK kinase domain augments ERM phosphorylation and lymphocytes from LOK knockout mice have >50% reduction in ERM phosphorylation. The findings on localization and specificity argue that LOK is a direct ERM kinase. The knockout mice have normal hematopoietic cell development but notably lymphocyte migration and polarization in response to chemokine are enhanced. These functional alterations fit the current understanding of the role of ERM phosphorylation in regulating cortical reorganization. Thus, these studies identify a new ERM kinase of importance in lymphocytes and confirm the role of ERM phosphorylation in regulating cell shape and motility.

  14. 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.

  15. 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.

  16. 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)

  17. Prediction of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma by Using Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio.

    Science.gov (United States)

    Ozgonul, Cem; Sertoglu, Erdim; Mumcuoglu, Tarkan; Ozge, Gokhan; Gokce, Gokcen

    2016-12-01

    To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls. In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection. There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024). Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.

  18. 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.

  19. The effect of smoking on neutrophil/lymphocyte and platelet/lymphocyte ratio and platelet ındices: a retrospective study.

    Science.gov (United States)

    Tulgar, Y K; Cakar, S; Tulgar, S; Dalkilic, O; Cakiroglu, B; Uyanik, B S

    2016-07-01

    Smoking commonly leads to death. Although the neutrophil/lymphocyte Ratio, platelet/lymphocyte ratio and platelet indices have been shown to be important for the diagnosis, prognosis and severity of some diseases, the smoking status of patients in these studies has not been well defined. In this study, we compared ratios derived from complete blood count and platelet indices to smoking status and length in smokers and non-smokers. The data of healthy males and females aged between 18-60 years who presented to our institute for a routine check-up were collected, and subjects were divided in two groups - smokers and non-smokers. The presence of medical history or laboratory results which could affect inflammatory response, formed our exclusion criteria. All complete blood count results were noted and persons' smoking habits were calculated as pack/years. White blood cell, neutrophil, basophil and eosinophil counts; mean corpuscular volume, red cell distribution width and neutrophil/lymphocyte ratio were significantly higher in smokers when compared to non-smokers (psmokers were grouped according to smoking habits; positive linear correlations were detected between pack/year and Neutrophil/lymphocyte ratio and also pack/year and plateletcrit in smokers (paffected and platelet distribution width is increased in smokers. If smokers are not excluded from studies evaluating neutrophil/lymphocyte ratio and platelet distribution width, the relationship between smoking status as well as pack/year must be determined and reported.

  20. 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

  1. 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)

  2. Micronuclei in lymphocytes from currently active uranium miners

    International Nuclear Information System (INIS)

    Zoelzer, Friedo; Freitinger Skalicka, Zuzana; Havrankova, Renata; Hon, Zdenek; Rosina, Jozef; Navratil, Leos; Skopek, Jiri

    2012-01-01

    Micronuclei can be used as markers of past radiation exposure, but only few studies have dealt with uranium miners. In this paper, we report on micronuclei in lymphocytes from individuals currently working at Rozna, Czech Republic, the last functioning uranium mine in the European Union. A modified micronucleus-centromere test was applied to assess the occurrence of micronuclei in stimulated lymphocytes, as well as their content in terms of whole chromosomes or fragments. Compared with unexposed individuals, the miners had higher frequencies of micronucleus-containing lymphocytes and higher percentages of micronuclei without centromeres, and the differences were significant for both parameters (0.74 ± 0.60 vs. 0.50 ± 0.42, p = 0.017 and 49 ± 44 vs. 12 ± 21, p = 0.0002; means ± standard deviations). There were also significant correlations between one or other of these parameters on the one hand and various dose values on the other, in particular with a 'retrievable' dose, that is, a dose whose effect should still be recognisable in lymphocytes assuming a half-life of 3 years. The 'retrievable' dose at which a doubling of the micronucleus frequency was observed was around 35 mSv, corresponding to a total dose of 90 mSv received while working in the mines. Altogether, our data show that the micronucleus-centromere test is a valuable tool for the assessment of past radiation exposure in uranium miners. The scatter in the data is of course far too great to allow individual dosimetry, but for groups of a few dozen exposed individuals, the method can be used to monitor doses clearly below 100 mSv. (orig.)

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

    International Nuclear Information System (INIS)

    Martin, C.; Romero, S.; Arriero, J.M.; Hernandez, L.; Sanchez-Paya, J.; Massuti, B.

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Brian I., E-mail: brianicarr@hotmail.com [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy); Metes, Diana M. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy)

    2012-03-01

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

  6. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    2010-08-01

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  7. CD4+ LYMPHOCYTES IMPROVE VENOUS BLOOD FLOW IN EXPERIMENTAL ARTERIOVENOUS FISTULAE

    Science.gov (United States)

    Duque, Juan C.; Martinez, Laisel; Mesa, Annia; Wei, Yuntao; Tabbara, Marwan; Salman, Loay H.; Vazquez-Padron, Roberto I.

    2015-01-01

    Background The role of immune cells in arteriovenous fistulae (AVF) maturation is poorly understood and has received, until quite recently, little attention. This study examines the role of T lymphocytes in AVF vascular remodeling. Methods Experimental fistulae were created in athymic rnu nude rats lacking mature T lymphocytes and euthymic control animals by anastomosing the left superior epigastric vein to the nearby femoral artery. Blood flow rates, wall morphology and histological changes were assessed in AVF 21 days after creation. The effect of CD4+ lymphocytes on AVF maturation in athymic animals was analyzed by adoptive transfer of cells after fistula creation. Results The absence of T lymphocytes compromised blood flow in experimental fistulae. Histopathological inspection of AVF from athymic rats revealed that T cell immunodeficiency negatively affected venous vascular remodeling, as evidenced by a reduced lumen, a thick muscular layer and a low number of inflammatory cells compared to control animals. Adoptive transfer of CD4+ lymphocytes from euthymic rats into athymic animals before and after fistula creation improved blood flow and reduced intima-media thickness. Conclusion These results point at the protective role of CD4+ lymphocytes in the remodeling of the AVF vascular wall. PMID:25999254

  8. Time-dependent changes in rat lymphocyte activity in response to isolation

    International Nuclear Information System (INIS)

    Jessop, J.J.; Bayer, B.M.

    1986-01-01

    The authors have found that isolation of rats, previously adapted to group-housing conditions, resulted in time-dependent changes in mitogenic and cytolytic responses of lymphocytes. A depression (40-60%) of the uptake of 3 H-thymidine by splenic and blood lymphocytes stimulated with either phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was observed during the first 48 hours after transfer of the animals to individual cages. Within 4 days the mitogenic response increased and was comparable to that of animals which had been continuously group-housed. The response continued to increase and by 10 days was enhanced by 2 to 4 fold and remained elevated for at least 8 weeks. Similar changes in activity were observed with both splenic and blood lymphocytes, however, thymic lymphocytes taken from isolated animals demonstrated no change in reactivity to PHA. As with mitogenic responses, the cytolytic activity of splenic lymphocytes was also depressed during the initial days of isolation and as isolation continued, the activity returned to normal and was significantly enhanced (80%) within 5 weeks. These data show that changes in lymphocyte activity are dependent on the duration of exposure to isolated housing conditions and may be a part of the acute, adaptive and chronic phases of the response of rats to the stress of isolation

  9. Increased rate of repair of ultraviolet-induced DNA strand breaks in mitogen stimulated lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, S.M.; Lavin, M.F.; Jennings, P.A. (Queensland Univ., St. Lucia (Australia). Dept. of Biochemistry; Queensland Univ., St. Lucia (Australia). Dept. of Veterinary Pathology; Queensland Univ. St. Lucia (Australia). Dept. of Public Health)

    1982-05-01

    Previous results have shown that phytohaemagglutinin-stimulated bovine lymphocytes exhibit a peak of ultraviolet-induced DNA repair synthesis 3 to 4 days after addition of mitogen. The level of repair synthesis was approximately tenfold higher than that in unstimulated lymphocytes. These studies have been extended to examine the rate of repair of strand breaks in U.V.-irradiated bovine lymphocytes. The extent of breakage of DNA was shown to be the same in mitogen-stimulated and unstimulated lymphocytes from two breeds of cattle, when determined by sedimentation of nucleoids on sucrose gradients. However, in mitogen-stimulated cells the time taken to repair DNA strand breaks was 6 hours compared with 12 hours in stationary phase lymphocytes after a U.V. dose of 5 J/m/sup 2/. These results suggest that the increased rate of repair of strand breaks is due to the induction of enzymes involved at the post-incision stage of DNA repair. Thus the increased level of repair synthesis observed in earlier work correlates with an increased rate of repair of DNA strand breaks in phytohaemagglutinin-stimulated bovine lymphocytes.

  10. Increased rate of repair of ultraviolet-induced DNA strand breaks in mitogen stimulated lymphocytes

    International Nuclear Information System (INIS)

    Hamlet, S.M.; Lavin, M.F.; Jennings, P.A.; Queensland Univ., St. Lucia; Queensland Univ. St. Lucia

    1982-01-01

    Previous results have shown that phytohaemagglutinin-stimulated bovine lymphocytes exhibit a peak of ultraviolet-induced DNA repair synthesis 3 to 4 days after addition of mitogen. The level of repair synthesis was approximately tenfold higher than that in unstimulated lymphocytes. These studies have been extended to examine the rate of repair of strand breaks in U.V.-irradiated bovine lymphocytes. The extent of breakage of DNA was shown to be the same in mitogen-stimulated and unstimulated lymphocytes from two breeds of cattle, when determined by sedimentation of nucleoids on sucrose gradients. However, in mitogen-stimulated cells the time taken to repair DNA strand breaks was 6 hours compared with 12 hours in stationary phase lymphocytes after a U.V. dose of 5 J/m 2 . These results suggest that the increased rate of repair of strand breaks is due to the induction of enzymes involved at the post-incision stage of DNA repair. Thus the increased level of repair synthesis observed in earlier work correlates with an increased rate of repair of DNA strand breaks in phytohaemagglutinin-stimulated bovine lymphocytes. (author)

  11. 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.

  12. 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.

  13. Changes in lymphocyte subsets due to local irradiation of a portion of the maxilla in mice. A study of minor population lymphocytes

    International Nuclear Information System (INIS)

    Yamashita, Chiho; Satoh, Daigo; Yosue, Takashi

    2001-01-01

    In the present study we investigates the influence of the local irradiation of a portion of the maxilla on the numbers of lymphocyte subsets in peripheral blood and spleen, specifically minor population lymphocytes (γδT cells and NKT cells). Male C57BL/6 mice at 15 weeks of age were used for the experiments. In the irradiation group, a portion of the maxilla was exposed to X-ray (2.0 Gy/min, 10 Gy) and we analyzed lymphocytes using flow cytometry (anti-CD3, CD4, CD8, TCRαβ, TCRγδ and NK1.1 monoclonal antibodies), and compared the outcome to that obtained from the non-irradiation groups. The following results were obtained: In peripheral blood, CD4 + SP T cells, CD8 + SP T cells, αβ T cells, γδ T cells and NK cells decreased significantly on the first day and third day after irradiation. NKT cells decreased significantly on the third day after irradiation. In spleen, CD4 + SP T cells, CD8 + SP T cells, αβ T cells and γδ T cells decreased significantly on the first day after irradiation. NK cells and NKT cells did not change significantly after irradiation. The above results indicate that the changes in lymphocytes have a direct relationship to radiosensitivity, and the origin and distribution in lymphocyte subsets. (author)

  14. Changes in lymphocyte subsets due to local irradiation of a portion of the maxilla in mice. A study of minor population lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Chiho; Satoh, Daigo; Yosue, Takashi [Nippon Dental Univ., Tokyo (Japan). School of Dentistry

    2001-03-01

    In the present study we investigates the influence of the local irradiation of a portion of the maxilla on the numbers of lymphocyte subsets in peripheral blood and spleen, specifically minor population lymphocytes ({gamma}{delta}T cells and NKT cells). Male C57BL/6 mice at 15 weeks of age were used for the experiments. In the irradiation group, a portion of the maxilla was exposed to X-ray (2.0 Gy/min, 10 Gy) and we analyzed lymphocytes using flow cytometry (anti-CD3, CD4, CD8, TCR{alpha}{beta}, TCR{gamma}{delta} and NK1.1 monoclonal antibodies), and compared the outcome to that obtained from the non-irradiation groups. The following results were obtained: In peripheral blood, CD4{sup +}SP T cells, CD8{sup +}SP T cells, {alpha}{beta} T cells, {gamma}{delta} T cells and NK cells decreased significantly on the first day and third day after irradiation. NKT cells decreased significantly on the third day after irradiation. In spleen, CD4{sup +}SP T cells, CD8{sup +}SP T cells, {alpha}{beta} T cells and {gamma}{delta} T cells decreased significantly on the first day after irradiation. NK cells and NKT cells did not change significantly after irradiation. The above results indicate that the changes in lymphocytes have a direct relationship to radiosensitivity, and the origin and distribution in lymphocyte subsets. (author)

  15. 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.

  16. 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.

  17. Reference range for T lymphocytes populations in blood donors from two different regions in Brazil

    Directory of Open Access Journals (Sweden)

    A.J.L. Torres

    Full Text Available This study defined the normal variation range for different subsets of T-lymphocyte cells count in two different Brazilian regions. We analysed the T-lymphocytes subpopulations (CD3+, CD4+, CD8+ in blood donors of two Brazilian cities, located in North (Belem, capital state of Para, indian background and Northeast (Salvador, capital state od Bahia, African background regions of Brazil. Results were compared according to gender, stress level (sleep time lower than 8 hours/day, smoking, and alcohol intake. Lymphocytes subpopulations were measured by flow cytometry. Five hundred twenty-six blood donors from two Brazilians cities participated in the study: 450 samples from Bahia and 76 samples from Pará. Most (60% were men, 59% reported alcohol intake, 12% were smokers, and 80% slept at least 8 h/day. Donors from Bahia presented with significantly higher counts for all parameters, compared with Para. Women had higher lymphocytes levels, in both states, but only CD4+ cells count was significantly higher than men's values. Smokers had higher CD4+ counts, but sleep time had effect on lymphocytes levels only for Para's donors (higher CD3+ and CD4+ counts. That state had also, a higher proportion of donors reporting sleep time <8 h/day. The values for CD3, CD4 and CD8+ cells count were significantly higher in blood donors from Bahia than among those from Pará. Female gender, alcohol intake, stress level, and smoking were associated with higher lymphocyte counts. The use of a single reference range for normal lymphocytes count is not appropriate for a country with such diversity, like Brazil is.

  18. Usefulness of Eosinophil-Lymphocyte Ratio to Predict Stent Restenosis

    Directory of Open Access Journals (Sweden)

    Mehmet Zihni Bilik

    2016-06-01

    Full Text Available Objective: Stent restenosis (SR is an important compli­cation of percutaneous coronary intervention. There are many studies explored the relation of eosinophils with SR, however, there is no data about relationship between eo­sinophil-lymphocyte ratio (ELR and SR. In this study we aimed to investigate the relationship between the value of ELR on admission and SR. Methods: The study was included 314 patients who had been applied a coronary stent implantation and they were admitted to cardiology clinic with stabile angina and un­derwent repeat coronary angiography. The data obtained from patients were analyzed retrospectively. The patient group was consisted of 197 patients who were diagnosed as SR, and the control group was consisted of 117 pa­tients whose stents were patent angiographically. Results: The groups were similar in terms of age, gender, hypertension, diabetes mellitus, LDL-C, HDL-C, platelet count, platelet-lymphocyte ratio (PLR, hemoglobin and left ventricle ejection fraction (LVEF. White blood cell (WBC, neutrophil, eosinophil, C-reactive protein (CRP, ELR and neutrophil-lymphocyte ratio (NLR on admission were higher in the SR group compared to the controls. All patients were categorized into two groups according to ELR values and SR was more frequent in the high ELR group compared to low ELR group. An ELR value of ≥0.745 predicted SR with 64% sensitivity and 61% specif­ity. Conclusion: In this study ELR was found statistically higher in SR patients compared to the controls. Accord­ing to our data ELR as an inexpensive and easy method, may contribute to determination of high risk patients and increased ELR can be used as a predictor of SR.

  19. 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.

  20. 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.

  1. Radioiodine-induced changes in lymphocyte subsets in patients with differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tofani, A.; Sciuto, R.; Cioffi, R.P.; Pasqualoni, R.; Rea, S.; Festa, A.; Maini, C.L. [Department of Nuclear Medicine, Regina Elena Cancer Institute, Rome (Italy); Gandolfo, G.M.; Arista, M.C. [Department of Clinical Pathology, Regina Elena Cancer Institute, Rome (Italy)

    1999-08-01

    This study evaluated changes in lymphocyte subsets in patients with thyroid carcinoma who received iodine-131 for diagnostic and therapeutic purposes. Twenty thyroid cancer patients were entered in the study after total thyroidectomy: ten patients (group A) underwent whole-body scintigraphy with 185 MBq of {sup 131}I and the other ten (group B) received 3700 MBq of {sup 131}I therapy. All patients were in a hypothyroid state at the time of administration of {sup 131}I and started l-thyroxine 150 {mu}g/day 3 days after {sup 131}I administration. Free and bound triiodothyronine and thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, thyroid peroxidase/microsomal antibodies, white blood cell, lymphocyte counts and lymphocyte subsets were serially determined at baseline and at days 2, 7, 15, 30 and 60 after {sup 131}I administration. Twenty healthy age- and sex-matched individuals were used as a reference population for lymphocyte subset values. In group A only a reduction in NK cells at days 7 (P=0.043) and 15 (P=0.037) was observed. In group B, patients showed a delayed reduction in the total lymphocyte count at days 15, 30 and 60 (P=0.008, 0.004 and 0.018, respectively), and a decrease in B cells throughout the study (at days 7, 15, 30 and 60: P=0.006, 0.0017, 0.0017 and 0.0017 respectively). A transient decrease in NK cells was observed at days 15 (P=0.025) and 30 (P=0.008). Among T cells, the helper phenotype (CD4+) was mainly affected, resulting in a reduction in the CD4+/CD8+ ratio at day 60 (P=0.046). Comparing the two groups, the numbers of B lymphocytes at day 30 (P=0.023) and NK cells at days 2 (P=0.037) and 30 (P=0.023) were significantly lower in group B. Neither group showed any clinical sign of immunosuppression during the follow-up period. In patients with thyroid cancer the sensitivity of lymphocytes to the effects of {sup 131}I administered for diagnostic or therapeutic purposes depends upon lymphocyte phenotype and {sup

  2. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    Science.gov (United States)

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  3. In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes

    Directory of Open Access Journals (Sweden)

    Pushpa Ruwali

    2018-01-01

    Full Text Available Aim: Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD in chicken lymphocytes. Materials and Methods: Fresh aerial parts of A. indica Willd. (family: Asteraceae specimens were collected (altitude 1560 m, gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME. Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 107 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS and concanavalin A (Con A, respectively. Results: Maximum concentration of AME exhibiting 100% cell viability (MNCD was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 μg/ml dose of AME, resulted in significant (p<0.05 upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS and a significant (p<0.05 increase of 12.018% T cells proliferation in the presence of the mitogen (Con A, as compared to the control. Conclusion: The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

  4. Flow Cytometry Study of Lymphocyte Subsets in Malnourished and Well-Nourished Children with Bacterial Infections

    Science.gov (United States)

    Nájera, Oralia; González, Cristina; Toledo, Guadalupe; López, Laura; Ortiz, Rocío

    2004-01-01

    Protein-energy malnutrition is the primary cause of immune deficiency in children across the world. It has been related to changes in peripheral T-lymphocyte subsets. The aim of the present study was to evaluate the effects of infection and malnutrition on the proportion of peripheral-lymphocyte subsets in well-nourished non-bacterium-infected (WN), well-nourished bacterium-infected (WNI), and malnourished bacterium-infected (MNI) children by flow cytometry. A prospectively monitored cohort of 15 MNI, 12 WNI, and 17 WN children was studied. All the children were 3 years old or younger and had only bacterial infections. Results showed a significant decrease in the proportion of T CD3+ (P < 0.05 for relative and P < 0.03 for absolute values), CD4+ (P < 0.01 for relative and absolute values), and CD8+ (P < 0.05 for relative values) lymphocyte subsets in WNI children compared to the results seen with WN children. Additionally, B lymphocytes in MNI children showed significant lower values (CD20+ P < 0.02 for relative and P < 0.05 for absolute values) in relation to the results seen with WNI children. These results suggest that the decreased proportions of T-lymphocyte subsets observed in WNI children were associated with infection diseases and that the incapacity to increase the proportion of B lymphocyte was associated with malnutrition. This low proportion of B lymphocytes may be associated with the mechanisms involved in the immunodeficiency of malnourished children. PMID:15138185

  5. In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes.

    Science.gov (United States)

    Ruwali, Pushpa; Ambwani, Tanuj Kumar; Gautam, Pankaj

    2018-01-01

    Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells) proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD) in chicken lymphocytes. Fresh aerial parts of A. indica Willd. (family: Asteraceae) specimens were collected (altitude 1560 m), gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME). Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 10 7 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Maximum concentration of AME exhibiting 100% cell viability (MNCD) was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 µg/ml dose of AME, resulted in significant (p<0.05) upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS) and a significant (p<0.05) increase of 12.018% T cells proliferation in the presence of the mitogen (Con A), as compared to the control. The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

  6. 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.

