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Sample records for lymphocyte proliferation index

  1. Effect of praziquantel on human lymphocyte proliferation in vitro

    DEFF Research Database (Denmark)

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

    1984-01-01

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

  2. Lymphocytes in patients with psoriasis promote proliferation of keratinocytes

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

  3. Epithelial cell proliferation and glandular atrophy in lymphocytic gastritis: Effect of H pylori treatment

    Institute of Scientific and Technical Information of China (English)

    Johanna M. Makinen; Seppo Niemela; Tuomo Kerola; Juhani Lehtola; Tuomo J. Karttunen

    2003-01-01

    AIM: Lymphocytic gastritis is commonly ass ociated with Helicobacter pylori infection. The presence of glandular atrophy and foveolar hyperplasia in lymphocytic gastritis suggests abnormalities in cell proliferation and differentiation,forming a potential link with the suspected association with gastric cancer. Our aim was to compare epithelial cell proliferation and morphology in H pylori associated lymphocytic gastritis and H pylori gastritis without features of lymphocytic gastritis,and to evaluate the effect of H pylori treatment.METHODS: We studied 14 lymphocytic gastritis patients with H pylori infection. For controls, we selected 14 matched dyspeptic patients participating in another treatment trial whose H pylori infection had successfully been eradicated.Both groups were treated with a triple therapy and followed up with biopsies for 6-18 months (patients) or 3 months (controls). Blinded evaluation for histopathological features was carried out. To determine the cell proliferation index,the sections were labeled with Ki-67 antibody.RESULTS: Before treatment, lymphocytic gastritis was characterized by foveolar hyperplasia (P=0.001) and glandular atrophy in the body (P=0.008), and increased proliferation in both the body (P=0.001) and antrum (P=0.002). Proliferation correlated with foveolar hyperplasia and inflammation activity. After eradication therapy, the number of intraepithelial lymphocytes decreased in the body (P=0.004)and antrum (P=0.065), remaining higher than in controls (P<0.001). Simultaneously, the proliferation index decreased in the body from 0.38 to 0.15 (P=0.043), and in the antrum from 0.34 to 0.20 (P=0.069), the antral index still being higher in lymphocytic gastritis than in controls (P=0.010).Foveolar hyperplasia and glandular atrophy in the body improved (P=0.021), reaching the non-LG level.CONCLUSION: In lymphocytic gastritis, excessive epithelial cell proliferation is predominantly present in the body, where it associates with

  4. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  5. Effect of oral proguanil on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

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

  6. Effect of catecholamines and thermal exposure on lymphocyte proliferation, IL-1α & β in buffaloes

    Directory of Open Access Journals (Sweden)

    R.C. Upadhyay

    2010-02-01

    Full Text Available In order to study the effect of catecholamines (epinephrine/norepinephrine and thermal exposure on in vitro buffalo Lymphocyte Proliferation (LP apparently healthy 2- 2 1/2 years old Murrah buffalo heifers maintained as per the standard feeding and management practices were selected from Institute herd. Jugular blood was collected in the forenoon on the day of experiment and processed for Total Leucocyte Count (TLC and Differential Leucocyte Count (DLC. Lymphocyte proliferation assays were performed using whole blood and cells were incubated with epinephrine and norepinephrine (1, 1.5,2 ng/ml at 37oC with 5% CO2. Cells were counted after 72 hrs of incubation and Lymphocyte Proliferation Index (LPI was calculated. Thermal stress effect on the cultures was observed after exposure at 45oC for 4 hr after 72hrs of incubation. The cells were separated from media and media was used for analysis of IL-1α & 1β by ELISA kit. Lymphocyte proliferation Index decreased in responses to Epinephrine and Norepinephrine (P<0.01. Concentration of epinephrine and norepinephrine (1, 1.5,2 ng /ml had no distinguishable effect on LPI. IL-1α & IL-1β levels when compared with control in supernatant (exposed to 45°C were low (P<0.01 and P<0.05, respectively. There was a significant positive correlation between LPI and IL-1α (r=0.80; P<0.01 and between LPI and IL-1β (r=0.78; P<0.05. The study indicated that lymphocyte proliferation in vitro and IL-1α & β levels were affected by catecholamines and thermal exposure. Further the levels of catecholamines had significant (P<0.01 negative effect on LPI indicating that catecholamines levels modulate immunity through IL-1α and IL-1β in buffaloes.