  7. 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., ...

  8. 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.

  9. 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.

  10. 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.

  11. 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 ...

  12. 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...

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

    International Nuclear Information System (INIS)

    Lohmann, Tania Helena Ochi.

    1995-01-01

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

  14. 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

  15. Use of the lymphocyte count as a diagnostic screen in adults with suspected Epstein-Barr virus infectious mononucleosis.

    Science.gov (United States)

    Biggs, Timothy C; Hayes, Stephen M; Bird, Jonathan H; Harries, Philip G; Salib, Rami J

    2013-10-01

    To evaluate the predictive diagnostic accuracy of the lymphocyte count in Epstein-Barr virus-related infectious mononucleosis (IM). Retrospective case note and blood results review within a university-affiliated teaching hospital. A retrospective review of 726 patients undergoing full blood count and Monospot testing was undertaken. Monospot testing outcomes were compared with the lymphocyte count, examining for significant statistical correlations. With a lymphocyte count of ≤4 × 10(9) /L, 99% of patients had an associated negative Monospot result (sensitivity of 84% and specificity of 94%). A group subanalysis of the population older than 18 years with a lymphocyte count ≤4 × 10(9) /L revealed that 100% were Monospot negative (sensitivity of 100% and specificity of 97%). A lymphocyte count of ≤4 × 10(9) /L correlated significantly with a negative Monospot result. A lymphocyte count of ≤4 × 10(9) /L appears to be a highly reliable predictor of a negative Monospot result, particularly in the population aged >18 years. Pediatric patients, and adults with strongly suggestive symptoms and signs of IM, should still undergo Monospot testing. However, in adults with more subtle symptoms and signs, representing the vast majority, Monospot testing should be restricted to those with a lymphocyte count >4 × 10(9) /L. NA Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  16. 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.)

  17. Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques

    Directory of Open Access Journals (Sweden)

    Saraswathy Radha

    2000-01-01

    Full Text Available Blood lymphocytes from xeroderma pigmentosum (XP and Fanconi anemia (FA patients were assessed for their sensitivity to ionizing radiation by estimating the frequency of X-ray (1 and 2 Gy-induced chromosome aberrations (CA. The frequencies of aberrations in the whole genome were estimated in Giemsa-stained preparations of lymphocytes irradiated at G0 or G2 stages. The frequencies of translocations and dicentrics involving chromosomes 1 and 3 as well as the X-chromosome were determined in slides stained by fluorescence in situ hybridization (FISH technique. An increase in all types of CA was observed in XP and FA lymphocytes irradiated at G0 when compared to controls. The frequency of dicentrics and rings was 6 to 27% higher (at 1 and 2 Gy in XP lymphocytes and 37% higher (at 2 Gy in FA lymphocytes than in controls, while chromosome deletions were higher in irradiated (30% in 1 Gy and 72% in 2 Gy than in control XP lymphocytes and 28 to 102% higher in FA lymphocytes. In G2-irradiated lymphocytes the frequency of CA was 24 to 55% higher in XP lymphocytes than in controls. In most cases the translocation frequencies were higher than the frequencies of dicentrics (21/19.

  18. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial.

    Science.gov (United States)

    O'Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

    2014-01-01

    Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one

  19. 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

  20. Assessment of DNA damage in blood lymphocytes of bakery workers by comet assay.

    Science.gov (United States)

    Kianmehr, Mojtaba; Hajavi, Jafar; Gazeri, Javad

    2017-09-01

    The comet assay is widely used in screening and identification of genotoxic effects of different substances on people in either their working or living environment. Exposure to fuel smoke leads to DNA damage and ultimately different types of cancer. Using a comet assay, the present study aimed to assess peripheral blood lymphocyte DNA damage in people working in bakeries using natural gas, kerosene, diesel, or firewood for fuel compared to those in the control group. The subjects of this study were 55 people in total who were divided into four experimental groups, each of which comprised of 11 members (based on the type of fuel used), and one control group comprised of 11 members. Using CometScore, the subjects' peripheral blood lymphocytes were examined for DNA damage. All bakers, that is, experimental subjects, showed significantly greater peripheral blood lymphocyte DNA damage compared to the individuals in the control group. There was greater peripheral blood lymphocyte DNA damage in bakers who had been using firewood for fuel compared to those using other types of fuel to such an extent that tail moments (µm) for firewood-burning bakers was 4.40 ± 1.98 versus 1.35 ± 0.84 for natural gas, 1.85 ± 1.33 for diesel, and 2.19 ± 2.20 for kerosene. The results indicated that burning firewood is the greatest inducer of peripheral blood lymphocytes DNA damage in bakers. Nonetheless, there was no significant difference in peripheral blood lymphocyte DNA damage among diesel and kerosene burning bakers.

  1. Investigation of neutrophil-to-lymphocyte ratio and mean platelet volume in sudden hearing loss,

    Directory of Open Access Journals (Sweden)

    Rauf Oguzhan Kum

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Several theories attempt to explain the pathophysiology of sudden hearing loss. OBJECTIVE: The objective of this study was to investigate the possible role of inflammation and atherothrombosis in sudden hearing loss patients through the neutrophil-to-lymphocyte ratio and mean platelet volume. METHODS: Study design - retrospective cross-sectional historical cohort. This study was conducted on two groups: one with 59 individuals diagnosed with sudden hearing loss, and other with 59 healthy individuals with the same characteristics of gender and age distribution, neutrophil-to-lymphocyte ratio and mean platelet volume levels were measured in patients diagnosed with sudden hearing loss as well as in the control group, and it was verified whether these results interfered for a better or worse prognosis with treatment of sudden deafness. RESULTS: Neutrophil-to-lymphocyte ratio levels are much higher in patients diagnosed with sudden hearing loss compared to the control group. Similarly, mean levels of neutrophil-to-lymphocyte ratio are higher in non-recovered versus recovered patients (p = 0.001. However, we could not find a correlation with mean platelet volume levels (p > 0.05. CONCLUSION: Neutrophil-to-lymphocyte ratio is a quick and reliable indicator regarding diagnosis and prognosis of sudden hearing loss; on the other hand, mean platelet volume may be considered a less important indicator in this aspect.

  2. Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology

    Directory of Open Access Journals (Sweden)

    MARISOL HERRERA-RIVERO

    2013-01-01

    Full Text Available Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

  3. Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes

    Directory of Open Access Journals (Sweden)

    Somayeh Shahani

    2015-04-01

    Full Text Available The radioprotective effect of Achillea millefolium L (ACM extract was investigated against genotoxicity induced by ionizing radiation (IR in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.

  4. Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes

    International Nuclear Information System (INIS)

    Abramovsky-Kaplan, I.; Jones, I.S.

    1984-01-01

    Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit increased spontaneous fragility. X-irradiation (25-200 rad) did not significantly increase SCE in unilateral retinoblastoma lymphocytes when compared with controls (P greater than 0.50). However, bilaterally affected subjects and three unaffected relatives demonstrated a statistically significant increase in SCE (P less than 0.01). In conclusion, hereditary retinoblastoma lymphocytes appear more radiosensitive than sporadic retinoblastoma, perhaps, reflecting the increased second malignancies in germinal mutation retinoblastoma. In addition, the analysis of radiation-induced SCE in peripheral blood lymphocytes of RB patients and family members may provide a valuable tool increasing the accuracy of genetic counseling for this disorder. Additional studies of RB patients and families are needed to assess the relevance of this approach to genetic counseling

  5. The effect of varying incubation times for hypotonic treatment of lymphocytes in dicentric assay technique

    International Nuclear Information System (INIS)

    Noraisyah Yusof; Noriah Jamal; Rahimah Abdul Rahim; Juliana Mahamad Napiah

    2010-01-01

    The International Atomic Energy Agency (IAEA) has recommended that incubation time for the hypotonic treatment of lymphocytes in dicentric assay technique to be between 15 to 20 minutes. Incubation time will effect the hypotonic treatment of lymphocytes and thus, the breakage of cytoplasmic membrane. The objective of this study is to examine the effect of varying incubation times for hypotonic treatment of lymphocytes in dicentric assay technique. In this study, we choose to use our standard protocol for dicentric assay technique. However, for the hypotonic treatment of lymphocytes, the incubation times were varied from 10, 15, 20, 25 and 30 minutes respectively. Lymphocytes were then fixed and stained with Giemsa. The cells were then analyzed for clear background that indicates good metaphases. We found that incubation time of 30 minutes gives the best metaphase images. This incubation time is longer than what has been recommended by the IAEA. This maybe explained by the fact that our country's climate is of higher humidity compared with the European countries. (author)

  6. FEATURES OF METABOLIC INDEXES OF BLOOD LYMPHOCYTES IN THE PATIENTS WITH EPIDURAL FIBROSIS FOLLOWING LUMBAR MICRODISCECTOMY

    Directory of Open Access Journals (Sweden)

    N. V. Isaeva

    2008-01-01

    Full Text Available Abstract. A complex immunologic examination of fifty patients with clinically significant postoperative fibrosis has been performed. Immunogram indexes were determined, and activities of basic oxidation-reduction enzymes were investigated in blood lymphocytes. What concerned immune status of the patients under study, some peculiar features have been revealed, with respect to cellular and humoral compartments, i.e., relative increase in CD3+ population, a shift to CD4+ cells in the ratio of lymphocyte subpopulations, higher indexes of immune regulation and phagocytosis, increased IgG level, and lower content of IgA, as compared to appropriate controls. Metabolic parameters of lymphocytes reflect their functional activation, being expressed as an enhanced ability for intracellular synthetic processes, elevated functional activity of lymphocytes, and increased immune response. The general pattern of changes in immune status and metabolic indexes of lymphocytes allow us to assume participation of autoimmune component in progression of epidural fibrosis. The data obtained may be used in combined diagnostics and correction of this disorder. (Med. Immunol., vol. 10, N 6, pp 589-592.

  7. Intracellular calcium mobilization in human lymphocytes in the presence of synthetic IgG Fc peptides

    International Nuclear Information System (INIS)

    Plummer, J.M.; Panahi, Y.P.; McClurg, M.R.; Hahn, G.S.; Naemura, J.R.

    1986-01-01

    Certain synthetic peptides derived from the Fc region of human IgG can suppress the mixed lymphocyte response. These peptides were tested for the ability to induce intracellular calcium mobilization in human lymphocytes using fura-2/calcium fluorescence. T cells were isolated by rosetting and were > 90% OKT3 positive. Lymphocytes were incubated with the acetoxymethyl ester of fura-2 (10 μM) for 60 minutes at 37 0 C. Fluorescence intensity changes at 505 nm were monitored at an excitation lambda of 340 nm. Fura-2 was not cytotoxic compared to quin-2 since fura-2 loaded mononuclear cells incorporated 3 H-thymidine when stimulated by PHA, succinyl Con A, PWM or LPS-STM whereas quin-2 loaded cells showed a dose dependent inhibition of proliferation. Those synthetic peptides (5 to 400 μg/ml) that suppressed the MLR induced a dose dependent increase in intracellular calcium in mononuclear cells, lymphocytes, non-T cells and T cells. The fura-2 calcium fluorescence time course response was similar for peptide, PHA and succinyl Con A. These results suggest that these immunoregulatory peptides suppress 3 H-thymidine incorporation at a point after intracellular calcium mobilization and that fura-2 has advantages over quin-2 in measuring intracellular calcium levels in lymphocytes

  8. Sandwich radioimmunolabeling for the study of surface properties of bone marrow lymphocytes

    International Nuclear Information System (INIS)

    Yoshida, Y.; Uchino, H.; Kuribayashi, K.; Shimizu, S.; Konda, S.

    1980-01-01

    A modification of sandwich radioautographic method was applied to the study of surface immunoglobulin and/or specific antigens on small lymphocytes in mouse and human bone marrow. After incubation of marrow cell suspensions at 37 0 C, cells were reacted at 0 0 C for 30 min with graded dilutions of rabbit anti-mouse or anti-human immunoglobulin followed by further reaction with a sheep anti-rabbit immunoglobulin labeled with 125 I. Detectable surface immunoglobulin was demonstrated in approximately one-third of mouse marrow lymphocytes and 20-25% of human marrow lymphocytes. The densities of surface immunoglobulin as assessed by grain counts on individual labeled lymphocytes tended to be lower in the marrow than in spleen or peripheral blood. When the same rabbit antiserum was used to compare the sensitivity of the sandwich method with that of the direct radioautography, the former was found sufficiently sensitive to give a plateau level of labeling without seriously increasing background grains. The advantages of the method are discussed with reference to studies on T and B cell specific antigens on human bone marrow lymphocytes. (Auth.)

  9. Manifestation of radiaton injury of human lymphocytes using PHA mitogenic stimulation in different culture systems

    International Nuclear Information System (INIS)

    Horky, J.

    1986-01-01

    The proliferative response of human lymphocytes to phytohemagglutinin in vitro is affected by X-irradiation. Dose-related changes in mitogenic stimulation of irradiated lymphocytes were compared for two culture systems - the cultivation of separated lymphocytes and the cultivation of whole blood. In the whole blood cultures, the proliferative activity of stimulated lyphocytes was markedly and reproducibly depressed by irradiation. An exponential curve could be fitted to the values of mitogenic response within a dose range from 0 to 2.5 Gy with high correlation. In a modified test where the mitogenic stimulus was given after a 24 h delay, depression in the response was even more pronounced. Radiosensitivity of human lymphocytes as determined by means of mitogenic stimulation in the whole blood cultures appears to be a characteristic individual feature. The mean D 37 value of the radiation-induced depression in mitogenic response in a group of 20 healthy donors was 2.5 Gy in the standard test and 2.0 Gy in the test with a delayed mitogenic stimulus. In contrast, the data obtained from separated lymphocyte cultures were characterized by a high degree of test-to-test variability and by much lower radiosensitivity. The possible mechanisms of these distinctive manifestations of the same primary radiation injury are discussed. (author) 3 tabs., 2 figs., 12 refs

  10. The effects of 3-methylcholanthrene on lymphocyte proliferation in the common carp (Cyprinus carpio L.)

    International Nuclear Information System (INIS)

    Reynaud, S.; Deschaux, P.

    2005-01-01

    The sensitivity of lymphocyte proliferation as bioindicator of pollution stress was evaluated in the common carp (Cyrinus carpio L.). The time course response of peripheral blood leukocyte proliferation in response or not to mitogens was measured from 1 to 7 days after peritoneal injection of 3-methylcholantrene (3-MC), and compared to the time course response of a highly sensitive biomarker, induction of cytochrome P450. 3-Methylcholanthrene (40 mg kg -1 ) inhibited both B- and T-lymphocyte proliferation in response to lipopolysaccharide (LPS) and concanavalin A (Con A). Studies with α-naphtofiavone, suggest the lack of metabolic processes. 3-Methylcholanthrene alone strongly stimulated resting peripheral blood leukocytes (PBLs) proliferation. This effect was not transient. The induction of lymphocyte proliferation paralleled the increase in cytochrome P450 content in the liver. The specificity of polycyclic aromatic hydrocarbon (PAH)-induced lymphocyte proliferation suggests that this immune activity may be an early marker of exposure to PAHs in aquatic environments. The capacity of 3-MC to induce rapid lymphocyte proliferation may be related to PAH-induced rapid clonal expansion in mammals. These results strongly suggested that the underlying mechanism might be the same in both models. More studies are needed in fish to explain this phenomenon and may be helpful in understanding the occurrence of neoplastic epizootics in fish associated with PAH exposition

  11. Efficient clinical-scale enrichment of lymphocytes for use in adoptive immunotherapy using a modified counterflow centrifugal elutriation program.

    Science.gov (United States)

    Powell, Daniel J; Brennan, Andrea L; Zheng, Zhaohui; Huynh, Hong; Cotte, Julio; Levine, Bruce L

    2009-01-01

    Clinical-scale lymphocyte enrichment from a leukapheresis product has been performed most routinely using costly magnetic bead separation systems that deplete monocytes, but this procedure may leave behind residual beads or antibodies in the enriched cell product. Counterflow centrifugal elutriation has been demonstrated previously to enrich monocytes efficiently for generation of dendritic cells. This study describes a modified elutriation procedure for efficient bead-free economical enrichment of lymphocytes from leukapheresis products from healthy donors and study subjects with human immunodeficiency virus (HIV) infection or malignancy. Modified program settings and conditions for the CaridianBCT Elutra device were investigated to optimize lymphocyte enrichment and recovery. Lymphocyte enrichment was measured using a novel approach utilizing cell sizing analysis on a Beckman Coulter Multisizer and confirmed by flow cytometry phenotypic analysis. Efficient enrichment and recovery of lymphocytes from leukapheresis cell products was achieved using modified elutriation settings for flow rate and fraction volume. Elutriation allowed for enrichment of larger numbers of lymphocytes compared with depletion of monocytes by bead adherence, with a trend toward increased lymphocyte purity and yield via elutriation, resulting in a substantial reduction in the cost of enrichment per cell. Importantly, significant lymphocyte enrichment could be accomplished using leukapheresis samples from healthy donors (n=12) or from study subjects with HIV infection (n=15) or malignancy (n=12). Clinical-scale closed-system elutriation can be performed efficiently for the selective enrichment of lymphocytes for immunotherapy protocols. This represents an improvement in cost, yield and purity over current methods that require the addition of monocyte-depleting beads.

  12. Lymphocyte ceruloplasmin and Behçet's disease.

    Science.gov (United States)

    Oliveira, Rita; Banha, João; Martins, Fátima; Paixão, Eleonora; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Costa, Luciana

    2006-01-01

    Behçet's disease (BD) is a rare chronic inflammatory disorder of unknown aetiology. However, it has been postulated that a dysregulation of the prooxidant/antioxidant balance may be important to its pathogenesis. Ceruloplasmin (CP) is an acute phase protein expressed at the surface of peripheral blood lymphocytes (PBL) with antioxidant properties and with a relevant role in iron (Fe) metabolism. To study CP expression at the surface of PBL (PBLCP) in patients with BD. We measured serum CP and PBLCP obtained from BD patients (n=10) and respective controls (n=10) using nephelometry and flow cytometry techniques, respectively. Additionally, haematological parameters, biochemical Fe metabolism markers [serum Fe, serum ferritin, serum transferrin, total Fe binding capacity (TIBC), transferrin saturation] and non-specific markers of inflammation [serum C reactive protein (CRP), beta2-microglobulin] were measured in all individuals. Despite the absence of significant differences between the two study groups when comparing serum CP, a significant difference in PBLCP was found in BD patients mainly due to a significant decrease of CP expression at the surface of CD3-CD56+ lymphocytes. Also, a significant decrease of PBLCP was observed in patients treated with azathioprine compared to patients that were not being treated with this drug. According to this study, we suggest that the significant decrease of PBLCP observed in BD patients might be due to azathioprine treatment and not directly related to the pathophysiology of BD.

  13. Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

    Science.gov (United States)

    Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

    2011-04-01

    Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Caporossi, D.; Sebastiani, G.; Nicoletti, B. (Rome 2 University (Italy). Department of Public Health and Cellular Biology); Masala, C. (' La Sapienza' University, rome (Italy). Institute of Infectious and Tropical Diseases)

    1990-03-01

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  16. Comparison of HPRT mutant frequency in human peripheral blood lymphocytes of smokers and non-smokers

    International Nuclear Information System (INIS)

    Vivek Kumar, P.R.; Mary Mohankumar, N.; Chatterjee, Indranil; Jeevanram, R.K.

    2003-01-01

    The mutant frequency of hypoxanthine guanine phospho ribosyl transferase (HPRT) has been studied in peripheral blood lymphocytes of six non-smokers and six smokers. The mutant frequency was studied by following a Uniform Operating Protocol (UOP). The mean lymphocyte cloning efficiency of non-smokers and smokers was about 31 %. The mean mutant frequency obtained in smokers showed a marginal increase compared to that of non-smokers, but they were not significantly different (P= 0.1416). This paper discusses the methodology adopted and the results obtained with the preliminary finding. (author)

  17. Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    International Nuclear Information System (INIS)

    AlSuhaibani, E.S

    2008-01-01

    The present work is aimed at evaluating the radioprotective effect of curcumin on γ radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 γg/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against γ-radiation induced chromosome aberration at certain doses. (author)

  18. Changes in the Structure of the Chromosomes of Lymphocytes during Persistent Infection in Children

    Directory of Open Access Journals (Sweden)

    V. S. Sevryukova

    2016-01-01

    Full Text Available Children with chronic diseases of respiratory tract were investigated for IgM and IgG serum antibodies to viruses (Herpes simplex virus, Epstein-Barr virus, Cytomegalovirus and bacteria (Chlamydia trachomatis + pneumoniae, Mycoplasma pneumonia by ELISA and for telomere length of their lymphocytes by fluorescent hybridization in situ followed by flow cytomerty (FlowFISH. The purpose of the study was to compare the lymphocyte telomere length of these seropositive and seronegative children. Regression analysis and analysis of percent distribution relative to the regression line have compensated age differences between seropositive and seronegative groops and demonstrated shorter telomeres in lymphocytes of children those have serum antibodies to viruses in all combinations (including combinations with antibodies to bacteria in contrast to seronegative children of the same age.

  19. 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.

  20. 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.

  1. The Relationship Between 14C Urea Breath Test Results and Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios

    Directory of Open Access Journals (Sweden)

    Ertan Şahin

    2018-04-01

    Full Text Available Aim: Neutrophil/lymphocyte ratio (NLR and platelet/lymphocyte ratio (PLR are used as inflammatory markers in several diseases. However, there are little data regarding the diagnostic ability of NLR and PLR in Helicobacter pylori. We aimed to assess the association between the 14C urea breath test (14C-UBT results and NLR and PLR in H. pylori diagnosis. Methods: Results of 89 patients were retrospectively analysed in this study. According to the 14C-UBT results, patients were divided into two groups: H. pylori (+ and H. pylori (- (control group. Haematological parameters, including hemoglobine, white blood cell (WBC count, neutrophil count, lymphocyte count, NLR, platelet count, and PLR were compared between the two groups. Results: The mean total WBC count, neutrophil count, NLR and PLR in H. pylori (+ patients were significantly higher than in the control group (p<0.001 for all these parameters. In the receiver operating characteristic curve analysis, the cut-off value for NLR and PLR for the presence of H. pylori was calculated as ≥2.39 [sensitivity: 67.3%, specificity: 79.4%, area under the curve (AUC: 0.747 (0.637-0.856, p<0.0001] and ≥133.3 [sensitivity: 61.8%, specificity: 55.9%, AUC: 0.572 (0.447-0.697, p<0.05], respectively. Conclusion: The present study shows that NLR and PLR are associated with H. pylori positivity based on 14C-UBT, and they can be used as an additional biomarker for supporting the 14C-UBT results.

  2. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Burger, Jan A; Tedeschi, Alessandra; Barr, Paul M; Robak, Tadeusz; Owen, Carolyn; Ghia, Paolo; Bairey, Osnat; Hillmen, Peter; Bartlett, Nancy L; Li, Jianyong; Simpson, David; Grosicki, Sebastian; Devereux, Stephen; McCarthy, Helen; Coutre, Steven; Quach, Hang; Gaidano, Gianluca; Maslyak, Zvenyslava; Stevens, Don A; Janssens, Ann; Offner, Fritz; Mayer, Jiří; O'Dwyer, Michael; Hellmann, Andrzej; Schuh, Anna; Siddiqi, Tanya; Polliack, Aaron; Tam, Constantine S; Suri, Deepali; Cheng, Mei; Clow, Fong; Styles, Lori; James, Danelle F; Kipps, Thomas J

    2015-12-17

    Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; PIbrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, Pibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall

  3. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, A. [Institute of Nuclear Physics, Cracow (Poland)

    1997-12-31

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  4. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1997-01-01

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  5. Elevated neutrophil-lymphocyte ratio in patients with euthyroid chronic autoimmune thyreotidis

    Directory of Open Access Journals (Sweden)

    Keskin Havva

    2016-07-01

    Full Text Available Objective. The neutrophil-lymphocyte ratio (NLR, determined from peripheral blood, is accepted as an available and practical indicator of the systemic inflammation. In this study, we aimed to determine whether the NLR was higher in euthyroid chronic autoimmune thyreotidis (CAT patients compared to a healthy control group.

  6. The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer

    DEFF Research Database (Denmark)

    Baranyai, Zsolt; Krzystanek, Marcin; Josa, Valeria

    2014-01-01

    The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathologi...

  7. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    International Nuclear Information System (INIS)

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-01-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed

  8. Lymphocytes contribute to biliary injury and fibrosis in experimental xenobiotic-induced cholestasis

    International Nuclear Information System (INIS)

    Joshi, Nikita; Kopec, Anna K.; Cline-Fedewa, Holly; Luyendyk, James P.

    2017-01-01

    The etiology of chronic bile duct injury and fibrosis in patients with autoimmune cholestatic liver diseases is complex, and likely involves immune cells such as lymphocytes. However, most models of biliary fibrosis are not autoimmune in nature. Biliary fibrosis can be induced experimentally by prolonged exposure of mice to the bile duct toxicant alpha-naphthylisothiocyanate (ANIT). We determined whether lymphocytes contributed to ANIT-mediated biliary hyperplasia and fibrosis in mice. Hepatic accumulation of T-lymphocytes and increased serum levels of anti-nuclear-autoantibodies were evident in wild-type mice exposed to ANIT (0.05% ANIT in chow). This occurred alongside bile duct hyperplasia and biliary fibrosis. To assess the role of lymphocytes in ANIT-induced biliary fibrosis, we utilized RAG1 −/− mice, which lack T- and B-lymphocytes. ANIT-induced bile duct injury, indicated by increased serum alkaline phosphatase activity, was reduced in ANIT-exposed RAG1 −/− mice compared to ANIT-exposed wild-type mice. Despite this reduction in biliary injury, ANIT-induced bile duct hyperplasia was similar in wild-type and RAG1 −/− mice. However, hepatic induction of profibrogenic genes including COL1A1, ITGβ6 and TGFβ2 was markedly attenuated in ANIT-exposed RAG1 −/− mice compared to ANIT-exposed wild-type mice. Peribiliary collagen deposition was also reduced in ANIT-exposed RAG1 −/− mice. The results indicate that lymphocytes exacerbate bile duct injury and fibrosis in ANIT-exposed mice without impacting bile duct hyperplasia.

  9. Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases

    International Nuclear Information System (INIS)

    Cadman, E.C.; Capizzi, R.L.; Bertino, J.R.

    1977-01-01

    The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p < 0.0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were threated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival

  10. Listeria monocytogenes Infection in Hairy Cell Leukemia: A Case Report and Literature Review

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    James C. Barton

    2018-01-01

    Full Text Available Listeria monocytogenes infections have been described in patients with diverse types of malignancy, especially leukemia. We report the case of a 65-year-old man with previously untreated hairy cell leukemia characterized by CD5 positivity and trisomy 12 (3% of blood lymphocytes who developed bacteremia due to L. monocytogenes serotype 1/2b. We summarize clinical features and treatment of this patient and five previously reported patients with hairy cell leukemia who also had L. monocytogenes infections. All six patients were men. Their mean age at infection diagnosis was 70 y. Three men had undergone splenectomy 4–11 y before they developed L. monocytogenes infection. The central nervous system was the primary site of infection in four men. Bacteremia alone occurred in two other men. At diagnosis of infection, one man was receiving antileukemia chemotherapy and another man was receiving treatment for Kaposi’s sarcoma. Two other patients had other comorbid conditions. All six men recovered from their infections.

  11. Characteristics of T lymphocyte subpopulations 

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    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. 

  12. Biological Prognostic Markers in Chronic Lymphocytic Leukemia

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    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.

  13. 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)

  14. REACTIVITY OF BLOOD LYMPHOCYTES IN PULMONARY TUBERCULOSIS

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    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.

  15. 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

  16. 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)

  17. Lymphocytic hypophysitis masquerading as pituitary adenoma

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    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.

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

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    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

  19. Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines

    International Nuclear Information System (INIS)

    Merk, Hans F.

    2005-01-01

    For all types of allergic reactions including immediate type of reactions, types II and III reactions as well as delayed-type reactions the recognition of the antigen by specifically sensitized T-lymphocytes is a prerequisite. Evidences for the key role of T-lymphocytes in the pathophysiology of allergic drug reactions are positive patch test reactions and the LTT. The proliferative response that can be measured by means of the incorporation of 3H-thymidine during DNA synthesis can be expressed as stimulation index (SI) which is the relation between the cell proliferation with antigen compared without antigen. In addition drug-specific activation of PBMC consistently resulted in IL-5 expression and secretion. The sensitivity of the LTT for the detection of drug sensitization could be improved up to 92% by the measurement of released interleukin-5. The expression and secretion of other cytokines such as IFN-γ and IL-10 was less consistently and had a diagnostic sensitivity of 36 and 50%, respectively. Microarrays are a promising new technical platform to look for better markers which can be used as a read out in the LTT and other similar assays and to study pharmacological interactions between drugs including cytokines such as interferons and the immune system

  20. The Effect of Cardiac Surgery on Peripheral Blood Lymphocyte Populations

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    Karolína Jankovičová

    2008-01-01

    Full Text Available Background: Cardiac surgery using cardiopulmonary bypass (CPB is associated with some adverse postoperative complications caused by an altered immune response. An alternative approach to cardiac surgery, operating without the use of CPB (i.e. off-pump surgery, seems to display less adverse impacts on the immune response. Patients and Methods: Peripheral blood lymphocytes in 40 patients undergoing cardiac surgery either with CPB (“on-pump” or without CPB (“off-pump” were followed using flow cytometry. The samples of peripheral blood were taken at five intervals: preoperatively, after termination of the surgery, on the first, on the third and on the seventh postoperative day, respectively. Results: The most substantial changes appeared on the first postoperative day in both subgroups of patients. While the percentage of both total T cells and CD4+ T cells were decreased, the percentage of HLA-DR+ activated lymphocytes was increased. These changes were more profound in the “on-pump” subgroup compared to the “off-pump” subgroup. Conclusion: Our results may suggest that the “off-pump” surgical approach reveals less adverse impact on adaptive immune responses.

  1. Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

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    Cléber Sergio da Silva

    2010-01-01

    Full Text Available OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas. The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3, 35.5 (± 9.5, and 50 (± 11.2 years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3, cytotoxic lymphocytes (CD8, B lymphocytes (CD20, macrophages (CD68 and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control, at the intraepithelial lesion (CIN cases, and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05 in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05. CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

  2. 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

  3. Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival.

    Science.gov (United States)

    January

    2016-04-01

    codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double-blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile.

  4. Effects of microwave radiation on peripheral lymphocyte subpopulations in rats

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    Jin-ling YIN

    2011-10-01

    Full Text Available Objective To investigate the effects and mechanisms of microwave radiation on peripheral lymphocyte subpopulations in Wistar rats.Methods A total of 100 Wistar rats(180-220g were exposed to microwave with different average power densities of 5,10,30 and 60 mW/cm2,and sham exposure of 0mW/cm2 was performed in a control group at the same time.At day 1,7,14 and 28 after microwave irradiation,the changes in peripheral CD3+,CD4+,CD8+ T cells,ratio of CD4+/CD8+ and CD45RA+ B lymphocyte in rats were analyzed by flow cytometry(FCM.Results The CD3+ T cells decreased significantly in 10-30mW/cm2 groups at day 7 and in 5-30 mW/cm2 groups at day 14 after radiation as compared with control group(P < 0.05,and CD4+ T cells decreased significantly in 10mW/cm2 group at day 14 after radiation as compared with control group(P < 0.01.From day 1 to day 14 after radiation,CD8+ T cells showed a reduction in number in all irradiated groups when compared with the control,but statistical significance was only found in the 30mW/cm2 group(P < 0.05.The CD4+/CD8+ ratio increased in 5mW/cm2 group on day 1,while decreased significantly in 5-30mW/cm2 groups on day 14 after radiation as compared with control group(P < 0.05.After microwave exposure,however,CD45RA+ B cells in 30mW/cm2 group at day 1 and in 30-60mW/cm2 groups at day 14 after radiation increased significantly in a dose-dependent manner.Conclusion A definite dosage of microwave radiation,ranging from 5-60mW/cm2,may induce changes in subpopulations of peripheral lymphocytes and cause acute immune function impairment in rats.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  6. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    International Nuclear Information System (INIS)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael; Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele; Geinitz, Hans; Duma, Marciana N.

    2017-01-01

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3 + T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [de

  7. Clinical Significance of Preoperative Neutrophil Lymphocyte Ratio versus Platelet Lymphocyte Ratio in Patients with Small Cell Carcinoma of the Esophagus

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    Ji-Feng Feng

    2013-01-01

    Full Text Available Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various of cancers. The aim of this study was to determine the prognostic values of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR in patients with small cell carcinoma of the esophagus (SCCE. Preoperative NLR and PLR were evaluated in 43 patients with SCCE from January 2001 to December 2010. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. Patients with PLR ≥150 had significantly poorer (relapse-free survival RFS and (overall survival OS compared to patients with PLR <150. However, RFS or OS did not differ according to NLR categories (<3.5 and ≥3.5. The areas under the curve (AUC indicated that PLR was superior to NLR as a predictive factor. The results of the present study conclude that PLR is superior to NLR as a predictive factor in patients with SCCE.

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

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    Cesar Miguel Momesso dos Santos

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

  9. Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

    Science.gov (United States)

    Pilli, T; Toti, P; Occhini, R; Castagna, M G; Cantara, S; Caselli, M; Cardinale, S; Barbagli, L; Pacini, F

    2017-12-11

    An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

  10. 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

  11. Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.

    Science.gov (United States)

    Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U; Pinto, Jorge; Porto, Graça

    2015-01-01

    Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.

  12. 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

  13. 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.

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

    Science.gov (United States)

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

    2002-01-01

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

  15. Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

    Science.gov (United States)

    Liu, X; Liu, H; Guo, Z; Luan, W

    2006-01-01

    To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

  16. Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Todd NW

    2013-03-01

    Full Text Available Nevins W Todd,1,2 Rachel G Scheraga,1,3 Jeffrey R Galvin,1,4 Aldo T Iacono,1 E James Britt,1 Irina G Luzina,1,2 Allen P Burke,5,* Sergei P Atamas1,2,* 1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 2Baltimore VA Medical Center, Baltimore, MD, USA; 3Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; 4Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA *These authors contributed equally to this work Background: Idiopathic pulmonary fibrosis (IPF is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Methods: Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Results: Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively, and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013. Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte and CD20+ (B

  17. Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. III

    1988-01-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively

  18. Impaired T-lymphocyte colony formation by cord blood mononuclear cells

    International Nuclear Information System (INIS)

    Herrod, H.G.; Valenski, W.R.

    1982-01-01

    When compared to adult mononuclear cells, cord blood mononuclear cells demonstrated significantly decreased T-lymphocyte colony formation (1351 +/- 643 vs 592 +/- 862, P less than 0.01). This diminished colony-forming activity did not appear to be associated with impaired responsiveness to the stimulant phytohemagglutinin or with excessive suppressor-cell activity. Irradiation reduced the colony-forming capacity of cord blood mononuclear cells more than it did that of adult mononuclear cells. Depletion of adherent cells reduced cord blood mononuclear-cell colony-forming capacity by 40%, while similar treatment reduced adult colony formation by 10%. Lymphocyte proliferation in liquid culture of cord and adult cells was minimally affected by these procedures. The colony-forming capacity of cord blood could be enhanced by the addition of irradiated adult cells (284 +/- 72 vs 752 +/- 78, P less than 0.01). This enhancement was demonstrated to be due to a soluble factor produced by a population of irradiated adult cells depleted of the OKT8+ subpopulation of lymphocytes. These results indicate that the progenitor cells of T-lymphocyte colonies in cord blood have distinct biologic characteristics when compared to colony progenitors present in adult blood. This assay may prove to be useful in our efforts to understand the differentiation of T-cell function in man

  19. Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea.

    Science.gov (United States)

    Tan, Hui-Leng; Gozal, David; Wang, Yang; Bandla, Hari P R; Bhattacharjee, Rakesh; Kulkarni, Richa; Kheirandish-Gozal, Leila

    2013-06-01

    Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Cross-sectional. Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Consecutively recruited children being evaluated for habitual snoring. N/A. Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] hTST), moderate-severe OSA (AHI ≥ 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29). Pediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic

  20. 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

  1. 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

  2. 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)

  3. 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....

  4. 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)

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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)

  10. 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.

  11. 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...

  12. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  13. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    International Nuclear Information System (INIS)

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-01-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child

  14. 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 ...

  15. 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...

  16. 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...

  17. 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...

  18. Lymphocytic Esophagitis: An emerging clinicopathologic disease associated with dysphagia

    Science.gov (United States)

    Pasricha, Sarina; Gupta, Amit; Reed, Craig C.; Speck, Olga; Woosley, John T.; Dellon, Evan S.

    2016-01-01

    Background Lymphocytic Esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. Aim To characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. Methods We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000 and June 1, 2012. Archived pathology slides were re-reviewed and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Results 27 adults were diagnosed with LyE, and the majority were female (63%). The most common symptom was dysphagia (70%). 52% had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37%), erosive esophagitis (33%), rings (26%), and hiatal hernia (26%); 33% of patients required dilation. After histology re-review, 78% of LyE patients were found to have more than 20 lymphs/hpf. In comparison to the normal, reflux and EoE controls, patients with LyE tended to be non-white (pdysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. PMID:27343035

  19. Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

    Science.gov (United States)

    Pasricha, Sarina; Gupta, Amit; Reed, Craig C; Speck, Olga; Woosley, John T; Dellon, Evan S

    2016-10-01

    Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

  20. T CD3+CD8+ Lymphocytes Are More Susceptible for Apoptosis in the First Trimester of Normal Human Pregnancy

    Directory of Open Access Journals (Sweden)

    Dorota Darmochwal-Kolarz

    2014-01-01

    Full Text Available Aims. Normal human pregnancy is a complex process of many immunoregulatory mechanisms which protect fetus from the activation of the maternal immune system. The aim of the study was to investigate the apoptosis of lymphocytes in peripheral blood of normal pregnant patients and healthy nonpregnant women. Methods. Sixty pregnant women and 17 nonpregnant women were included in the study. Lymphocytes were isolated and labeled with anti-CD3, anti-CD4, and anti-CD8 monoclonal antibodies. Apoptosis was detected by CMXRos staining and analyzed using the flow cytometric method. Results. We found significantly higher apoptosis of total lymphocytes in peripheral blood of pregnant patients when compared to healthy nonpregnant women. The percentage of apoptotic T CD3+CD8+ cells in the first trimester was significantly higher when compared to the third trimester of normal pregnancy. The ratio of T CD3+CD4+ : T CD3+CD8+ apoptotic lymphocytes was significantly lower in the first trimester when compared to other trimesters of pregnancy and to both of the phases of the menstrual cycle. Conclusions. The higher apoptosis of T CD3+CD8+ lymphocytes and the lower ratio of T CD3+CD4+ : T CD3+CD8+ apoptotic cells in the first trimester of normal pregnancy may suggest a higher susceptibility of T CD3+CD8+ cells for apoptosis as a protective mechanism at the early stage of pregnancy.

  1. Prevention of lymphocyte apoptosis in septic mice with cancer increases mortality.

    Science.gov (United States)

    Fox, Amy C; Breed, Elise R; Liang, Zhe; Clark, Andrew T; Zee-Cheng, Brendan R; Chang, Katherine C; Dominguez, Jessica A; Jung, Enjae; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Linehan, David C; Coopersmith, Craig M

    2011-08-15

    Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.

  2. Protective effect of allium sativum ethanol extract on cultured human lymphocytes against electron beam radiation

    International Nuclear Information System (INIS)

    Rao, Shama; Shetty, Sukanya; Suchetha Kumari; Madhu, L.N.

    2013-01-01

    The development of radioprotective agent has been the subject of intense research because exposure to ionizing radiation causes DNA damage which may cause mutation and ultimately leads to cancer, on the other hand radiotherapy has become an integral part in treatment of cancer which uses ionizing radiations like X rays, gamma rays to kill the cancer cells. Amifostine is a well-known radioprotector which is clinically approved. There are many other radioprotectors like cysteine, cystamine, serotine but they are not used because of its normal tissue toxicity. Allium sativum is commonly known as garlic which has already been reported for its medicinal properties. In this study we evaluated radioprotection property of Allium sativum on DNA damage caused by electron beam radiation in cultured human lymphocytes. Allium sativum ethanol extract was used for this study. Cell viability was performed by MTT assay. DNA damage was assessed by comet assay parameters. The cultured lymphocytes were incubated with different concentrations 10, 50 and 100 μg/mL of Allium sativum extracts for 2, 4, 6 and 24 hour time intervals. Treatment of lymphocytes with various concentration of Allium sativum extract resulted in significant decrease in the level of DNA damage (Percentage tail DNA 6%) and increase in cell viability 93% (p>0.05) compare to the radiation control group. Results of this study revealed that Allium sativum protects cultured lymphocytes when exposed to electron beam radiation at its sub lethal dose. (author)

  3. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Yoon Hee Cho

    2016-02-01

    Full Text Available Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM, a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL, the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  4. GATA-3 EXPRESSION IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2010-01-01

    Full Text Available The aim of the study is to establish the features of expression of GATA-3 in peripheral lymphocytes from bronchial asthma patients (BA. Material and methods. 10 healthy controls, 15 patients with allergic (atopic and 15 persons with non-allergic BA were examined. A transcription factor GATA-3 expressed in peripheral lymphocytes was analyzed by Western blot after the lymphocytes were lysed. Preparation of cell lysates, and Western blotting were performed by means of a standard procedure (Amersham. An antibody against GATA-3 (Abcam, UK was used. Levels of the protein were analyzed versus β-actin levels using anti-actin antibody (Sigma Aldrich, USA. Results. Expression of GATA-3 was significantly increased in lymphocytes of patients with allergic BA as compared to healthy persons and non-allergic BA patients. The level of GATA-3 negatively correlated with the degree of airflow obstruction and positively correlated with dosage of parenteral steroids administered. Conclusion. GATA-3 may play a key role in the pathophysiology of BA. One may suggest that increased expression of GATA-3 transcription factor in atopic BA underlie high levels of Th2-cytokines production in allergic disease

  5. Reference ranges for lymphocyte subsets in healthy adult male Oman is

    International Nuclear Information System (INIS)

    Al-Jabri, Ali A.; Al-Shukaili, Ahmed K.; Al-Rashdi, Zowaina T.; Ganguly, Shyam S.