  7. Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation.

    Science.gov (United States)

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

    2016-02-01

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

  8. Effects of low dose oxymatrine on mouse lymphocyte proliferation stimulated by Con A

    Institute of Scientific and Technical Information of China (English)

    LI Luo-si; WU Bin; LI Jian-guo; XIE Hong-fu; ZHANG Yang-de; CONG Ling; SHI Jun

    2005-01-01

    Objective To investigate the effects of low dose Oxymatrine (OMT) on mouse lymphocyte proliferation stimulated by Con A making use of fluorescence dyestuff CFDA-SE. Methods CFDA-SE staining and flow cytometry were used to detect the fluorescence intensity of lymphocytes after stimulated by polyclonal stimulators Con A and OMT. Then, related software was used to analyze the effects of OMT on mouse lymphocyte proliferation.Results After cultured for 48 h, CFSE fluorescence could be detected by cytometer, filial generation peaks did not appear in control group, which indicated that lymphocytes did not proliferate. Three peaks were obviously detected in Con A group which indicated that Lymphocytes divided after 48 h stimulated by Con A compared with the halving of the fluorescence intensity of control group. In groups with Con A and OMT treated, Primary generation peaks are all lower while filial generation peaks are significantly higher than groups with Con A treated only. This indicated OMT obviously promote lymphocyte proliferation. After cultured for 72 h, the fluorescence intensity changes between all groups are consistent with those of cultured for 48 h. Analyzed with CELLQuest software, it is shown that OMT could promote lymphocyte proliferation in 16, 8, 4 and 2μg/mL respectively. Conclusions 1) CFDA-SEdyeing and flow cytometer were both reliable tools to analyze lymphocyte proliferation; 2) lower dosage of OMTcould promote the proliferation of lymphocyte as a immunopotentiator.

  9. Effect of propolis on mitotic and cellular proliferation indices in human blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Montoro, A.; Almonacid, M.; Villaescusa, J. [Valencia Hospital Univ. la Fe, Servicio de Proteccion Radiologica (Spain); Barquinero, J. [Barcelona Univ. Autonom, Servicio de Dosimetria Biologica, Unidad de Antropologia, Dept. de Biologia Animal, Vegetal y Ecologia, barcelona (Spain); Barrios, L. [Barcelona Univ. Autonoma, Dept. de Biologia Celular y Fisiologia. Unidad de Biologia Celular (Spain); Verdu, G. [Valencia Univ. Politecnica, Dept. de Ingenieria Quimica y Nuclear (Spain); Perez, J. [Hospital la Fe, Seccion de Radiofisica, Servicio de Radioterapia, valencia (Spain)

    2006-07-01

    The study of the frequency of chromosomal aberrations per cell is the tool used in Biological dosimetry studies. Using dose-effect calibration curve obtained in our laboratory, we can evaluate the radioprotector effect of the EEP (ethanolic extract of propolis) in cultures in vitro. Propolis is the generic name for resinous substance collected by honeybees. The results showed a reduction in chromosomal aberrations's frequency of up to 50 %. The following study consisted of analyzing human peripheral blood lymphocytes exposed to 2 Gy {gamma} rays, in presence and absence of EEP, the change in the frequency of chromosome aberrations was analysed with biological dosimetry. The protection against the formation of dicentric and ring was dose-dependent, but there seemed to be a maximum protection, i.e. a further increase in the concentration of EEP does not show additional protection. This work studies the effect of the EEP of the cellular cycle using the mitotic and cellular proliferation index, as an alternative for the screening cytostatic activity. The results indicate that the lymphocytes which were cultures in presence of EEP exhibited a significant and dependent-concentration decrease in mitotic index and proliferation kinetics. The possible mechanisms involved in the radioprotective influence of EEP are discussed. (authors)

  10. Effect of Piper chaba Hunter, Piper sarmentosum Roxb. and Piper interruptum Opiz. on natural killer cell activity and lymphocyte proliferation.