    2008-01-01

    Objective was to determine the reference ranges of lymphocyte subsets in serologically HIV-seronegative healthy male adults in Oman. A cohort, of 118 healthy male blood donors ranging in age from 18-51 years, was included in the study. The average was 25 years. Blood samples collected into tubes containing ethylene-diamine-tetra acetic acid were investigated for lymphocyte subsets using flow cytometer. This study was conducted in the Immunology Laboratory of Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman during the year 2006. For the 118 males investigated, the mean percentage and absolute values of the lymphocyte subsets were as follows: Cd3: 68.53+-7.5%, 1701+-489 cells/ul; CD8: 25.8+-5.9%, 638+-225 cells/ul; CD19: 13.7+-4.7%, 349+-158 cells/ul, CD56: 12.2+-6.7%, 308+-204 cells/ul. The ratio of CD4/CD8 was 1.6. Immunophenotyping has been used to establish reference values of lymphocyte subsets in normal healthy adult males in Oman. The Omani male reference values obtained in this study show wide variations compared with kits values previously used as reference. (author)

  6. Preliminary study on biological dosimetry using alkaline single cell gel electrophoresis of human peripheral lymphocytes

    International Nuclear Information System (INIS)

    Liu Qingjie; Lu Xue; Feng Jiangbing; Chen Deqing; Chen Xiaosui

    2006-01-01

    Objective: To explore the feasibility of alkaline single cell gel electrophoresis (SCGE) in biological dosimetry of ionizing radiation. Methods: Normal peripheral blood samples from two healthy males were exposed to different doses coblat-60 gamma-rays, ranged from 0 to 5 Gy, and the tail length (TL) and Oliver tail moment (TM) of the lymphocytes were analyzed with SCGE. The dose-effect curves of TL and TM were fitted respectively. The TL and TM of lymphocytes for eight radiation workers were analyzed with SCGE, cumulative doses were estimated using the fitted TL and TM equations, and then compared with the recorded monitoring doses. Results: The TLs or TMs of normal human lymphocytes were increased with the irradiation doses, and its relationship can be fitted with a linear-quadratic equations: Y=13.59 + 20.87X - 2.27 X 2 for TL, and Y = 8.50 + 15.04X - 1.43X 2 for TM, respectively (Y denotes TL or TM value, X is radiation dose). The doses estimated with TM equation were closer to the recorded monitoring doses than that with TL equation. Conclusions: The TM in lymphocytes analyzed with SCGE is a promising radiation biological dosimeter. (authors)

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

    Science.gov (United States)

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

    2017-03-09

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. 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.

  10. 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.

  11. 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.

  12. Age- and dose-related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Zhou, Ou-Liang; Kusunoki, Yoichiro; Kyoizumi, Seishi; Kohno, Nobuoki; Akiba, Suminori; Delongchamp, R.R.

    1988-07-01

    The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic bomb survivors. The study revealed a significant decrease in MLC with increasing dose of previous radiation exposure. This decline was remarkable in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T-cells for the immune system. Thus it may be that, in the advanced age ATB group, the thymus function has started to involute allowing less recovery of T-cell function compared to young survivors who have adequate processing T-cell activity. (author)

  13. Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts.

    Science.gov (United States)

    Silva, Luiz Arthur Barbosa da; Sá, Maria Alice Ramalho; Melo, Rafaela Albuquerque; Pereira, Joabe Dos Santos; Silveira, Éricka Janine Dantas da; Miguel, Márcia Cristina da Costa

    2017-12-18

    The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

  14. Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts

    Directory of Open Access Journals (Sweden)

    Luiz Arthur Barbosa da Silva

    2017-12-01

    Full Text Available Abstract: The aim of this study was to compare the number of CD57+ natural killer (NK cells and CD8+ T lymphocytes between periapical granulomas (PGs and radicular cysts (RCs. Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively. Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042. A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively. CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001. CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

  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. Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

    International Nuclear Information System (INIS)

    van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

    1980-01-01

    It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection

  17. 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

  18. 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 ...

  19. 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...

  20. 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

  1. 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...

  2. 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 ...

  3. 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

  4. 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 ...

  5. 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

  6. 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

  7. 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....

  8. 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

  9. 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

  10. Enhancing effects of thymopoietin and T cell growth factor on mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia

    International Nuclear Information System (INIS)

    Knox, S.J.; Greenberg, B.R.; Anderson, R.W.; Shifrine, M.

    1983-01-01

    Cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders are significantly depressed compared to normal values. TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the preleukemic patients studied, while there was little or no effect in control cultures. Enhancement of lymphocyte responsiveness with TP-5 and IL-2 suggests the presence of maturational/-functional defects in these patients which may be compensated for in part by addition of TP-5 and IL-2

  11. Cytokine profile and lymphocyte subsets in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  12. Cytogenetic biodosimetry using the blood lymphocytes of astronauts

    Science.gov (United States)

    George, Kerry A.; Rhone, Jordan; Chappell, Lori J.; Cucinotta, Francis A.

    2013-11-01

    Cytogenetic analysis of peripheral blood lymphocytes is the most sensitive and reliable method currently available for in vivo assessment of the biological effects of exposure to radiation and provides the most informative measurement of radiation induced health risks. Data indicates that space missions of a few months or more can induce measureable increases in the yield of chromosome damage in the blood lymphocytes of astronauts that can be used to estimate an organ dose equivalent, and biodosimetry estimates lie within the range expected from physical dosimetry. Space biodosimetry poses some unique challenges compared to terrestrial biological assessments of radiation exposures, but data provides a direct measurement of space radiation damage, which takes into account individual radiosensitivity in the presence of confounding factors such as microgravity and other stress conditions. Moreover if chromosome damage persists in the blood for many years, results can be used for retrospective dose reconstruction. In contrast to physical measurements, which are external to body and require multiple devices to detect all radiation types all of which have poor sensitivity to neutrons, biodosimetry is internal and includes the effects of shielding provided by the body itself plus chromosome damage shows excellent sensitivity to protons, heavy ions, and neutrons. In addition, chromosome damage is reflective of cancer risk and biodosimetry values can therefore be used to validate and develop risk assessment models that can be used to characterize health risk incurred by crewmembers. The current paper presents a review of astronaut biodosimetry data, along with recently derived data on the relative cancer risk estimated using the quantitative approach derived from the European Study Group on Cytogenetic Biomarkers and Health database.

  13. Detection of silver-stained nucleolar organizer regions in the peripheral blood T lymphocytes in nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Li Xianming; Wu Dong; Chen Shanyi; Ren Zheping; Chen Yixin; Wang Xiuqing

    2002-01-01

    Objective: To evaluate the clinical significance of detecting silver-stained nucleolar organizer regions (Ag-NOR) in the peripheral blood T lymphocytes in nasopharyngeal carcinoma (NPC) patients. Methods: Ag-NOR in the peripheral blood T lymphocytes detected in 36 healthy subjects served as control. Those in 73 newly diagnosed but untreated, 11 recurrent (and/or metastatic) and 32 treated NPC patients in follow-up were monitored. The dynamic variations in the level of Ag-NORs in the peripheral blood T lymphocytes in the pre-radiotherapy (pre-RT), during RT and post-RT were evaluated in part of the newly diagnosed patients. Results: The level of Ag-NORs in the peripheral blood T lymphocytes in all groups of NPC patients were significantly lower as compared to the health controls (P 0.05). The level of Ag-NORs during RT significantly decreased as compared to that of pre-RT (P 0.05). Conclusions: Detection of Ag-NORs in the peripheral blood T lymphocytes is of significance in evaluating the outcome, predicting prognosis and even in making the diagnosis and staging for NPC patients

  14. Change of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    Shi-Hua Zhou

    2016-01-01

    Objective:To analyze and investigate the change state of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion. Methods: A total of 92 patients with recurrent spontaneous abortion in our hospital from June 2013 to July 2015 were selected as the observation group and 92 women with health delivery history at the same time were selected as the control group,then the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of two groups were detected and compared and the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of patients with different gestational age at abortion and abortion times were compared too. Results:The peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of observation group and control group all had obvious differences,and those blood indexes levels' differences of patients with different gestational age at abortion and abortion times were obvious too, all P<0.05 and the differences were significant. Conclusions: The T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion show abnormal state and the differences of detection results of patients with different gestational age at abortion and abortion times are relatively obvious,so those indexes should be monitored and improved intentinonally.

  15. Modeling the Effect of the Selective S1P1 Receptor Modulator Ponesimod on Subsets of Blood Lymphocytes.

    Science.gov (United States)

    Lott, Dominik; Krause, Andreas; Seemayer, Christian A; Strasser, Daniel S; Dingemanse, Jasper; Lehr, Thorsten

    2017-03-01

    This analysis aimed at describing the effect of the selective sphingosine-1-phosphate receptor 1 modulator ponesimod on lymphocyte subsets in peripheral blood. As the involvement of different lymphocyte subsets varies among different autoimmune diseases, characterizing the effect of ponesimod on these may be beneficial in better understanding treatment effects. Three phase 1 clinical studies in healthy human subjects were pooled. Non-linear mixed-effects modeling techniques were used to study the effect of ponesimod on lymphocyte subsets such as B cells, T helper cells, T cytotoxic cells, and natural killer cells in a qualitative and quantitative manner. Indirect-response I max models including circadian variation best described the effect of ponesimod on lymphocyte subsets. B cells and T helper cells were shown to be more affected compared to T cytotoxic cells with respect to the maximum possible reduction (100% for B and T helper cells, 95% for T cytotoxic cells) and the concentration required to reach half the maximum effect. Inter-individual variability was found to be larger for T cytotoxic compared to T helper, and B cells. These first models for ponesimod on the level of lymphocyte subsets offer a valuable tool for the analysis and interpretation of results from ponesimod trials in autoimmune diseases.

  16. Neutrophil–lymphocyte ratio is associated with low high-density lipoprotein cholesterol in healthy young men

    Directory of Open Access Journals (Sweden)

    Duran Tok

    2014-04-01

    Full Text Available Objective: It has been reported that the neutrophil–lymphocyte ratio is significantly elevated in patients with low high-density lipoprotein cholesterol (<35 mg/dL. But in this study, some patients had hypertension that may have affected the neutrophil–lymphocyte ratio. This study consisted of 1274 asymptomatic healthy young men. In contrast with the previous study, we investigated the neutrophil–lymphocyte ratio in healthy young men with low high-density lipoprotein cholesterol compared with controls. Methods: We studied 1274 asymptomatic young males (military personnel screening who underwent routine health check-up. Of them, 102 subjects had low high-density lipoprotein cholesterol. Results: The neutrophil–lymphocyte ratio was significantly higher among the men with low high-density lipoprotein cholesterol than that of the control group (P < 0.001. Conclusion: We conclude that the neutrophil–lymphocyte ratio is significantly elevated in asymptomatic healthy young men with low high-density lipoprotein cholesterol compared with control participants.

  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. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

    2014-11-28

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

  19. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    International Nuclear Information System (INIS)

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. III; Sobel, B.E.; Bergmann, S.R.

    1987-01-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 ( 111 In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111 In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures

  20. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    International Nuclear Information System (INIS)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

    2014-01-01

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

  1. INFLUENCE OF MODIFIED BIOFLAVONOIDS UPON EFFECTOR LYMPHOCYTES IN MURINE MODEL OF CONTACT SENSITIVITY

    Directory of Open Access Journals (Sweden)

    D. Z. Albegova

    2015-01-01

    T-lymphocytes, as compared to quercetin dihydrate.

  2. Comparison of p53 levels in lymphocytes and in blood plasma of nuclear power plant workers

    International Nuclear Information System (INIS)

    Roessner, Pavel; Chvatalova, Irena; Schmuczerova, Jana; Milcova, Alena; Roessner, Pavel; Sram, Radim J.

    2004-01-01

    p53 levels were assessed in lymphocytes and in blood plasma of workers from two Czech nuclear power plants (NPP): 114 subjects working in Temelin and 108 subjects working in Dukovany. Ionizing radiation (IR) exposure data were available for 64 and 59 subjects working in the monitored zones from the NPP in Temelin and Dukovany, respectively. The short-term doses of IR for these subjects were 0.01 and 0.12 mSv, and the long-term doses were 0.46 and 5.68 mSv, in the Temelin and Dukovany NPP, respectively. As a control group, 46 subjects living in Ceske Budejovice, a city nearby the Temelin NPP, were analyzed. The concentration of p53 in lymphocytes was significantly higher in workers from the monitored zone in the Dukovany NPP (median value 6.4 pg/μg protein, P < 0.001) than in workers from the Temelin NPP (3.2 pg/μg) as well as in the control group (3.5 pg/μg). In contrast, plasma levels of p53 were comparable in the control group (median value 116 pg/ml plasma) and workers from the monitored zone of Dukovany NPP (102 pg/ml), but lower in workers from Temelin NPP (5 pg/ml). Other factors affecting p53 levels were studied. Smoking resulted in increased p53 lymphocyte levels. The effect of polymorphisms in metabolic and DNA repair genes on p53 levels was analyzed. The correlation was found between p53 levels in lymphocytes and p53 codon 72 polymorphism in subjects working in NPPs, but not in the control group. The results of measurement p53 levels in lymphocytes suggest that this biomarker could reflect the short-term as well as long-term effects of low doses IR. Its impact on human health should be further explored

  3. 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

  4. 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

  5. Inhibition of DNA repair by whole body irradiation induced nitric oxide leads to higher radiation sensitivity in lymphocytes

    International Nuclear Information System (INIS)

    Sharma, Deepak; Santosh Kumar, S.; Raghu, Rashmi; Maurya, D.K.; Sainis, K.B.

    2007-01-01

    Full text: It is well accepted that the sensitivity of mammalian cells is better following whole body irradiation (WBI) as compared to that following in vitro irradiation. However, the underlying mechanisms are not well understood. Following WBI, the lipid peroxidation and cell death were significantly higher in lymphocytes as compared to that in vitro irradiated lymphocytes. Further, WBI treatment of tumor bearing mice resulted in a significantly higher inhibition of EL-4 cell proliferation as compared to in vitro irradiation of EL-4 cells. The DNA repair was significantly slower in lymphocytes obtained from WBI treated mice as compared to that in the cells exposed to same dose of radiation in vitro. Generation of nitric oxide following irradiation and also its role in inhibition of DNA repair have been reported, hence, its levels were estimated under both WBI and in vitro irradiation conditions. Nitric oxide levels were significantly elevated in the plasma of WBI treated mice but not in the supernatant of in vitro irradiated cells. Addition of sodium nitroprusside (SNP), a nitric oxide donor to in vitro irradiated cells inhibited the repair of DNA damage and sensitized cells to undergo cell death. It also enhanced the radiation-induced functional impairment of lymphocytes as evinced from suppression of mitogen-induced IL-2, IFN-γ and bcl-2 mRNA expression. Administration of N G -nitro-L-arginine-methyl-ester(L-NAME), a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. Our results indicated that nitric oxide plays a role in the higher radiosensitivity of lymphocytes in vivo by inhibiting repair of DNA damage

  6. 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.

  7. 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.

  8. 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...

  9. [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.

  10. The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Behçet's syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Alan

    2015-12-01

    Full Text Available Behçet's syndrome (BS is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil-to-lymphocyte ratio (NLR, platelet-to-lymphocyte ratio (PLR, and mean platelet volume (MPV in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC, neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p  0.05. In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively. We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies.

  11. Diagnostic Accuracy of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Detecting Occult Papillary Thyroid Microcarcinomas in Benign Multinodular Goitres

    Directory of Open Access Journals (Sweden)

    Dimitrios K. Manatakis

    2018-01-01

    Full Text Available Objective. To investigate the diagnostic accuracy of neutrophil-to-lymphocyte (NLR and platelet-to-lymphocyte (PLR ratios in detecting occult papillary thyroid microcarcinomas in benign, multinodular goitres. Methods. 397 total thyroidectomy patients were identified from the institutional thyroid surgery database between 2007 and 2016 (94 males, 303 females, mean age 53 ± 14.5 years. NLR and PLR were calculated as the absolute neutrophil and absolute platelet counts divided by the absolute lymphocyte count, respectively, based on the preoperative complete blood cell count. Results. NLR was significantly higher in carcinomas and microcarcinomas compared to benign pathology (p=0.026, whereas a direct association could not be established for PLR. Both NLR and PLR scored low in all parameters of diagnostic accuracy, with overall accuracy ranging between 45 and 50%. Conclusions. As surrogate indices of the systemic inflammatory response, NLR and PLR are inexpensive and universally available from routine blood tests. Although we found higher NLR values in cases of malignancy, NLR and PLR cannot effectively predict the presence of occult papillary microcarcinomas in otherwise benign, multinodular goitres.

  12. Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

    Directory of Open Access Journals (Sweden)

    Pavlica Ljiljana

    2003-01-01

    Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

  13. Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase

    Directory of Open Access Journals (Sweden)

    Xiuying Li

    2016-01-01

    Full Text Available It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM, adipose tissue (AT, placenta (PL, and umbilical cord (UC to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT, an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs.

  14. 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.

  15. Lymphocyte concanavalin A capping: a similarity between Down's syndrome and early onset primary degenerative dementia.

    OpenAIRE

    Duijndam-van den Berge, M; Goekoop, J G

    1986-01-01

    Lymphocyte capping with concanavalin A was studied in adult patients with Down's syndrome and aged patients with primary degenerative dementia. In both disorders a decreased capping was found as compared with age-matched and clinically relevant control groups. Colchicine had a strong enhancing effect on capping in Down's syndrome. In primary degenerative dementia the enhancing effect of colchicine was restricted to a subgroup of patients with onset of the dementing illness before the age of 8...

  16. Progranulin Is a Novel Independent Predictor of Disease Progression and Overall Survival in Chronic Lymphocytic Leukemia

    OpenAIRE

    G?bel, Maria; Eisele, Lewin; M?llmann, Michael; H?ttmann, Andreas; Johansson, Patricia; Scholtysik, Ren?; Bergmann, Manuela; Busch, Raymonde; D?hner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; D?hrsen, Ulrich; D?rig, Jan

    2013-01-01

    Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linke...

  17. Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

    OpenAIRE

    Choi, Goda; van den Broek, Esther C; Stam, Olga CG; van Noesel, C.J.M.; Tonino, Sanne H.; Kater, Armon P.

    2015-01-01

    We present a patient with chemotherapy-refractory Chronic Lymphocytic Leukemia (CLL) in whom postmortem examination showed hepatosplenomegaly, with both multiple small-cellular CLL lesions and large-cellular, monoclonal T-cell infiltrates. Following this case, the co-incidence of T-cell malignancies and CLL was studied using Dutch and American cancer registry databases. Analysis showed an excess risk for T-cell malignancies in CLL patients, with increased standardized incidence ratios compare...

  18. Investigations on the influence of radiotherapy on the extent of DNA-repair in peripheral lymphocytes and tumor cells of patients with cancer

    International Nuclear Information System (INIS)

    Klein, W.; Koren, H.; Alth, G.; Klein, H.

    1977-02-01

    The influence of radiotherapy on DNA excision repair after setting UV-lesions in peripheral lymphocytes and tumor cells of 11 patients with different forms of cancer was investigated. The effect of short term radiotherapy was compared with that after irradiation over a longer period. Radiotherapy provoked inhibition of DNA repair in tumor cells in every case, whereas changes in lymphocytes were dependent on irradiation schedule. (author)

  19. 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

  20. 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

  1. Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin

    International Nuclear Information System (INIS)

    Morimoto, K.; Kaneko, T.; Iijima, K.; Koizumi, A.

    1984-01-01

    Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to gamma-rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohemagglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to gamma-rays or bleomycin in G0, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after gamma-ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (gamma-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age

  2. Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: A small randomized controlled trial

    Science.gov (United States)

    Creswell, J. David; Myers, Hector F.; Cole, Steven W.; Irwin, Michael R.

    2009-01-01

    Mindfulness meditation training has stress reduction benefits in various patient populations, but its effects on biological markers of HIV-1 progression are unknown. The present study tested the efficacy of an 8-week Mindfulness-based stress reduction (MBSR) meditation program compared to a 1-day control seminar on CD4+ T lymphocyte counts in stressed HIV infected adults. A single-blind randomized controlled trial was conducted with enrollment and follow-up occurring between November 2005 and December 2007. A diverse community sample of 48 HIV-1 infected adults was randomized and entered treatment in either an 8-week MBSR or a 1-day control stress reduction education seminar. The primary outcome was circulating counts of CD4+ T lymphocytes. Participants in the 1-day control seminar showed declines in CD4+ T lymphocyte counts whereas counts among participants in the 8-week MBSR program were unchanged from baseline to post-intervention (time × treatment condition interaction, p = .02). This effect was independent of antiretroviral (ARV) medication use. Additional analyses indicated that treatment adherence to the mindfulness meditation program, as measured by class attendance, mediated the effects of mindfulness meditation training on buffering CD4+ T lymphocyte declines. These findings provide an initial indication that mindfulness meditation training can buffer CD4+ T lymphocyte declines in HIV-1 infected adults. PMID:18678242

  3. Molecular evidence of inefficient transduction of proliferating human B lymphocytes by VSV-pseudotyped HIV-1-derived lentivectors

    International Nuclear Information System (INIS)

    Serafini, M.; Naldini, L.; Introna, M.

    2004-01-01

    Lentiviral vectors are attractive tools to transduce dividing and nondividing cells. Human tonsillar B lymphocytes have been purified and induced to proliferate by the addition of anti-CD40 + IL-4 or anti-CD40 + anti-μ signals and transduced at high MOI with a VSV pseudotyped lentivector carrying the eGFP gene under the control of the PGK promoter. Parallel cultures of PHA-stimulated T lymphocytes containing a comparable amount of cycling cells during the infection reached over 70% eGFP transduction. By contrast, only less than 3% B lymphocytes became eGFP positive after 7 days from transduction. Molecular analysis of the viral life cycle shows that cytoplasmic retrotranscribed cDNA and nuclear 2LTR circles are detectable at lower levels and for a shorter period of time in proliferating B cells with respect to proliferating T lymphocytes. Moreover, FACS-sorted eGFP-positive and negative B cell populations were both positive for the presence of retrotranscribed cDNA and 2LTR circles nuclear forms. By contrast, nested Alu-LTR PCR allowed us to detect an integrated provirus in FACS-sorted eGFP-positive cells only. Together with the demonstration that infection in saturation conditions led to an increase in the percentage of transduced cells (reaching 9%), these findings suggest that in proliferating B lymphocytes, lentiviral transduction is an inefficient process blocked at the early steps of the viral life cycle possibly involving partially saturable restriction factors

  4. 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.

  5. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rybkina, Valentina L.; Azizova, Tamara V.; Adamova, Galina V.; Teplyakova, Olga V.; Osovets, Sergey V.; Bannikova, Maria V. [Southern Urals Biophysics Institute, Ozyorsk, Chelyabinsk Region (Russian Federation); Scherthan, Harry; Meineke, Viktor; Doerr, Harald [University of Ulm, Bundeswehr Institute of Radiobiology, Munich (Germany); Zurochka, Alexander V. [Immunology Institute, Yekaterinburg (Russian Federation)

    2014-11-15

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  6. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Rybkina, Valentina L.; Azizova, Tamara V.; Adamova, Galina V.; Teplyakova, Olga V.; Osovets, Sergey V.; Bannikova, Maria V.; Scherthan, Harry; Meineke, Viktor; Doerr, Harald; Zurochka, Alexander V.

    2014-01-01

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  7. Sensitivity of human peripheral lymphocyte chromosomes to various X-ray doses and subsequent storage in Plexiglass or glass containers

    International Nuclear Information System (INIS)

    Ivanov, B.; Bulanova, M.; Geogieva, I.

    1979-01-01

    A study was performed to determine whether chromosomal aberrations produced in vitro by various X-ray doses in human lymphocytes were affected by post-irradiation storage of the blood in plastic or glass containers. Following X-ray doses of up to 400 R, the yields of cells with aberrations and the incidence of dicentrics, rings, interstitial deletions, symmetrical changes and chromosome fragments increased with dose. After storage of the irradiated lymphocytes in either Plexiglass or glass, the values for exchange aberrations, deletions and aberrant cells were compared. The only statistically significant difference was a slight increase in the percentage of aberrant cells stored in the plastic containers at the 400 R dose level. It was concluded that plastics appear to have a sensitizing effect on the genetic structure of the peripheral lymphocyte and thus the use of this material to store blood in biological dosimetry studies should be discouraged. (U.K.)

  8. [Effects of oil-refining microbes (genus Acinetobacter) on cytogenetical structures of human lymphocytes in cell cultures].

    Science.gov (United States)

    Il'inskikh, N N; Il'inskikh, E N; Il'inskikh, I N

    2012-01-01

    The objective of this study was to assess ability of oil-refining bacteria Acinetobacter calcoaceticus and A. valentis to induce karyopathological abnormalities and chromosomal aberrations in human lymphocyte cultures. It was found that the cultures infected with A. calcoaceticus showed significantly high frequencies of cytogenetical effects and chromosomal aberrant cells as compared to the intact cultures and cultures infected with A. valentis. The most of chromosomal aberrations, mainly chromatid aberrations, were located in 1 and 2 chromosomes. Moreover, the aberrations were detected in some specific chromosome areas. Abnormalities of mitotic cell division and nucleus morphology were determined in lymphocyte cultures infected with A. calcoaceticus. There were found significantly high frequencies of cells with micronuclei, nucleus protrusions, anaphase or metaphase chromosome and chromosomal fragments lagging as well as multipolar and C-mitoses. Thus, the oil-refining bacteria A. calcoaceticus in contrast to A. valentis demonstrated strong genotoxic effects in human lymphocyte cultures in vitro.

  9. Chemotherapy for Initial Induction Failures in Childhood Acute Lymphoblastic Leukemia: a Children’s Oncology Group Study (POG 8764)

    OpenAIRE

    Joyce, Michael; Pollock, Brad H.; Devidas, Meenakshi; Buchanan, George; Camitta, Bruce

    2013-01-01

    Children with acute lymphocytic leukemia (ALL) who fail to enter remission have a poor prognosis. In a previous study, 9 of 14 children with induction failure entered remission after teniposide (VM26) plus cytosine arabinoside (Ara-C). We attempted to confirm these results. Twenty children received teniposide (200 mg/m2/day IV) for 3 days and cytosine arabinoside (100 mg/m2/day continuous IV infusion) for 7 days. There were 3 complete and 3 partial responses. Two additional patients achieved ...

  10. Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

    Science.gov (United States)

    DeZern, Amy E; Williams, Katherine; Zahurak, Marianna; Hand, Wesley; Stephens, R Scott; King, Karen E; Frank, Steven M; Ness, Paul M

    2016-07-01

    Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting. © 2016 AABB.

  11. Lymphocyte subset abnormalities in multitransfused HIV-negative haemophilia A patients are not due to chronic hepatitis C virus infection

    NARCIS (Netherlands)

    Meijer, K; van der Meer, J; Smit, JW; Verspiek, SPJ; Haagsma, EB; Smid, WM

    Several abnormalities of immune parameters have been described in HIV-negative haemophiliacs, including changes in numbers of T4 and T8 cells, T4/T8 ratio and numbers of activated T cells, To assess the contribution of hepatitis C to these abnormalities, we compared lymphocyte subsets in 20

  12. Cytokine production by natural killer lymphocytes in follicular and luteal phase of the ovarian cycle in humans

    NARCIS (Netherlands)

    Bouman, A.; Moes, H; Heineman, MJ; De Leij, LFMH; Faas, MM

    PROBLEM: The aim of this study was to test the hypothesis that, during luteal phase of the ovarian cycle, as compared with follicular phase, the cytokine productive capacity of peripheral natural killer (NK)-lymphocytes in humans is shifted towards a "Th2-type"-like response. METHOD OF STUDY:

  13. Interleukin-15 differentially enhances the expression of interferon-gamma and interleukin-4 in activated human (CD4(+))T lymphocytes

    NARCIS (Netherlands)

    Borger, P; Kauffman, HF; Postma, DS; Esselink, MT; Vellenga, E

    In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-gamma (IFN-gamma) and IL-4 in activated human T lymphocytes. The effect of IL-15 was compared with IL-2 and IL-7, cytokines all known to use the IL-2 receptor gamma(C) chain. The results

  14. Managing inadequate responses to frontline treatment of chronic myeloid leukemia: a case-based review.

    Science.gov (United States)

    Bixby, Dale L

    2013-05-01

    The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, and dasatinib are the standard of care for treating patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML). Compared with interferon-based treatment, the previous standard of care, imatinib is associated with significantly higher cytogenetic response rates and prolonged overall survival. Nilotinib and dasatinib, both newer and more potent TKIs, significantly improve cytogenetic and molecular response rates compared with imatinib. Despite significant advances in CML treatment enabled by the TKIs, a fraction of patients who receive frontline treatment with a TKI demonstrate inadequate response. The reasons for this vary, but in many cases, inadequate response can be attributed to non-adherence to the treatment regimen, intolerance to the drug, intrinsic or acquired resistance to the drug, or a combination of reasons. More often than not, strategies to improve response necessitate a change in treatment plan, either a dose adjustment or a switch to an alternate drug, particularly in the case of drug intolerance or drug resistance. Improved physician-patient communication and patient education are effective strategies to address issues relating to adherence and intolerance. Because inadequate response to TKI treatment correlates with poor long-term outcomes, it is imperative that patients who experience intolerance or who fail to achieve appropriate responses are carefully evaluated so that appropriate treatment modifications can be made to maximize the likelihood of positive long-term outcome. Copyright © 2012. Published by Elsevier Ltd.

  15. Improvement of techniques for the detection of radio-induced micronuclei in human blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Voisin, P.; Paillole, N.

    1995-12-31

    Scoring of micronuclei in cytokinesis-blocked peripheral human lymphocytes, after an accidental overexposure, seems an easier and faster alternative for biological dosimetry than conventional cytogenetics (dicentric chromosomes). Several variations of the cytokinesis-block micronucleus assay have been tested, in order to obtain a sufficient number of micronuclei in bi-nucleated cells by the shortest time possible for operational purposes. The methods differ in the use of hypotonic treatment as well as culture time (48 to 72 h), amount of blood and materials used. We have compared frequencies of bi-nucleated cells and micronuclei in normal lymphocytes and after {gamma}-({sup 60}Co) irradiation in vitro with {sup 60}Co for doses up to 6 Gy. Main results and the final choice of the technique are presented. (authors). 3 refs., 3 figs.

  16. Improvement of techniques for the detection of radio-induced micronuclei in human blood lymphocytes

    International Nuclear Information System (INIS)

    Voisin, P.; Paillole, N.

    1995-01-01

    Scoring of micronuclei in cytokinesis-blocked peripheral human lymphocytes, after an accidental overexposure, seems an easier and faster alternative for biological dosimetry than conventional cytogenetics (dicentric chromosomes). Several variations of the cytokinesis-block micronucleus assay have been tested, in order to obtain a sufficient number of micronuclei in bi-nucleated cells by the shortest time possible for operational purposes. The methods differ in the use of hypotonic treatment as well as culture time (48 to 72 h), amount of blood and materials used. We have compared frequencies of bi-nucleated cells and micronuclei in normal lymphocytes and after γ-( 60 Co) irradiation in vitro with 60 Co for doses up to 6 Gy. Main results and the final choice of the technique are presented. (authors). 3 refs., 3 figs

  17. In vitro susceptibilities in lymphocytes from mothers and cord blood to the monofunctional alkylating agent EMS

    DEFF Research Database (Denmark)

    Wyatt, N P; Falque-Gonzalez, C; Farrar, D

    2007-01-01

    at the Bradford Royal Infirmary collected venous blood samples from mothers at the time of birth and venous cord blood post-delivery. Lymphocytes were isolated from both blood types and examined in the alkaline comet assay using the monofunctional alkylating agent ethyl methanesulphonate (EMS). There were...... no biologically significant differences when subjects were categorized into subgroups based on lifestyle habits and physical characteristics, and overall there were no statistically significant differences in levels of DNA damage in mothers (n=22) and babies (n=22), except at the basal level (P... values in babies were always lower over the EMS dose range. Whole blood was used in the micronucleus (MN) assay, and there was a significantly (Prate of MN in mothers (n=17), per 1000 binucleates, as compared with lymphocytes from their offspring (n=17) at the basal level. This may...

  18. [Significance of the alteration of Th17 cells in patients with chronic lymphocytic thyroiditis].

    Science.gov (United States)

    Song, Jin-Zhan; Wu, Han-Ni; Qian, Wei

    2009-10-01

    To investigate the alteration and its significance of T help 17 cells (Th17) in patients with chronic lymphocytic thyroiditis (CLT). Patients were divided into 3 groups: CLT patients with euthyroidism (n=15), CLT patients with hypothyroidism (n=30) and healthy control group (n=20). The ratio of Th17 lymphocytes subpopulations in the peripheral blood were evaluated by technique of flow cytometry. Production of thyroid autoantibody (TPO-Ab, TG-Ab) were measured by electro-chemiluminescence immunoassay (ECLIA). Compared with the healthy control group, in CLT group: The frequencies of Th17 in peripheral blood were found to be significantly higher in patients with CLT than healthy control group (PCLT patients than healthy control group (PCLT which may suggest a potential role for Th17 in the progression and happen of CLT.

  19. Leukocyte counts and lymphocyte subsets in relation to pregnancy and HIV infection in Malawian women.

    Science.gov (United States)

    Mandala, Wilson L; Gondwe, Esther N; Molyneux, Malcolm E; MacLennan, Jenny M; MacLennan, Calman A

    2017-09-01

    We investigated leukocyte and lymphocyte subsets in HIV-infected or HIV-uninfected, pregnant or non-pregnant Malawian women to explore whether HIV infection and pregnancy may act synergistically to impair cellular immunity. We recruited 54 pregnant and 48 non-pregnant HIV-uninfected women and 24 pregnant and 20 non-pregnant HIV-infected Malawian women. We compared peripheral blood leukocyte and lymphocyte subsets between women in the four groups. Parturient HIV-infected and HIV-uninfected women had more neutrophils (each PHIV-uninfected parturient women had fewer CD4 + and γδ T cells, B and NK cells (each Ppregnancy. Malawian women at parturition have an increased total white cell count due to neutrophilia and an HIV-unrelated pan-lymphopenia. © 2017 The Author. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

  20. Mutagen-induced sister chromatid exchanges in xeroderma pigmentosum and normal lymphocytes

    International Nuclear Information System (INIS)

    Perry, P.E.; Jager, M.; Evans, H.J.

    1978-01-01

    The induction of sister chromatid exchanges (SCE), by ultra-violet irradiation and by three chemical mutagens that differ in the type of repair response that they elicit, has been compared in lymphocytes from a control and from an individual suffering from the DNA excision repair deficiency syndrome, xeroderma pigmentosum (XP). The XP lymphocytes were found to be more sensitive in terms of SCE response, not only to UV irradiation, but also to all of the chemicals studied. The results indicate that the abnormality of DNA repair in this XP patient is expressed not only in the defective excision of thymine dimers, or other UV photoproducts, but also in a reduced ability to repair other types of DNA lesion. (author)

  1. 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

  2. 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

  3. The mitogenic response of cryopreserved human lymphocytes in a microculture system.

    Science.gov (United States)

    Steel, C M; Ennis, M; Levin, A G; Wasunna, A

    1977-01-01

    Fresh blood lymphocytes from nine health donors have been compared with samples from the same donors, recovered after period of 2 to 21 months storage in liquid nitrogen, for the capacity to respond to a range of mitogens in vitro. A microculture assay was used, requireing aliquots of only 25,000 cells. The mean levels of 14C-thymidine uptake for fresh and frozen samples were closely comparable when the cells had been stimulated by PHA, Pokeweed or mitomycin-C-treated allogeneic lymphoblastoid cells. Lymphocytes from six East African donors, frozen by a very simple technique, were recovered after 3 or more years storage in liquid nitrogen. Five of the samples were in good condition as judged by cell viability and the capacity to form spontaneous 'E' rosettes with sheep erythrocytes. These five samples also responded extremely well to PHA, PWM and mitomycin-C-treated allogeneic lymphoblastoid cells using the microculture assay. This study extends the range of applications of cell banks in which small aliquots of blood lymphocytes are stored in liquid nitrogen for periods of several years.

  4. Micronuclei frequencies in lymphocytes and cervical cells of women with polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Rengin Karataylı

    2017-09-01

    Full Text Available Objective: The aim of this study was to determine micronucleus (MN frequencies in exfoliated cervical cells and peripheral blood lymphocytes of women with polycystic ovarian syndrome (PCOS. Materials and Methods: Fifteen patients with PCOS and 11 healthy control patients were included in the study. Cervical smears and peripheral blood were collected from all patients. Specimens were analyzed for MN frequencies and compared between the groups. In addition to MN, other nuclear anomalies connected with both genotoxicity and cytotoxicity were evaluated. Results: The MN frequencies in cervical smear and peripheral blood lymphocytes were compared in patients with PCOS and normal controls. There was no statistically significant difference between the groups regarding micronucleus frequency in peripheral blood lymphocytes (p=0.239. The mean MN scores in exfoliated cervical cells of patients with PCOS and normal controls were 1.19±0.57 and 0.74±0.34, respectively. The difference regarding micronucleus frequencies in cervical cells was statistically significant between the groups (p=0.032. Conclusion: Although study group is small, our study results support that there is an increased micronucleus frequency in cervical exfoliated cells of PCOS patients; this is a determinant of genetic hazard in the disease.

  5. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Science.gov (United States)

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  6. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Directory of Open Access Journals (Sweden)

    Denise Silveira-Lemos

    2013-01-01

    Full Text Available Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group before and after praziquantel treatment (ACT-TR group. Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA, increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

  7. Association of body mass index and survival in pediatric leukemia: a meta-analysis.

    Science.gov (United States)

    Orgel, Etan; Genkinger, Jeanine M; Aggarwal, Divya; Sung, Lillian; Nieder, Michael; Ladas, Elena J

    2016-03-01

    Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemia-related mortality; whether a similar effect exists in childhood leukemia remains controversial. We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0-21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese (≥95%) or overweight/obese (≥85%), was compared with lower BMI [nonoverweight/obese (children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML. © 2016 American Society for Nutrition.

  8. Long-term medical costs and life expectancy of acute myeloid leukemia: a probabilistic decision model.

    Science.gov (United States)

    Wang, Han-I; Aas, Eline; Howell, Debra; Roman, Eve; Patmore, Russell; Jack, Andrew; Smith, Alexandra

    2014-03-01

    Acute myeloid leukemia (AML) can be diagnosed at any age and treatment, which can be given with supportive and/or curative intent, is considered expensive compared with that for other cancers. Despite this, no long-term predictive models have been developed for AML, mainly because of the complexities associated with this disease. The objective of the current study was to develop a model (based on a UK cohort) to predict cost and life expectancy at a population level. The model developed in this study combined a decision tree with several Markov models to reflect the complexity of the prognostic factors and treatments of AML. The model was simulated with a cycle length of 1 month for a time period of 5 years and further simulated until age 100 years or death. Results were compared for two age groups and five different initial treatment intents and responses. Transition probabilities, life expectancies, and costs were derived from a UK population-based specialist registry-the Haematological Malignancy Research Network (www.hmrn.org). Overall, expected 5-year medical costs and life expectancy ranged from £8,170 to £81,636 and 3.03 to 34.74 months, respectively. The economic and health outcomes varied with initial treatment intent, age at diagnosis, trial participation, and study time horizon. The model was validated by using face, internal, and external validation methods. The results show that the model captured more than 90% of the empirical costs, and it demonstrated good fit with the empirical overall survival. Costs and life expectancy of AML varied with patient characteristics and initial treatment intent. The robust AML model developed in this study could be used to evaluate new diagnostic tools/treatments, as well as enable policy makers to make informed decisions. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. 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

  10. 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.

  11. 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

  12. 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)

  13. The influences of age on T lymphocyte subsets in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Jing Xie

    2017-01-01

    Full Text Available The aim of this study is to evaluate the age related changes of T lymphocyte subsets in C57BL/6 mice and immune function. Multi-color immunofluorescence techniques that were used to analyse relative numbers of T lymphocyte subsets include CD4+, CD8+, naive and memory CD4+ and CD8+, CD8+CD28+ T cells in peripheral blood of C57BL/6 mice from different age groups (Group I: 2 months old; Group II: 7 months old; Group III: 21 months old; Splenocytes isolated from different group mice were stimulated with Con A to evaluate the proliferative ability. Compared with group I, group II had a significant reduction in the percentage of CD4+, naive CD4+ and CD8+ T cells and an increase in the percentage of CD8+ T cells, while group III had a significant reduction in the percentage of CD4+, naive CD4+ and CD8+ T cells and increase in the percentage of CD8+, memory CD4+ and CD8+ T cells in peripheral blood. Compared with group II, group III had a significant reduction in the percentage of naive CD8+ T cells and increase in the percentage of memory CD4+ and CD8+, CD8+CD28+ T cells in peripheral blood. The T lymphocyte proliferation in vitro showed that groups II and III had a lower proliferative capacity than group I, between groups II and III, there was not a significant difference. We provide relative values for the T lymphocyte subsets in the different age groups of C57BL/6 mice. The immune system began aging at 7 months old in C57BL/6 mice under a specific pathogen free environment.