    Science.gov (United States)

    Panthong, Sumalee; Itharat, Arunporn

    2014-08-01

    Immune system is the most important system ofhuman body. Thaifolk doctors have used some medicinal plants as an adaptogenic drug or immunomodulatory agent. Piper chaba Hunter, Piper sarmentosum Roxb. and Piper interruptum Opiz. are used by folk doctors to activate immune response in cancer patients. To investigate the effect on natural killer cell activity and on lymphocyte proliferation activity of water extract of P chaba Hunter P. sarmentosum Roxb. and P interruptum Opiz. MATERIAL ANDMETHOD: Plant materials were extracted by decoction method. All extracts were testedfor an immunomodulatory effect using PBMCs from twelve healthy donors by chromium release assay. Lymphocyte proliferation was also determined by 3H-thymidine uptake assay. The degree of activation was expressed as the stimulation index. The water extract of P chaba Hunter significantly increased lymphocyte proliferation at concentrations ofl ng/ml, 10 ng/ml, 1 μg/ml, 5 μg/ml, 10 μg/ml and 100 μg/ml. P sarmentosum Roxb., and P interruptum Opiz. extracts at those concentrations significantly stimulated lymphocyteproliferation. P sarmentosum Roxb. extractsignificantly increased natural killer (NK) cell activity at a concentration of 100 μg/ml but P chaba Hunter and P interruptum Opiz. extracts did not significantly stimulate natural killer cell activity. P chaba Hunter, P interruptum Opiz. andP sarmentosum Roxb. have an immunomodulatory effect especially for P sarmentosum Roxb. extract which can activate both lymphocyte proliferation and NK cell activity.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

    Science.gov (United States)

    McGillis, J P; Park, A; Rubin-Fletter, P; Turck, C; Dallman, M F; Payan, D G

    1989-07-01

    The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.

  13. Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients.

    Science.gov (United States)

    George, Alex; Dey, Rupraj; Bhuria, Vikas; Banerjee, Shouvik; Ethirajan, Sivakumar; Siluvaimuthu, Ashok; Saraswathy, Radha

    2014-01-01

    Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where pnuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (pproliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

  14. DMPD: Induction of proliferation and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11090938 Induction of proliferation and cytokine production in human T lymphocytes ... (.png) (.svg) (.html) (.csml) Show Induction of proliferation and cytokine production in human T lymphocyte...and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). Authors Ulmer AJ, Flad H, Rietsch

  15. Effect of thapsigargin on cytoplasmic Ca2+ and proliferation of human lymphocytes in relation to AIDS

    DEFF Research Database (Denmark)

    Scharff, O; Foder, B; Thastrup, Ole

    1988-01-01

    response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas...... of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects...

  16. Differential expression of alkaline phosphatase gene in proliferating primary lymphocytes and malignant lymphoid cell lines.