  14. DNA-protein crosslinks in peripheral lymphocytes of individuals exposed to hexavalent chromium compounds.

    Science.gov (United States)

    Zhitkovich, A; Lukanova, A; Popov, T; Taioli, E; Cohen, H; Costa, M; Toniolo, P

    1996-01-01

    Abstract DNA-protein crosslinks were measured in peripheral blood lymphocytes of chrome-platers and controls from Bulgaria in order to evaluate a genotoxic effect of human exposure to carcinogenic Cr(VI) compounds. Chrome-platers and most of the unexposed controls were from the industrial city of Jambol; some additional controls were recruited from the seaside town of Burgas. The chrome-platers had significantly elevated levels of chromium in pre- and post-shift urine, erythrocytes and lymphocytes compared with the control subjects. The largest differences between the two groups were found in erythrocyte chromium concentrations which are considered to be indicative of Cr(VI) exposure. Despite the significant differences in internal chromium doses, levels of DNA-protein crosslinks were not significantly different between the combined controls and exposed workers. Individual DNA-protein crosslinks, however, correlated strongly with chromium in erythrocytes at low and moderate doses but at high exposures, such as among the majority of chrome-platers, these DNA adducts were saturated at maximum levels. The saturation of DNA-protein crosslinks seems to occur at 7-8 μg I-(1) chromium in erythrocytes whereas a mean erythrocyte chromium among the chrome platers was as high as 22.8 μg l(-1). Occupationally unexposed subjects exhibited a significant variability with respect to the erythrocyte chromium concentration, however erythrocyte chromium levels correlated closely with DNA-protein crosslinks in lymphocytes. The controls from Jambol had higher chromium concentrations in erythrocytes and elevated levels of DNA-protein crosslinks compared with Burgas controls. Occupational exposure to formaldehyde among furniture factory workers did not change levels of DNA-protein crosslinks in peripheral lymphocytes. DNA-protein crosslink measurements showed a low intraindividual variability and their levels among both controls and exposed indivduals were not affected by smoking, age

  15. Mercury toxicity in beluga whale lymphocytes: Limited effects of selenium protection

    Energy Technology Data Exchange (ETDEWEB)

    Frouin, H. [Fisheries and Oceans Canada, Institute of Ocean Sciences, 9860 West Saanich Rd, P.O. Box 6000, Sidney, BC, V8L 4B2 (Canada); Loseto, L.L.; Stern, G.A. [Fisheries and Oceans Canada, Freshwater Institute, 501 University Crescent, Winnipeg, MB, R3T 2N6 (Canada); Haulena, M. [Vancouver Aquarium, 845 Avison Way, Vancouver, BC, V6G 3E2 (Canada); Ross, P.S., E-mail: peter.s.ross@dfo-mpo.gc.ca [Fisheries and Oceans Canada, Institute of Ocean Sciences, 9860 West Saanich Rd, P.O. Box 6000, Sidney, BC, V8L 4B2 (Canada)

    2012-03-15

    Increasing emissions of anthropogenic mercury represents a growing concern to the health of high trophic level marine mammals. In its organic form, this metal bioaccumulates, and can be toxic to several physiological endpoints, including the immune system. In this study, we (1) evaluated the effects of inorganic mercury (mercuric chloride, HgCl{sub 2}) and organic mercury (methylmercuric chloride, MeHgCl) on the in vitro function of lymphocytes isolated from the peripheral blood of beluga whales (Delphinapterus leucas); (2) characterized the potential protective effects of sodium selenite (Na{sub 2}SeO{sub 3}) on cell proliferation of HgCl{sub 2} or MeHgCl-treated beluga whale lymphocytes; and (3) compared these dose-dependent effects to measurements of blood Hg in samples collected from traditionally harvested beluga whales in the western Canadian Arctic. Lymphocyte proliferative responses were reduced following exposure to 1 {mu}M of HgCl{sub 2} and 0.33 {mu}M of MeHgCl. Decreased intracellular thiol levels were observed at 10 {mu}M of HgCl{sub 2} and 0.33 {mu}M of MeHgCl. Metallothionein induction was noted at 0.33 {mu}M of MeHgCl. Concurrent exposure of Se provided a degree of protection against the highest concentrations of inorganic Hg (3.33 and 10 {mu}M) or organic Hg (10 {mu}M) for T-lymphocytes. This in vitro protection of Se against Hg toxicity to lymphocytes may contribute to the in vivo protection in beluga whales exposed to high Hg concentrations. Current Hg levels in free-ranging beluga whales from the Arctic fall into the range of exposures which elicited effects on lymphocytes in our study, highlighting the potential for effects on host resistance to disease. The implications of a changing Arctic climate on Hg fate in beluga food webs and the consequences for the health of beluga whales remain pressing research needs.

  16. Mercury toxicity in beluga whale lymphocytes: Limited effects of selenium protection

    International Nuclear Information System (INIS)

    Frouin, H.; Loseto, L.L.; Stern, G.A.; Haulena, M.; Ross, P.S.

    2012-01-01

    Increasing emissions of anthropogenic mercury represents a growing concern to the health of high trophic level marine mammals. In its organic form, this metal bioaccumulates, and can be toxic to several physiological endpoints, including the immune system. In this study, we (1) evaluated the effects of inorganic mercury (mercuric chloride, HgCl 2 ) and organic mercury (methylmercuric chloride, MeHgCl) on the in vitro function of lymphocytes isolated from the peripheral blood of beluga whales (Delphinapterus leucas); (2) characterized the potential protective effects of sodium selenite (Na 2 SeO 3 ) on cell proliferation of HgCl 2 or MeHgCl-treated beluga whale lymphocytes; and (3) compared these dose-dependent effects to measurements of blood Hg in samples collected from traditionally harvested beluga whales in the western Canadian Arctic. Lymphocyte proliferative responses were reduced following exposure to 1 μM of HgCl 2 and 0.33 μM of MeHgCl. Decreased intracellular thiol levels were observed at 10 μM of HgCl 2 and 0.33 μM of MeHgCl. Metallothionein induction was noted at 0.33 μM of MeHgCl. Concurrent exposure of Se provided a degree of protection against the highest concentrations of inorganic Hg (3.33 and 10 μM) or organic Hg (10 μM) for T-lymphocytes. This in vitro protection of Se against Hg toxicity to lymphocytes may contribute to the in vivo protection in beluga whales exposed to high Hg concentrations. Current Hg levels in free-ranging beluga whales from the Arctic fall into the range of exposures which elicited effects on lymphocytes in our study, highlighting the potential for effects on host resistance to disease. The implications of a changing Arctic climate on Hg fate in beluga food webs and the consequences for the health of beluga whales remain pressing research needs.

  17. Changes in lymphocyte subsets during pregnancy and post-partum in cases of beginning eclampsia.

    Science.gov (United States)

    Kühnert, M; Schmidt, S

    2000-01-01

    The goal of the present retrospective study was to examine the peripheral blood lymphocytes for expression of phenotypic and activation markers concerning the development of hypertension in pregnancy. 16 women (aged 25-43 years; mean 35.1) developing hypertension in the third trimester (week 25-34) have had blood samples taken in the first (post-partum, The control group consisted of 16 age-matched pregnant healthy women, who underwent the same regime. All blood samples were taken in the morning, stored at room temperature and stained within 6 hours and measured within 24 hours. Kruskal-Wallis analysis of variance between both groups was done with multiple comparison according to Dunn. Comparing both groups, the total white cell count was significantly increased in all pregnancies and post-partum. In case of hypertension in pregnancy the cell numbers of suppressor/cytotoxic (CD 8+) and CD 56(+)-activated T cells showed a significant increase in the first trimester (< 14 weeks) [p < 0.05] and decreased thereafter to normal values. In the second trimester (week 14-23) helper/inducer lymphocytes and CD 56+/CD 3+ lymphocytes decreased in case of pre-ecclampsia and cytotoxic lymphocytes elevated [p < 0.05]. In the third trimester (week 24-35) there was no difference in both study groups and in late pregnancy (week 36-termination) there were only small differences without statistical significance. Within 1 week postnatal the value of Il-2 receptor T lymphocytes decreased in the group of pre-eclampsia in comparison to normal pregnancies [p < 0.05]. Regarding the major changes in activated T cells in both study groups no specific pattern of lymphocyte subsets in case of pre-eclampsia could be found in comparison to healthy pregnant women. Further investigations should focus on functional activation and/or suppression of the cellular immune system. Perhaps this could lead to a screening test for pre-eclampsia in future, which is non-invasive for the patient and economic for

  18. Influence of occupational exposure to pesticides on the level of DNA damage induced in human lymphocytes (Polish group) by UV-C and X-rays

    International Nuclear Information System (INIS)

    Dyga, W.; Drag, Z.; Cebulska-Wasilewska, A.

    2002-01-01

    The aim of this study was to find out whether occupational exposure to pesticides might affect the individual susceptibility of various donors to the induction of DNA damage by genotoxic agents (UV-C, X-rays) and the efficiency of cellular repair. Previously cryo preserved lymphocytes were defrosted, and DNA damage in the lymphocytes prior to any in vitro studies was investigated with the application of the Comet assay. In order to evaluate the susceptibilities of human lymphocytes to genotoxic agents and the variability of repair capacities, the DNA migrations were estimated immediately after exposure to UV-C light or X-rays and after two hours. On average, the DNA damage detected in untreated lymphocytes was significantly higher in the group exposed to pesticides than in reference group. UV-C treated lymphocytes from group exposed to pesticides shows a greater statistically significant level of DNA migration compared to the reference group, detected after 2 hours incubation in the absence of PHA. Significantly lower responses to X-rays and higher levels of residual DNA damage were detected in the lymphocytes of donors from the group exposed to pesticides compared with the reference group. In conclusion, our results suggest that occupational exposure to pesticides influences the level of induced DNA damage, and the cellular capabilities of repair. (author)

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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...

  4. 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.

  5. 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...

  6. 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

  7. 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.

  8. 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.)

  9. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

    Science.gov (United States)

    Gudzenko, N; Hatch, M; Bazyka, D; Dyagil, I; Reiss, R F; Brenner, A; Chumak, V; Babkina, N; Zablotska, L B; Mabuchi, K

    2015-10-01

    Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

    Directory of Open Access Journals (Sweden)

    Helen C. Atkinson

    2015-01-01

    Full Text Available Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL and treated with modern COG protocols (n=80 to determine longitudinal changes in body mass index (BMI and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5% were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004 for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7. Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005, disease risk (P<0.0001, age (P=0.0001, and BMI z-score (P<0.0001 at diagnosis and total dose of steroid during maintenance (P=0.01. Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  11. 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

  12. 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.

  13. 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

  14. [Evaluation of percentage of lymphocytes B with expression of co-receptors CD 40, CD22 and CD72 in hypertrophied adenoid at children with otitis media with effusion].

    Science.gov (United States)

    Wysocka, Jolanta; Zelazowska-Rutkowska, Beata; Ratomski, Karol; Skotnicka, Bozena; Hassmann-Poznańska, Elzbieta

    2009-01-01

    In hypertrophied adenoid lymphocytes B make up about 60% all lymphocytes. When the lymphocytes B come in interaction with antigens this membranes signal be passed through their receptor (BCR) to interior of cell. This signal affect modulation on gene expression, activation from which depends activation, anergy or apoptosis of lymphocyte B. Accompany BCR co-receptors regulate his functions influence stimulate or inhibitive. To the most important co-receptors stepping out on lymphocyte B belong: CD40, CD22, CD72. The aim of study was evaluation of lymphocytes B (CD19) with co-expression with CD72 and CD40 receptors in hypertrophied adenoid with at children with otitis media with effusion. An investigation was executed in hypertrophied adenoids with or without otitis media with effusion. By flow cytometry percentage of lymphocytes B with co-receptors CD 40, CD22 and CD72 in was analyzed. The percentages of CD19+CD72+ lymphocytes in the group of children with adenoid hypertrophy and exudative otitis media were lower as compared to the reference group. However, the percentages of CD19+CD22+, CD19+CD40+ in the study group was approximate to the reference group. The lower percentage of lymphocytes B CD72 + near approximate percentages of lymphocytes B CD40+ and BCD22+ at children with otitis media with effusion can be the cause of incorrect humoral response in hypertrophied adenoid at children. Maybe it is cause reduced spontaneous production IgA and IgG through lymphocyte at children with otitis media with effusion.

  15. Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation.

    Directory of Open Access Journals (Sweden)

    Jacek M Witkowski

    2008-01-01

    Full Text Available Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+ cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.

  16. 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...

  17. Hematopoietic stem cell transplantation in children with leukemia: a single institution experience with respect to donors.

    Science.gov (United States)

    Baek, Hee Jo; Kook, Hoon; Han, Dong Kyun; Hwang, Tai Ju

    2011-12-01

    Aim of this study was to compare the outcomes of transplantation by donor source and to help select the best alternative donor in children with leukemia. Donor sources included matched related donor (MRD, n = 35), allele-matched unrelated donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II-IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB, 54.4%, P = 0.004) but there was no difference in incidence of chronic graft versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was 76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%, and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was 2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations of small number of patients, unrelated donor transplants including even allele-mismatched ones, seem to be as effective in children with leukemia lacking suitable relative donors. Also, UCB transplant may serve as another possible option in urgent transplants.

  18. The effects of radioiodine therapy on peripheral blood lymphocyte subpopulations in patients with Graves' disease. Preliminary report

    International Nuclear Information System (INIS)

    Turowska, M.D.; Rogowski, F.; Turowski, D.; Wysocka, J.

    2002-01-01

    Treatment of Graves' disease patients with radioactive iodide ( 131 I) is becoming the standard therapy in an increasing group of cases but can induce alterations in immune response, like increasing levels of thyroid autoantibodies, and, in part, exacerbation of ophthalmopathy. The aim of this study was to assess the changes in peripheral blood (PB) lymphocyte subpopulations after 131 I treatment of patients with Graves' disease. The study was carried out in a group of 30 patients with Graves' disease (23 f; 7 m) 49.5±10.0 years of age, 26 with different subjective ocular signs like gritty sensation, increased lacrimation, orbital pain, and exophthalmos. PB lymphocyte subsets were analysed by cytofluorometry, serum concentration of TSH and fT4 were evaluated before and 6 weeks after radioiodine treatment. After 131 I treatment a significant increase in CD3+, CD4+, CD3+HLA-DR+ and a decrease in CD19+ percentages of lymphocyte subsets were found in comparison with the initial evaluation. No significant changes in percentage of CD8+ and NK (CD3-CD16+ CD56+) cells were observed during this study. A significant increase in TSH and a slight decrease in fT4 concentration concentration took place in the 6th week after 131 I application. The patients without subjective improvement of ocular signs during the therapy initially had a percentage of CD3+, CD8+ lymphocytes which was significantly lower compared with those with regression of ocular signs observed after 131 I treatment. The changes in PB lymphocyte subsets caused by 131 I treatment of Graves' disease confirm the involvement of acquired cellular immunity after radiation damage of the thyroid gland. The decreased initial percentage of CD8+ and CD3+ lymphocytes could help make a prediction of ocular symptoms persisting after radioiodine treatment in some patients with ophthalmopathy. (author)

  19. 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.

  20. Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

    Science.gov (United States)

    Gladstone, Douglas E; Fuchs, Ephraim

    2012-03-01

    Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

  1. Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

    Science.gov (United States)

    Trautmann, A; Seitz, C S; Stoevesandt, J; Kerstan, A

    2014-12-01

    The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions. © 2014 John Wiley & Sons Ltd.

  2. Dysregulation of T lymphocyte proliferative responses in autoimmunity.

    Directory of Open Access Journals (Sweden)

    Sydney K Elizer

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

  3. Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

    Directory of Open Access Journals (Sweden)

    Maria Isabel de Moraes-Pinto

    2014-12-01

    Full Text Available Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009, which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.

  4. Influence of X-ray on the P53 gene in human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Jin Wenwei; Cai Ting

    2002-01-01

    Objective: To evaluate the reliability and safety of varying X-ray dosage. Methods: peripheral lymphocytes of five healthy volunteers were processed by varying X-rays, then detect the P53 gene mutation in 5-9 exons by PCR-SSCP silver staining, investigate the 249 th codon's mutation by PCR-RFLP, through immunohistochemistry staining monitor the abnormal expression of P53 and screen the apoptosis employing the Bio-dUTP terminal labelling technology included by DNA terminal transferase. Results: The frequency of apoptosis represents transparent dose-dependent manner with X-ray. When exposed to X-ray > 50 cGy after 48 h, the apoptosis group has evident difference compared with the control (P 0.05). After treating peripheral lymphocytes with 5-200 cGy X-ray and culturing 96 h, utilizing PCR-SSCP to determine the mutation in 5-9 exons, there was no single strand DNA abnormal migration. PCR-RFLP result indicates no mutation in the hotspot site-249 codon, and there was no obviously abnormal expression of P53 in immunohistochemistry staining. Conclusions: The apoptosis of peripheral lymphocytes is sensitive to the X-ray, and this can be a guideline or model reflecting the body state when exposing to the radiation

  5. Effect of radiotherapy on lymphocyte subpopulations in patients with carcinoma of the breast and uterine cervix

    International Nuclear Information System (INIS)

    Guha Thakurta, S.; De, M.; Roy Chowdhury, J.

    1983-01-01

    Immune competence was evaluated in 43 patients of carcinoma breast, 77 patients of cancer cervix, as compared to 30 normal healthy women. The study also included 25 women from the two carcinoma groups, who had undergone radiotherapy. A reduction in the white blood cell count, absolute lymphocyte count, active T-cell count and absolute T-cell count were observed in patients with carcinoma of the breast and cervix prior to irradiation. Radiation therapy resulted in a striking reduction of all the three parameters in both the carcinoma groups. Substantial recovery was observed within a year after cessation of therapy. Increased number of peripheral B lymphocytes was observed in carcinoma of the breast as well as the cervix prior to irradiation. At completion of radiation, the number decreased markedly in both groups of patients. Gradual recovery took place within a year. The reduction in lymphocyte numbers and its subpopulations could not be attributed to thymic irradiation, since patients receiving pelvic and mediastinal (including thymic) radiotherapy showed similar changes. (author)

  6. Peripheral lymphocyte subset variation predicts prostate cancer carbon ion radiotherapy outcomes

    Science.gov (United States)

    Shi, Ze-Liang; Li, Bing-Xin; Wu, Xian-Wei; Li, Ping; Zhang, Qing; Wei, Xun-Bin; Fu, Shen

    2016-01-01

    The immune system plays a complementary role in the cytotoxic activity of radiotherapy. Here, we examined changes in immune cell subsets after heavy ion therapy for prostate cancer. The lymphocyte counts were compared with acute radiotherapy-related toxicity, defined according to the Common Terminology Criteria for Adverse Events, and short-term local efficacy, defined based on prostate-specific antigen concentrations. Confirmed prostate cancer patients who had not received previous radiotherapy were administered carbon ion radiotherapy (CIR) in daily fractions of 2.74 GyE with a total dose of 63-66 GyE. Lymphocyte subset counts were investigated before, during and after radiotherapy, and at a 1 month follow-up. Most notable among our findings, the CD4/CD8 ratio and CD19+ cell counts were consistently higher in patients with a complete response (CR) or partial response (PR) to CIR than in those classified in the stable disease (SD) group (P<0.05 for both). But CD3+ and CD8+ cell counts were lower in the CR and PR groups than in the SD group. These results indicate that variations in peripheral lymphocyte subpopulations are predictive of outcome after CIR for prostate cancer. PMID:27029063

  7. Effect of IL-2 on recovery of proliferation ability of irradiated T lymphocytes

    International Nuclear Information System (INIS)

    Wang Ninghai; Zhang Lansheng

    1989-01-01

    3 H-thymidine incorporation assay was used to evaluated the proliferation ability of normal human peripheral blood T lymphocytes irradiated with or without exogenous IL-2 by 60 Co γ-ray at various doses after exposure to 1, 2.5, 5, 10, 20 and 40 Gy γ-ray, the DNA synthesis is blocked. It indicated IL-2 has damage effect on the proliferation ability of T cells. 3 H-thymidine incorporation rate in cells decreases with increasing dose of irradiation. Incorporation of 3 H-Tdk in irradiated groups in the dose range of 1 to 40 Gy was compared with that in the control group. The incorporation rate 3 H-TdR in these irradiated groups is 27 to 82 % of that in control group. The inhibition of lymphocyte proliferation was partially enhanced by adding IL-2, but the inhibiting effect on proliferation of human peripheral blood lymphocytes exposed to irradiation at more than 10 Gy is not reversible

  8. Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

    Science.gov (United States)

    Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

    2004-12-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

  9. Detection of radioiodine-induced cytogenetic alterations in circulating lymphocytes of thyroid patients

    Energy Technology Data Exchange (ETDEWEB)

    Kasuba, V [Inst. for Medical Recearch and Occupational Health, Zagreb (Croatia). Laboratory for Mutagenesis; Konrady, A; Koeteles, G J [Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary); Kusic, Z [Clinical Hospital Sestre Milosrdnice, Zagreb (Croatia). Dept. of Oncology and Nuclear Medicine

    1994-10-01

    Radioiodines are often used for experimental purposes and for diagnosis and therapy in clinical practice. Human population might also be exposed to radioiodines in nuclear accidents. The ionizing energy of radioiodine affects not only the thyroid where it concentrates but also other tissues, especially the lymphocytes during their circulation through and around the gland containing the radioisotopes. Therefore, it seemed to be of interest to carry out investigations concerning the cytogenetic alterations in blood lymphocytes of patients treated with iodine-131. The method of choice was the relatively easily performable micronucleus assay in cytokinesis-blocked cultures of human peripheral lymphocytes. The test was performed on blood samples of 30 patients before the radioisotope treatment and one, two and four days after, one as well as 6 and - in a few cases - 12 weeks later. The amounts of iodine-131 injected were dependent on the clinical practices to reach the therapeutic radiation doses for hyperthyroidism and adenomas and were in the range of 220 and 5180 MBq. it was observed that the micronucleus frequency increased in the treated hyperthyroid patients while in patients with toxic adenomas the radioiodine did not result in an increase or even as compared to the pretreatment values in a few cases decreased values were seen. The results suggest individual differences in radiosensitivity as well as that the frequency of cytogenetic alterations depend on the physiological or pathological conditions of the thyroid. The significance of this observation will be discussed for dose assessments by cytogenetic techniques due to internal radioiodine. (author).