    Science.gov (United States)

    Latheef, S A A; Devanabanda, Mallaiah; Sankati, Swetha; Madduri, Ramanadham

    2016-02-01

    Alkaline Phosphatase (APase) activity has been shown to be enhanced specifically in mitogen stimulated B lymphocytes committed to proliferation, but not in T lymphocytes. APase gene expression was analyzed in proliferating murine and human primary lymphocytes and human malignant cell lines using reverse transcriptase and real time PCR. In mitogen stimulated murine splenic lymphocytes, enhancement of APase activity correlated well with an increase in APase gene expression. However, in mitogen stimulated murine T lymphocytes and human PBL despite a vigorous proliferative response, no increase in APase enzyme activity or gene expression was observed. A constitutive expression of APase activity concomitant with APase gene expression was observed inhuman myeloma cell line, U266 B1. However, neither enzyme activity nor gene expression of APase were observed in human T cell lymphoma, SUPT-1. The results suggest a differential expression of APase activity and its gene in proliferating primary lymphocytes of mice and humans. The specific expression of APase activity and its gene only in human myeloma cells, but not in proliferating primary B cells can be exploited as a sensitive disease marker.

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

    Science.gov (United States)

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

    2005-02-10

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

  18. Studying the proliferation of human peripheral blood T lymphocytes in serum-free medium.

    Science.gov (United States)

    Tabakov, V U; Litvina, M M; Schepkina, J V; Jarilin, A A; Chestkov, V V

    2009-01-01

    We compared the cultivation of human peripheral blood lymphocytes in serum-free medium Hybris-2 and RPMI 1640 medium with 10% fetal bovine serum in the presence of phytohemagglutinin and interleukin-2. The optimal concentration of phytohemagglutinin significantly differed in serum-free and serum-containing media (0.5 and 5 microg/ml, [corrected] respectively). Both mitogens were more potent in stimulating the proliferation of lymphocytes in serum-free medium than in serum-containing medium. Strong proliferation of CD3(+) and CD4(+) T lymphocytes was observed in both media. The dynamics of other markers was similar in serum-free and serum-containing media. However, significant differences were revealed between individual donors. Our results indicate that the developed serum-free medium may be used in lymphocyte cultivation for scientific, diagnostic, and therapeutic purposes.

  19. Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases

    DEFF Research Database (Denmark)

    Theander, T G; Kharazmi, A; Pedersen, B K

    1988-01-01

    This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference......, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment...... of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions....

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

    Science.gov (United States)

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

    2013-06-01

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

  2. Flow cytometric analysis of T lymphocyte proliferation in vivo by EdU incorporation.

    Science.gov (United States)

    Sun, Xiaojing; Zhang, Chunpan; Jin, Hua; Sun, Guangyong; Tian, Yue; Shi, Wen; Zhang, Dong

    2016-12-01

    Monitoring T lymphocyte proliferation, especially in vivo, is essential for the evaluation of adaptive immune reactions. Flow cytometry-based proliferation assays have advantages in measuring cell division of different T lymphocyte subsets at the same time by multicolor labelling. In this study, we aimed to establish the use of 5-Ethynyl-2'-deoxyuridine (EdU) incorporation in vivo to monitor T lymphocyte proliferation by flow cytometry with an adoptive transfer model. We found that fixation followed by permeabilization preserved T cell surface antigens and had no obvious effects on the fluorescence intensity of APC, PE, PE-Cy7, FITC and PerCP-Cy5.5 when the concentration of the permeabilization reagents was optimized. However, the click reaction resulted in a significant decrease in the fluorescence intensity of PE and PE-Cy7, and surface staining after the click reaction improved the fluorescence intensity. Thus, an extra step of blocking with PBS with 3% FBS between the click reaction and cell surface staining is needed. Furthermore, the percentage of EdU-positive cells increased in a dose-dependent manner, and the saturated dose of EdU was 20mg/kg. Intraperitoneal and intravenous injection had no differences in lymphocyte proliferation detection with EdU in vivo. In addition, T cell proliferation measured by EdU incorporation was comparable to BrdU but was lower than CFSE labelling. In conclusion, we optimized the protocols for EdU administration in vivo and staining in vitro, providing a feasible method for the measurement of T lymphocyte proliferation with EdU incorporation by flow cytometry in vivo.

  3. Lamprey buccal gland secretory protein-2 (BGSP-2 inhibits human T lymphocyte proliferation

    Directory of Open Access Journals (Sweden)

    Jing SUN, Shuiyan YU, Zhuang XUE, Cenjie LIU, Yu WU, Xin LIU, Qingwei LI

    2010-04-01

    Full Text Available Lamprey is a representative of the agnathans, the most ancient class of vertebrates. Parasitic lampreys secrete anticoagulant from their buccal glands and prevent blood coagulation of host fishes. We identified a buccal gland secretory protein-2 (BGSP-2 from a buccal gland cDNA library of Lampetra japonica. The full-length BGSP-2 gene was cloned and the recombinant BGSP-2 protein was generated. The role of BGSP-2 on lymphocyte proliferation was studied by examining its effects on human T lymphocytes. We found that lamprey BGSP-2 was able to effectively block the proliferation of T cells in vitro by inducing G1/S cell cycle arrest. Furthermore, it inhibited the proliferation of human T lymphocytes stimulated by phytohemagglutinin (PHA at a minimum concentration of 0.1μg/ml. Our data suggest that lamprey BGSP-2 is able to block the mitosis of human T lymphocytes at the G1/S point, and has the potential of anti-proliferative effect on PHA-activated T lymphocytes [Current Zoology 56 (2: 252–258, 2010].

  4. Effects of feeding lipids of different fatty acid compositions upon rat lymphocyte proliferation.

    Science.gov (United States)

    Calder, P C; Costa-Rosa, L F; Curi, R

    1995-01-01

    Weanling Wistar rats were fed for 8 weeks on a low fat (3% by weight) diet (LF) or on diets containing 15% by weight hydrogenated coconut oil (coconut oil), cocoa butter, cashew kernel oil (cashew oil), canola oil or soya bean oil (soya oil). Each of the high fat diets resulted in inhibition of spleen lymphocyte proliferation in response to concanavalin A (Con A), a T-cell mitogen. Feeding the soya oil diet caused more than 95% inhibition of proliferation, compared with feeding the LF diet. Amongst the high fat diets, feeding the cashew, canola or soya oil diets resulted in inhibition of proliferation compared with feeding the coconut oil diet while feeding the soya oil diet resulted in inhibition of proliferation compared with feeding the cocoa butter or canola oil diets. Proliferation of lymphocytes in response to Con A was also investigated using whole blood culture. Once again, feeding the soya oil diet resulted in a dramatic decrease in proliferation (80%) compared with feeding the LF diet. Feeding the soya oil diet also inhibited proliferation compared with feeding the coconut oil, cocoa butter or cashew oil diets. Feeding the canola oil diet resulted in inhibition of proliferation compared with feeding the LF or cocoa butter diets.

  5. N-acetylcysteine reverses immunotoxic effects of methyl mercury and augments murine lymphocyte proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Omara, F.; Fournier, M.; Bernier, J. [Univ. du Quebec, Montreal, Quebec (Canada); Blakley, B.