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

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

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

  11. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT from Growing Wistar Rats

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    Gustavo A. Sosa

    2004-01-01

    Full Text Available The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1 the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2 that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+, were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats.

  12. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

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    Zana, Marianna; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Szabo, Krisztina; Vetro, Agnes; Szucs, Peter; Varkonyi, Agnes; Pakaski, Magdolna; Boda, Krisztina; Rasko, Istvan; Janka, Zoltan; Kalman, Janos

    2006-01-01

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults

  13. Effect of Smoking on Peripheral Blood Lymphocyte Subsets of Patients With Chronic Renal Failure.

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    Düvenci Birben, Özlem; Akçay, Şule; Sezer, Siren; Şirvan, Şale; Haberal, Mehmet

    2016-11-01

    Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.

  14. Cytological and cytochemical effects of sodium benzoate and gamma irradiation on human peripheral lymphocytes

    International Nuclear Information System (INIS)

    Mohamed, N.A.F.

    1981-01-01

    In vitro studies of human peripheral lymphocytes were conducted to elucidate and compare the effects of a suspected chemical clastogen, sodium benzoate, widely used in the food industry as an antimicrobial food additive, to that of a well-known physical mutagen, gamma rays. Blood from ten normal donors, five males and five females, was collected and treated with various doses of the two agents independently and in combination during G 0 or G 1 phase. Induction of structural chromosomal aberrations, sister chromatid exchanges (SCEs) and unscheduled DNA synthesis were used as parameters to monitor the effects of the two agents. Sodium benzoate at the same concentrations used in the food industry (0.05% and 0.10%) caused inhibition of mitosis and induced chromatid-type aberrations (gaps and breaks). The frequency of aberrations increased as the concentration of sodium benzoate increased. No increase in SCEs over the control level was observed as either concentration tested. The relative amount of DNA damage inflicted in the treated lymphocytes estimated as 3 H-tritiated thymidine incorporation (unscheduled DNA synthesis) was highly significant. In contrast, blood irradiated with 300, 600, or 900 rad 60 Co gamma rays produced chromatid and chromosome aberrations in cultured lymphocytes, dicentrics being the most frequent exchange event. The aberration yield was found to be dose-dependent and to fit the quadratic model. Unscheduled DNA synthesis as measured by lymphocyte 3 H-TdR incorporation following gamma irradiation was highly significantly increased with the largest uptake occurring during the first hour of incubation. The combined treatment of gamma irradiation plus 0.05% sodium benzoate did not increase the aberration frequencies over the independent irradiation treatments and had no effect on SCEs frequencies

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

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    H Keshavarz

    2008-12-01

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

  16. Ibrutinib for treatment of chronic lymphocytic leukemia.

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    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.

  17. Current Treatment of Chronic Lymphocytic Leukemia.

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    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.

  18. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

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    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.

     

  19. The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

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    Pedro Xavier-Elsas

    2015-01-01

    Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

  20. Correlation between the neutrophil-lymphocyte count ratio and bacterial infection in patient with human immunodeficiency virus

    Science.gov (United States)

    Kusnadi, D.; Liwang, M. N. I.; Katu, S.; Mubin, A. H.; Halim, R.

    2018-03-01

    Parameters for starting antibiotic therapy such as CRP andleukocytosis are considered non-specific. Previous studies have shown the Neutrophil-Lymphocyte Count Ratio (NLCR) can serve as the basis of bacterial infection, the level of infection, and the basis of antibiotic therapy. Compared with the Procalcitonin parameter, this NLCR is rapid, an inexpensive and requires no additional sampling. To determine the correlation between The Neutrophil-LymphocyteCount Ratio to bacterial infection in HIV patients. This study was a cross-sectional observational approach to HIV subject at Wahidin Sudirohusodo and Hasanuddin University Hospital. The subjects performed routine blood, microbiology test,and blood Procalcitonin levels tests. Then performed NLCR calculations based on routine blood results. The subjects then grouped the presence or absence of bacterial infection.In 146 study subjects, there were 78 (53.4%) with bacterial infections and 68 (46.6%) without bacterial infection as controls. Subjects with bacterial infections had higher total neutrophils (84.83) compared with non-bacterial infections. Subjects with bacterial infections had total lymphocytes with an average of 8.51 lower than non-bacterial infections. Subjects with bacterial infections had higher NLCR values with an average of 12.80. The Neutrophil-Lymphocyte Count Ratio can become a marker of bacterial infection in HIV patients.

  1. Development of a serum-free medium for in vitro expansion of human cytotoxic T lymphocytes using a statistical design

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    Lee Gyun

    2010-09-01

    Full Text Available Abstract Background Serum-containing medium (SCM, which has a number of poorly defined components with varying concentrations, hampers standardization of lymphocyte cultures. In order to develop a serum-free medium (SFM for the expansion of human lymphocytes from peripheral blood mononuclear cells (PBMCs, a statistical optimization approach based on a fractional factorial method and a response surface method was adopted. A basal medium was prepared by supplementing RPMI1640 medium with insulin, albumin, ferric citrate, ethanolamine, fatty acids, glutamine, sodium pyruvate, 2-mercaptoethanol, 1-thioglycerol, nonessential amino acids, and vitamins. We identified additional positive determinants and their optimal concentrations for cell growth through a statistical analysis. Results From a statistical analysis using the fractional factorial method, cholesterol and polyamine supplement were identified as positive determinants for cell growth. Their optimal concentrations were determined by the response surface method. The maximum viable cell concentration in the developed SFM was enhanced by more than 1.5-fold when compared to that in RPMI1640 supplemented with 10% fetal bovine serum (FBS. Furthermore, a cytotoxicity assay and an enzyme-linked immunospot assay revealed that the effector function of cytotoxic T lymphocytes generated from PBMCs grown in SFM, by stimulation of peptide-presenting dendritic cells, was retained or even better than that in SCM. Conclusions The use of a developed SFM with cholesterol and polyamine supplement for human lymphocyte culture resulted in better growth without loss of cellular function when compared to SCM.

  2. Development of a serum-free medium for in vitro expansion of human cytotoxic T lymphocytes using a statistical design.

    Science.gov (United States)

    Jeon, Min Kyoung; Lim, Jong-Baeck; Lee, Gyun Min

    2010-09-21

    Serum-containing medium (SCM), which has a number of poorly defined components with varying concentrations, hampers standardization of lymphocyte cultures. In order to develop a serum-free medium (SFM) for the expansion of human lymphocytes from peripheral blood mononuclear cells (PBMCs), a statistical optimization approach based on a fractional factorial method and a response surface method was adopted. A basal medium was prepared by supplementing RPMI1640 medium with insulin, albumin, ferric citrate, ethanolamine, fatty acids, glutamine, sodium pyruvate, 2-mercaptoethanol, 1-thioglycerol, nonessential amino acids, and vitamins. We identified additional positive determinants and their optimal concentrations for cell growth through a statistical analysis. From a statistical analysis using the fractional factorial method, cholesterol and polyamine supplement were identified as positive determinants for cell growth. Their optimal concentrations were determined by the response surface method. The maximum viable cell concentration in the developed SFM was enhanced by more than 1.5-fold when compared to that in RPMI1640 supplemented with 10% fetal bovine serum (FBS). Furthermore, a cytotoxicity assay and an enzyme-linked immunospot assay revealed that the effector function of cytotoxic T lymphocytes generated from PBMCs grown in SFM, by stimulation of peptide-presenting dendritic cells, was retained or even better than that in SCM. The use of a developed SFM with cholesterol and polyamine supplement for human lymphocyte culture resulted in better growth without loss of cellular function when compared to SCM.

  3. Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT in the chicken

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    McNulty John A

    2006-01-01

    Full Text Available Abstract Background Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle. Results PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80% with the remaining 20% comprising B-cells and monocytes (Bu-1+, which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75–80%, CD8+ (20–25%, TCRαβ/Vβ1+ (60%, and TCRγδ+ (15%. All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRαβ/Vβ1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h compared to the dark:light interphase (0700 h. Conclusion The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light

  4. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine

    International Nuclear Information System (INIS)

    Gudzenko, N.; Hatch, M.; Bazyka, D.; Dyagil, I.; Reiss, R.F.; Brenner, A.; Chumak, V.; Babkina, N.; Zablotska, L.B.; Mabuchi, K.

    2015-01-01

    Background: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. Methods: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. Results: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. Conclusions: These data – the first from a working population in Ukraine – add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. - Highlights: • A unique population – a cohort of 110,645 Chernobyl clean-up workers from Ukraine. • Followed 1986–2006 for leukemia, interviewed about non-radiation risk factors. • Petroleum exposure increased risk for non-CLL leukemias, particularly CML. • No risk factor other than radiation was found for CLL.

  5. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine

    Energy Technology Data Exchange (ETDEWEB)

    Gudzenko, N., E-mail: gudznat@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Hatch, M., E-mail: hatchm@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Bazyka, D., E-mail: Bazyka@yahoo.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Dyagil, I., E-mail: leuk@ukr.net [National Research Center for Radiation Medicine, Kyiv (Ukraine); Reiss, R.F., E-mail: rfr1@columbia.edu [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Brenner, A., E-mail: brennera@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Chumak, V., E-mail: Chumak.vadim@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Babkina, N., E-mail: natalie.babkina@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Zablotska, L.B., E-mail: lydia.zablotska@ucsf.edu [Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA (United States); Mabuchi, K., E-mail: mabuchik@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States)

    2015-10-15

    Background: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. Methods: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. Results: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. Conclusions: These data – the first from a working population in Ukraine – add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. - Highlights: • A unique population – a cohort of 110,645 Chernobyl clean-up workers from Ukraine. • Followed 1986–2006 for leukemia, interviewed about non-radiation risk factors. • Petroleum exposure increased risk for non-CLL leukemias, particularly CML. • No risk factor other than radiation was found for CLL.

  6. Signalling detection of DNA damage induced by low doses of ionizing radiation in human lymphocytes

    International Nuclear Information System (INIS)

    Valente, M.

    2011-01-01

    gamma-H2AX foci in response to irradiation. Using the methodological tools developed during this thesis we established for the various lymphocyte subsets the relationship between radiation dose and gamma-H2AX foci frequency as well as the kinetics of appearance/disappearance of gamma-H2AX foci. Finally, since no additional samples from patients of known radiosensitivity were available to continue the initial study with the improved protocol, we focused on radiosensitivity in another context: radio-adaptive response. This phenomenon corresponds to a lower cellular response to high dose of ionizing radiation exposure if it is preceded by an exposure to low doses. With the conditions used here we did not observe a radio-adaptive response in terms of gamma-H2AX signalling regardless of the lymphocyte subpopulation studied. However, the translocation rate of pre-irradiated CD4-positive lymphocytes was significantly different when compared to cells only irradiated acutely. This result thus indicates a differential repair of double strand breaks in lymphocytes after a radio-adaptation. (author)

  7. 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)

  8. 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.

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

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    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.

  10. 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

  11. Evaluation of Neutrophil–Lymphocyte Ratio, Platelet–Lymphocyte Ratio and Red Blood Cell Distribution Width–Platelet Ratio for Diagnosis of Premature Ovarian Insufficiency

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    Gülşah Ilhan

    2017-03-01

    Full Text Available Objective: To evaluate whether systemic inflammatory markers (neutrophil to lymphocyte ratio (NLR, platelet to lymphocyte ratio (PLR and red blood cell distribution width (RDW to platelet ratio (RPR can be used as reliable markers for the diagnosis of premature ovarian insufficiency (POI and to determine if there is a relationship between these markers and follicle stimulating hormone (FSH, Anti-Müllerian Hormone (AMH levels.Materials and methods: Written and electronic medical records were reviewed using searches for diagnoses with the terms of 'premature ovarian failure', 'premature ovarian insufficiency'. Patients younger than the age of 40 were diagnosed to have premature ovarian insufficiency based on their menstrual history and sonographic examination and they were compared with healthy females. Complete blood counts, day-3 hormone profiles, AMH levels of all subjects were analyzed.Results: NLR was statistically higher in POI group compared with controls (p < 0.05. NLR had a positive correlation between FSH (r = 0.23, p = 0.045 and a negative association with AMH (r = - 0.27, p = 0.018. The area under ROC curve for NLR in POI was 0.66, with a threshold value 1.5 and sensitivity = 75.7 % and specificity = 46.0 %.Conclusion: NLR can be a marker for the diagnosis of POI. There is a close relationship between NLR and ovarian reserve markers such as FSH and AMH.

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

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    Tonney S Nyirenda

    2010-10-01

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

  13. The Predictive Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio for the Effusion Viscosity in Otitis Media With Chronic Effusion.

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    Elbistanli, Mustafa Suphi; Koçak, Hasan Emre; Acipayam, Harun; Yiğider, Ayşe Pelin; Keskin, Mehmet; Kayhan, Fatma Tülin

    2017-05-01

    The objective of the authors' study was to investigate the predictive value of the neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) in otitis media with effusion and the correlation of the effusion type with these ratios. Retrospective case-control study. One hundred twenty-six pediatric patients diagnosed otitis media with chronic effusion and had ventilation tube inserted between October 2015 and July 2016 were included in the study group and 124 healthy children, who applied for the routine examination and had blood count analysis, were included in the control group. The patients in the study group were divided into 2 groups regarding the effusion viscosity, which was obtained from the patients' operation files. Seventy-one patients were included in the serous group and 55 patients in the mucous group. The NLR and PLR rates of the groups were compared and statistically evaluated. The average NLR and PLR rates were significantly higher in the study group than in the control group (P = 0.000, P = 0.004 respectively). Comparison of the serous and mucous groups with the control group revealed a significant difference between the control group and the serous group regarding the NLR and PLR (P = 0.000; P = 0.000 respectively), but not between the control group and mucous group (P = 0.694; P = 0.691 respectively). Neutrophil-lymphocyte rate and PLR had a predictive value for otitis media with effusion and additionally it was a laboratory indicator supporting the typing of the viscosity of the fluid accumulated in the middle ear.

  14. 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.

  15. Lymphocytic Panhypophysitis: Its Clinical Features in Japanese Cases

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    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.

  16. 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.)

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

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    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.

  18. Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine

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    Mandrik O

    2015-08-01

    Full Text Available Olena Mandrik,1 Isaac Corro Ramos,2 Saskia Knies,1,3 Maiwenn Al,1,2 Johan L Severens1,2 1Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute of Medical Technology Assessment (iMTA, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3National Health Care Institute, Diemen, the Netherlands Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER

  19. Expression of Lymphocyte-derived Growth Hormone (GH) and GH-releasing Hormone Receptors in Aging Rats

    OpenAIRE

    Weigent, Douglas A.

    2013-01-01

    In the present study, we show that higher levels of lymphocyte GH are expressed in spleen cells from aging animals compared to young animals. Further, leukocytes from primary and secondary immune tissues and splenic T and B cells from aging rats all express higher levels of GHRH receptors compared to younger animals. Bone marrow and splenic T cells express the highest levels of GHRH receptor in aging animals. Spleen cells from aging animals showed no significant change in proliferation or GH ...

  20. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

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    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.

  1. Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib.

    Science.gov (United States)

    Ivanova, Donika; Zhelev, Zhivko; Lazarova, Dessislava; Getsov, Plamen; Bakalova, Rumiana; Aoki, Ichio

    2018-03-01

    Recent studies provided convincing evidence for the anticancer activity of combined application of vitamin C and pro-vitamin K3 (menadione). The molecular pathways underlying this process are still not well established. The present study aimed to investigate the effect of the combination of vitamin C plus pro-vitamin K3 on the redox status of leukemia and normal lymphocytes, as well as their sensitizing effect for a variety of anticancer drugs. Cytotoxicity of the substances was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by fluorescein isothiocyanate-annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen and nitrogen species and protein-carbonyl products. Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%, but did not influence the viability of normal lymphocytes. All combinations of anticancer drug plus vitamins C and K3 were characterized by synergistic cytotoxicity towards Jurkat cells, compared to cells treated with drug alone for 24 h. In the case of barasertib and everolimus, this synergistic cytotoxicity increased within 72 hours. It was accompanied by strong induction of apoptosis, but a reduction of level of hydroperoxides and moderately increased protein-carbonyl products in leukemia cells. Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes. The combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. 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.

  3. 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

  4. 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

  5. The ibrutinib B-cell proliferation inhibition is potentiated in vitro by dexamethasone: Application to chronic lymphocytic leukemia.

    Science.gov (United States)

    Manzoni, Delphine; Catallo, Régine; Chebel, Amel; Baseggio, Lucile; Michallet, Anne-Sophie; Roualdes, Olivier; Magaud, Jean-Pierre; Salles, Gilles; Ffrench, Martine

    2016-08-01

    New B-cell receptor-targeted therapies such as ibrutinib, a Bruton tyrosine kinase inhibitor, are now proposed for lymphoid pathologies. The putative benefits of its combination with glucocorticoids were evaluated here. We compared the effects of dexamethasone (DXM), ibrutinib and their in vitro combination on proliferation and metabolic stress markers in stimulated normal B-lymphocytes and in malignant lymphocytes from chronic lymphocytic leukemia (CLL) patients. In both cellular models, cell cycle progression was globally inhibited by DXM and/or ibrutinib. This inhibition was significantly amplified by DXM addition to ibrutinib and was related to a significant decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E. Apoptosis increased especially with DXM/ibrutinib combination and was associated with a significant decrease in Mcl-1 expression. Treatment effects on metabolic stress were evaluated by DNA damage recognition after 53BP1 foci labeling. The percentage of cells with more than five 53BP1 foci decreased significantly with ibrutinib in normal and CLL lymphocytes. This decrease was strongly reinforced, in CLL, by DXM addition. Our data indicated that, in vitro, DXM potentiated antiproliferative effects of ibrutinib and decreased DNA damage in lymphoid B-cells. Thus their combination may be proposed for CLL treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Effect Of SEA On Long Tail Monkeys (Macaca Fascicularis) Lymphocyte Culture Gamma Ray-Irradiated In Vitro

    International Nuclear Information System (INIS)

    Wa'id, Abdul; Lusiyanti, Yanti

    2000-01-01

    Staphylococus enteroxine (SEA) is one of toxins produced by the bacterium Staphylococus aureus. In the culture, SEA has proven as a potent stimulator of lymphocytes in man event at fg/ml concentrations. This research studied the effect of SEA compared to Phytohaemagglutinine (PHA) on the peripheral blood lymphocytes culture of the long-tail monkeys. About 5 ml blood was collected from 5 monkeys and irradiated using Gamma Cell-220 P3TIR with doses of 0 (control); 1.0; 2.0; 3.0 and 4.0 Gy. The blood samples were cultured in the appropriate growth medium based on standard procedure and added with 1.0 ml (0.5 mug/ml) SEA or 0.15 ml PHA. The cultures were then incubated for 96 hours and prepared the slides. The results showed that on the unirradiated peripheral blood lymphocytes of long-tail monkeys the mitotic indices obtained using PHA and SEA are relatively similar. On the irradiated lymphocytes with doses of 1-3 Gy, the mitotic indices using SEA are relatively higher than that of PHA. Dose responses of dicentric, ring and acentric fragment of both PHA and SEA are relatively the same

  7. Intestinal IgA responses to Giardia muris in mice depleted of helper T lymphocytes and in immunocompetent mice.

    Science.gov (United States)

    Heyworth, M F

    1989-04-01

    Immunocompetent mice infected with Giardia muris generate an intestinal antibody response to this parasite and clear G. muris infection. Previous work has shown that G. muris infection is prolonged in mice that have been depleted of helper (CD4+) T lymphocytes by treatment with a monoclonal antibody (mAb) directed against the murine CD4 antigen. The aim of the present study was to compare the intestinal anti-Giardia antibody response in immunocompetent mice and in mice depleted of helper T (Th) lymphocytes by treatment with anti-CD4 mAb. Immunocompetent mice generated an IgA response to G. muris, as judged by the presence of IgA on Giardia trophozoites harvested from the intestine of these animals more than 10 days after the start of the infection. The anti-Giardia IgA response was impaired in mice depleted of Th lymphocytes, as judged by virtual absence of immunofluorescent staining of trophozoites from these animals for surface-bound IgA. Clearance of G. muris infection was impaired by treatment of mice with anti-CD4 mAb. The results suggest that Th (CD4+) lymphocytes are important for the generation of a local IgA response against G. muris trophozoites in the mouse intestine and that IgA anti-trophozoite antibody may contribute to the clearance of G. muris from the intestine of immunocompetent mice.

  8. Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

    Science.gov (United States)

    Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

    2014-03-01

    The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

  9. FREQUENCY OF CHROMOSOMAL ABERRATIONS AND MICRONUCLEI IN HORSE LYMPHOCYTES FOLLOWING IN VITRO EXPOSURE TO LOW DOSE IONISING RADIATION

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    Dunja Rukavina

    2012-07-01

    Full Text Available Ionising radiation is known to cause chromosomal instability, which is observed as increased frequency of chromosomal aberration and micronuclei. These are listed as reliable criteria in biological dosimetry. Numerous experiments conducted on both animal and plant models demonstrated that increase in radiation dosage is followed by increased mutation frequency, and that mutations occur even at the lowest exposure. We used horse blood in vitro irradiated by low doses of ionizing radiation. Cultivation of peripheral blood lymphocytes and micronucleus test were used as biomarkers of genetic damage. The observed aberrations were recorded and classified in accordance with the International System of Cytogenetic Nomenclature. Micronuclei were identified on the basis of criteria proposed by Fenech et al. (8. Analysis of chromosomal aberration showed increased frequency of aberrations in blood cultures exposed to 0,1 Gy and 0,2 Gy compared to the controls. Microscopic analysis of chromosomal damage in in vitro micronucleus test revealed that the applied radiation dose induced micronuclei while no binucleated cells with micronuclei were found in lymphocytes that were not irradiated. In this paper we analysed the influence of low dose ionising radiation on frequency of chromosomal aberration and micronuclei in horse lymphocytes following in vitro exposure to X-rays (0,1 Gy and 0,2 Gy. Key words: chromosomal aberrations, micronuclei, ionising radiation, horse lymphocytes

  10. Impact of the New Generation Reconstituted Surfactant CHF5633 on Human CD4+ Lymphocytes.

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    Markus Fehrholz

    Full Text Available Natural surfactant preparations, commonly isolated from porcine or bovine lungs, are used to treat respiratory distress syndrome in preterm infants. Besides biophysical effectiveness, several studies have documented additional immunomodulatory properties. Within the near future, synthetic surfactant preparations may be a promising alternative. CHF5633 is a new generation reconstituted synthetic surfactant preparation with defined composition, containing dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylglycerol and synthetic analogs of surfactant protein (SP- B and SP-C. While its biophysical effectiveness has been demonstrated in vitro and in vivo, possible immunomodulatory abilities are currently unknown.The aim of the current study was to define a potential impact of CHF5633 and its single components on pro- and anti-inflammatory cytokine responses in human CD4+ lymphocytes.Purified human CD4+ T cells were activated using anti CD3/CD28 antibodies and exposed to CHF5633, its components, or to the well-known animal-derived surfactant Poractant alfa (Curosurf®. Proliferative response and cell viability were assessed using flow cytometry and a methylthiazolyldiphenyltetrazolium bromide colorimetric assay. The mRNA expression of IFNγ, IL-2, IL-17A, IL-22, IL-4, and IL-10 was measured by quantitative PCR, while intracellular protein expression was assessed by means of flow cytometry.Neither CHF5633 nor any of its phospholipid components with or without SP-B or SP-C analogs had any influence on proliferative ability and viability of CD4+ lymphocytes under the given conditions. IFNγ, IL-2, IL-17A, IL-22, IL-4, and IL-10 mRNA as well as IFNγ, IL-2, IL-4 and IL-10 protein levels were unaffected in both non-activated and activated CD4+ lymphocytes after exposure to CHF5633 or its constituents compared to non-exposed controls. However, in comparison to Curosurf®, expression levels of anti-inflammatory IL-4 and IL-10 mRNA were

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

    Directory of Open Access Journals (Sweden)

    Jun LUO

    2011-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

  17. 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...

  18. 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

  19. Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Pukkala Eero

    2010-06-01

    Full Text Available Abstract Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML, acute lymphocytic leukemia (ALL, chronic lymphocytic leukemia (CLL, and chronic myeloid leukemia (CML. Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size. Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57, but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003. The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17. Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39 for low ( 100 ppm-years. In a meta-regression, the trend was statistically significant (P = 0.015. Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95, medium (2.32, 95% CI, 0.91-5.94 to high exposure category (3.20, 95% CI, 1.09-9.45, but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an

  20. No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Vasan, Senthil K

    2015-01-01

    Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL...... of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries' entire computerized...

  1. Sister chromatid exchanges and micronuclei analysis in lymphocytes of men exposed to simazine through drinking water.

    Science.gov (United States)

    Suárez, Susanna; Rubio, Arantxa; Sueiro, Rosa Ana; Garrido, Joaquín

    2003-06-06

    In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.

  2. Are neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as effective as Fournier's gangrene severity index for predicting the number of debridements in Fourner's gangrene?

    Science.gov (United States)

    Kahramanca, Sahin; Kaya, Oskay; Özgehan, Gülay; Irem, Burak; Dural, Ibrahim; Küçükpınar, Tevfik; Kargıcı, Hülagü

    2014-03-01

    Fournier's gangrene (FG) is a rapidly progressive and necrotizing infection of the subcutaneous and fascial tissues with a high mortality rate. In the present study, we aimed to investigate prognostic factors and analyze the outcomes of 68 patients in a tertiary reference hospital. Patients admitted to the emergency department were investigated retrospectively between January 2006 and January 2013 and divided into two groups. The patients in Group I (G1) required one debridement, and Group II (G2) patients required more than one. Patient demographic and clinical characteristics were encoded. Fournier's Gangrene Severity Index (FGSI) scores, neutrophil-lymphocyte ratios (NLR), and platelet-lymphocyte ratios (PLR) were calculated. Prognostic factors were compared between the groups. There were no statistically significant differences between the groups in terms of mean age, female-male ratio, or duration of symptoms on admission; however, there were more infection sources, predisposal factors, and positive culture results in G2. Additionally, hospital stay, total cost, and mortality rate values were high in G2. We found statistically higher NLR and PLR ratios in G2, but there was no significant difference in FGSI scores between the groups. The FGSI scoring system was not found to be valuable in determining prognosis. However, NLR and PLR were valuable, and previous use of NLR and PLR for determining Fournier's gangrene prognosis could not be found in the English literature.

  3. Assessment of neutrophil / lymphocyte ratio in patients with myocardial bridge

    Directory of Open Access Journals (Sweden)

    Abdulkadir Yıldız

    2014-03-01

    Full Text Available Objective: Myocardial bridge (MB is a congenital anomaly characterized by systolic narrowing of the epicardial coronary arterial segment while traveling in the myocardium. It is a benign entity but previous studies showed that the proximal portion is prone to an enhanced atherosclerosis. Neutrophil/lymphocyte ratio (NLR is a sensitive marker of systemic inflammation used as a predictor for adverse cardiovascular outcomes in atherosclerotic heart disease. So in this study, we sought to evaluate the association between NLR and myocardial bridging. Methods: A total of 172 patients (mean age: 50.8 ± 11.5 years, 77.3% men with either angiographically proven MB or normal coronary arteries were included in the study. For the entire study population, hematologic parameters were measured using an automatic blood counter. Results: The study population consisted of 71 patients with MB (mean age: 51.4 ± 11.9 years, 80.3% male and 101 patients with normal coronary arteries (mean age: 50.5 ± 11.3 years, 75.2% male. There were no significant differences between groups regarding hemoglobin level, platelet count, glucose and creatinine. Compared to the control group, NLR was significantly higher in patients with MB (2.45 ± 1.19 vs. 1.72 ± 0.48; p 1.82 predicted myocardial bridge presence with 70% sensitivity and 71% specificity (ROC area under curve: 0.733, 95% CI: 0.654-0.811, p < 0.001. Conclusion: Our study findings demonstrated that MB is associated with elevated NLR, which is used to assess inflammatory status of the body. J Clin Exp Invest 2014; 5 (1: 24-28

  4. 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

  5. Resident Macrophages and Lymphocytes in the Canine Endometrium.

    Science.gov (United States)

    Pires, M A; Payan-Carreira, R

    2015-10-01

    Resident immune cells play a major role in endometrial immunity and in tissue homoeostasis. This study aimed to analyse the distribution of macrophages, B and T lymphocytes (respectively, Mø, B-Lym and T-Lym) in the canine endometrium throughout the oestrous cycle and in late involution (at the proestrus stage post-parturition). An immunohistochemistry technique was used on samples from 50 post-pubertal healthy female dogs, of which five in late post-partum. The distribution of resident immune cells was analysed in three endometrial layers (superficial, intermediate and basal areas). Mø, B-Lym and T-Lym were demonstrated to reside in the endometrium in all the stages of the canine cycle; their numbers being considerably higher during late involution. T-Lym were scattered in the stroma or amidst the glandular epithelium, constituting the predominant immune cell population in anestrus and proestrus, but decreased in number at all other stages. Endometrial B-Lym remained fairly constant during the canine cycle, although its numbers were higher in late involution. Mø counts were higher during anestrus compared to the other stages, the cells being displaced into the superficial endometrial layer. Mø demonstrated the highest level in late involution samples, forming small aggregates below the surface epithelium. The number of immune cells was not normally distributed, suggesting the influence of individual factors, such as age or parity, not explored herein due to limited sample availability. Still, this study provides important information for the interpretation of endometrial biopsies in dogs and for the understanding of the increased susceptibility to uterine infection during dioestrus found in the bitch. © 2015 Blackwell Verlag GmbH.

  6. DNA double-strand break and apoptosis induction in human lymphocytes in different cycle cell phases by 60Co gamma rays and Bragg peak protons of a medical beam

    International Nuclear Information System (INIS)

    Khachenkova, A.A.; Boreyko, A.V.; Mozhaeva, A.V.; Chausov, V.N.; Ravnachka, I.I.; Amov, I.; Tiunchik, S.I.

    2009-01-01

    A comparative analysis is made of the regularities in the formation of DNA double-strand break and apoptosis induction in peripheral human blood lymphocytes in different cell cycle phases after 60 Co gamma and extended Bragg peak proton irradiation. It is shown that the formation of apoptotic cells in a lymphocyte population increases linearly in all the cell cycle stages after proton irradiation. The maximal DNA double-strand break and apoptosis yield in lymphocytes is observed in the S phase of the cell cycle

  7. 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

  8. 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.

  9. 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

  10. Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

    International Nuclear Information System (INIS)

    Estrela-Lima, Alessandra; Araújo, Márcio SS; Costa-Neto, João M; Teixeira-Carvalho, Andréa; Barrouin-Melo, Stella M; Cardoso, Sergio V; Martins-Filho, Olindo A; Serakides, Rogéria; Cassali, Geovanni D

    2010-01-01

    The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry. Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4 + (≥ 66.7%) or CD8 + T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity ≥ 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4 + T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8 + T-cells was higher in MC-BMT without

  11. Sensitive DNA impedance biosensor for detection of cancer, chronic lymphocytic leukemia, based on gold nanoparticles/gold modified electrode

    International Nuclear Information System (INIS)

    Ensafi, Ali A.; Taei, M.; Rahmani, H.R.; Khayamian, T.

    2011-01-01

    Highlights: → Chronic lymphocytic leukemia causes an increase in the number of white blood cells. → We introduced a highly sensitive biosensor for the detection of chronic lymphocytic leukemia. → A suitable 25-mer ssDNA probe was immobilized on the surface of the gold nanoparticles. → We used electrochemical impedance spectroscopy as a suitable tool for the detection. → Detection of chronic lymphocytic leukemia in blood sample was checked using the sensor. - Abstract: A simple and sensitive DNA impedance sensor was prepared for the detection of chronic lymphocytic leukemia. The DNA electrochemical biosensor is worked based on the electrochemical impedance spectroscopic (EIS) detection of the sequence-specific DNA related to chronic lymphocytic leukemia. The ssDNA probe was immobilized on the surface of the gold nanoparticles. Compared to the bare gold electrode, the gold nanoparticles-modified electrode could improve the density of the probe DNA attachment and hence the sensitivity of the DNA sensor greatly. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy were performed in a solution containing 1.0 mmol L -1 K 3 [Fe(CN) 6 ]/K 4 [Fe(CN) 6 ] and 50 mmol L -1 phosphate buffer saline pH 6.87 plus 50 mmol L -1 KCl. In the CV studied, the potential was cycled from 0.0 to +0.65 V with a scan rate of 50 mV s -1 . Using EIS, the difference of the electron transfer resistance (ΔR et ) was linear with the logarithm of the complementary oligonucleotides sequence concentrations in the range of 7.0 x 10 -12 -2.0 x 10 -7 mol L -1 , with a detection limit of 1.0 x 10 -12 mol L -1 . In addition, the DNA sensor showed a good reproducibility and stability during repeated regeneration and hybridization cycles.

  12. Old beagle dogs have lower faecal concentrations of some fermentation products and lower peripheral lymphocyte counts than young adult beagles.

    Science.gov (United States)

    Gomes, Márcia de Oliveira Sampaio; Beraldo, Mariana Casteleti; Putarov, Thaila Cristina; Brunetto, Márcio Antônio; Zaine, Leandro; Glória, Maria Beatriz Abreu; Carciofi, Aulus Cavalieri

    2011-10-01

    The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 × 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15 d adaptation period preceded a 5 d total collection of faeces for the digestibility trial. On day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0.15, 0.30 and 0.45 % of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P 0.15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P ≤ 0.05) and faecal pH was higher (P = 0.03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P ≤ 0.01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

  13. 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...

  14. 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...

  15. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  16. The prognostic value of lymphocyte-to-monocyte ratio in retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Yu-Xiang Hu

    2017-11-01

    Full Text Available AIM: To evaluate the associations between development of retinopathy of prematurity (ROP and serum lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR. METHODS: A retrospective cohort study was performed, involving infants who were screened for ROP from January 2015 to December 2015. Preterm newborns of ≤32 gestational weeks with ROP were enrolled as the observation group, and non-ROP infants were enrolled as the control group, whose complete blood cell were measured within the first 24h of life. The levels of NLR, LMR and PLR were determined in all groups. The data obtained were analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, 40 cases of ROP were enrolled and 40 cases of non-ROP as controls. The LMR levels were significantly higher (P<0.001 in ROP group (3.96±1.16 compared to non-ROP group (2.85±0.79. The NLR levels were significantly lower (P=0.035 in ROP group {median [interquartile range (IQR], 0.88 (0.67-1.46} compared to non-ROP group [median (IQR, 1.20 (0.85-1.89]. The median PLR values were 61.99 (IQR, 50.23-75.98 in ROP group and 69.24 (IQR, 55.52-88.12 in non-ROP group (P=0.104. Logistic regression analysis suggested that LMR was an independent risk factor for ROP (OR: 0.275; 95% CI: 0.134-0.564; P=0.001. CONCLUSION: The findings demonstrate that higher LMR is independently and significantly associated with the development of ROP, and the LMR may be invoked as a predictive tool for identifying risk for ROP.

  17. Effects of acupuncture on peripheral T lymphocyte subpopulation and amounts of cerebral catecholamines in mice.

    Science.gov (United States)

    Okumura, M; Toriizuka, K; Iijima, K; Haruyama, K; Ishino, S; Cyong, J C

    1999-01-01

    The aim of this study was to investigate the effects of acupuncture on peripheral lymphocyte subpopulations and cerebral catecholamines. In order to examine the effects of acupuncture, two experiments were performed. Experiment 1: Eighteen female mice (strain; C57BL/6) at the age of 7 weeks were divided three groups, (a) sham operated (control; n=6), (b) ovariectomized (OVX; n=6), and (c) ovariectomized and stimulated by subcutaneous needles on acupuncture point, Shenshu (BL23) at the both sides of the back for 20 days (OVX+Acu; n=6). These animals were sacrificed at 20 days after needle insertion, and the splenic lymphoid cells were examined by two-color flow cytometry, using monoclonal antibodies (mAb) to the cell surface antigens, CD3, CD4, CD8a and NK1.1 (CD56). In the ovariectomized (OVX) group, the peripheral CD4/CD8 ratio was significantly increased and the ratio of natural killer (NK) cells (CD3-NK1.1+; CD3 negative, NK1.1 positive) to T lymphocytes was decreased compared to the sham control group. In the ovariectomized with needle insertion (OVX+Acu) group, the CD4/CD8 ratio was reduced, but the NK cells ratio was not changed compared to the OVX group. Experiment 2: To investigate the acute effects of subcutaneous needle insertion, male C57BL/6 mice (7 weeks old) were used (n=6, each group). The acupuncture points Shen-shu (BL23) on the backs of the male mice were also stimulated by subcutaneous needles for 3 and 7 days. As a result, the CD4/CD8 ratio was significantly decreased at day 3 and day 7, compared to the control group. On the other hand the NK cells ratio and activated T-cells were increased at day 7. The mitogenic activities in the splenic lymphocytes were also increased by acupuncture stimulation at day 3. Catecholamine contents in the hippocampus were measured by high performance liquid chromatography with the electro-chemical detector (ECD-HPLC) method. No significant change was observed in either dopamine contents or norepinephrine; however

  18. Efficacy of DSP30-IL2/TPA for detection of cytogenetic abnormalities in chronic lymphocytic leukaemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Holmes, P J; Peiper, S C; Uppal, G K; Gong, J Z; Wang, Z-X; Bajaj, R

    2016-10-01

    Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set-up: unstimulated, DSP30/IL-2-stimulated and TPA-stimulated. In 2012-2013, two cultures were set-up: unstimulated and stimulated with TPA/DSP30/IL-2. In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012-2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL-2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012-2013. The TPA/DSP30/IL-2 cultures in 2012-2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL-2 alone (n = 3). TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL-2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities. © 2016 John Wiley & Sons Ltd.

  19. Predictors of change in CD4 lymphocyte count and weight among HIV infected patients on anti-retroviral treatment in Ethiopia: a retrospective longitudinal study.

    Directory of Open Access Journals (Sweden)

    Ayalu A Reda

    Full Text Available Antiretroviral treatment (ART has been introduced in Ethiopia a decade ago and continues to be scaled up. However, there is dearth of literature on the impact of ART on changes in CD4 lymphocyte count and weight among patients on treatment.To determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia.A retrospective cohort study was conducted among HIV/AIDS patients taking ART from 2005 to 2010. A sample of 1540 HIV infected adult patients who started antiretroviral therapy in hospitals located in eastern Ethiopia were included in the study. The primary outcomes of interest were changes in CD4 count and weight. Descriptive statistics and multivariable regression analyses were performed to examine the outcomes among the cohort.Both the median CD4 lymphocyte counts and weight showed improvements in the follow up periods. The multivariate analysis shows that the duration of ART was an important predictor of improvements in CD4 lymphocyte count (beta 7.91; 95% CI 7.48-8.34; p 0.000 and weight (beta 0.15; 95% CI 0.13-0.18; p 0.000. Advanced WHO clinical stage, lower baseline CD4 cell count, and baseline hemoglobin levels were factors associated with decline in weight. Actively working patients had higher CD4 lymphocyte count and weight compared to those that were ambulatory (p<0.05.We detected a substantial increment in weight and CD4 lymphocyte count among the patients who were taking ART in eastern Ethiopia. Patients who are of older age, with low initial CD4 lymphocyte count, late stage of the WHO clinical stages and lower hemoglobin level may need special attention. The reasons for the improved findings on CD4 count and weight throughout the five years of follow up merit further investigation.

  20. Lycopene: An antioxidant and radioprotector against γ-radiation-induced cellular damages in cultured human lymphocytes

    International Nuclear Information System (INIS)

    Srinivasan, M.; Devipriya, N.; Kalpana, K.B.; Menon, Venugopal P.

    2009-01-01

    The present study aimed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid on γ-radiation-induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by cytokinesis blocked micronucleus assay (CBMN), dicentric aberration (DC) and translocation frequency. The γ-radiation at different doses (1, 2 and 4 Gy) resulted in a significant increase in the number of micronuclei (MN), DC, translocation frequency, TBARS and HP level, whereas the levels of GSH and antioxidant enzymes were significantly decreased when compared with normal control. The maximum damage to lymphocytes was observed at 4 Gy irradiation. Lycopene pretreatment (1, 5 and 10 μg/ml) significantly decreased the frequency of MN, DC and translocation when compared with γ-radiation control. The levels of TBARS, HP were also decreased and activities of SOD, CAT and GPx were significantly increased along with GSH levels when compared with γ-radiation control. The dose of 5 μg/ml of lycopene was found to be more effective than the other two doses. Thus, our result shows that pretreatment with lycopene offers protection to normal lymphocytes against γ-radiation-induced cellular damage.

  1. 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

  2. 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.

  3. 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...

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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 ...

  14. 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...

  15. 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 ...

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Spleen lymphocyte function modula