    1995-12-31

    N-Acetylcysteine (NAC) is a thiol antioxidant used clinically to treat chronic inflammatory lung disorders and acetaminophen poisoning in humans. The authors evaluated in vitro the effect of NAC on mitogen-induced blastogenesis in C57BI/6 mouse splenocytes by {sup 3}H-thymidine uptake, and its ability to protect against the immunotoxic effects of methyl mercury on lymphocyte proliferation. Lymphocyte proliferation stimulated by optimal and suboptimal concentrations of concanavalin A (Con A), lipopolysaccharide (LPS), or a combination of calcium ionophore A23187 and phorbol-12-myristate-13-acetate (PMA) were markedly enhanced by NAC. NAC itself was a weak mitogen. The kinetics of the NAC effect on splenocyte proliferation were mitogen dependent. NAC enhanced Con A-induced splenocyte proliferation in a dose-dependent and linear manner but enhanced the LPS-induced response at 50--400 {micro}g/ml of NAC followed by a decline in response to control value at higher concentrations. In splenocytes stimulated with PMA plus A23187, NAC increased proliferation at 50--200 pg/ml followed by a constant response at 200--1,000 {micro}g/ml NAC. When splenocytes were stimulated with higher concentrations of Con A (10 {micro}g/ml) or LPS (150 {micro}g/ml) which markedly suppress splenocyte proliferation, NAC significantly enhanced the Con A-induced response and reversed the inhibitory effect of high concentrations of LPS. NAC also protected lymphocytes against mitogen activation-induced cell death. Methyl mercury at 5 {times} 10{sup {minus}7}--1 {times} 10{sup {minus}6} suppressed Con A- and LPS-induced splenocyte proliferation by over 80%. However, NAC completely reversed the immunotoxic effects of methyl mercury on the mitogen-induced splenocyte proliferation even when the cells were pre-incubated with methyl mercury for 6 or 24 hr before stimulation with the mitogens.

  6. Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

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

    1986-01-01

    The in vitro effect of pyrimethamine (PYR) on human blood mononuclear cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD) was studied by 14C-thymidine incorporation, by cell counting and by total DNA estimation. PYR in concen......The in vitro effect of pyrimethamine (PYR) on human blood mononuclear cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD) was studied by 14C-thymidine incorporation, by cell counting and by total DNA estimation. PYR......-stimulated cells. The suppression of PHA-stimulated cells was reversed after one week. The increased 14C-thymidine incorporation observed in stimulated cells exposed to PYR in vitro in the early phase of proliferation did not reflect immunopotentiation but rather blocked endogenous thymidine synthesis...

  7. Effects of Euphorbia milii latex on mitogen-induced lymphocyte proliferation

    Directory of Open Access Journals (Sweden)

    I.F. Delgado

    2014-03-01

    Full Text Available The crude latex of "Crown-of-Thorns" (Euphorbia milii var hislopii, syn E.splendens is a potent plant molluscicide. For this reason, toxicological studies have been performed to evaluate the health risks posed by its use in schistosomiasis control programs. The present study is part of a more comprehensive immunotoxicological evaluation of this molluscicide. Here, we investigated the effects of E. milii latex on the proliferation of human lymphocytes in vitro. Lyophilized latex of E. milii (0, 0.5, 5, 25 and 50 µg/ml was incubated with whole blood in the presence of proliferation stimulators, i.e. lectins (phytohemagglutinin, concanavalin A and pokeweed mitogen, as well as with human monoclonal antibody against CD3 and tetanus toxoid. Cell proliferation was measured by ³H-thymidine incorporation, and the effects of latex on mitogen-induced cell proliferation were compared to the effects of 10 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA. Results showed that mitogen-induced cell proliferation was markedly enhanced by E. milii latex. This synergistic effect of latex on mitogen-induced lymphocyte proliferation may be due to the presence of TPA-like phorbol esters and/or to mitogenic plant lectins.

  8. Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes.

    Science.gov (United States)

    Doucette, Carolyn D; Rodgers, Gemma; Liwski, Robert S; Hoskin, David W

    2015-11-01

    Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice. Here, we investigated the effect of piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, piperine inhibited CD25 expression, synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of κBα, but not ZAP-70. The ability of piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders.

  9. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

    Energy Technology Data Exchange (ETDEWEB)

    Klein, T.; Pross, S.; Newton, C.; Friedman, H.

    1986-03-05

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by /sup 3/H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects.

  10. Lymphocyte Proliferation Response to S Antigen in Patients with Uveitis and Optic Neuritis

    Institute of Scientific and Technical Information of China (English)

    PeixianRen; XiuzhenYan

    1995-01-01

    Purpose:To evaluate the autoimmunity which may play a major role in the etiolo-gy of certain forms of uveitis and optic neuritis.Methods:lymphocyte proliferation response to retinal soluble antigen in vitro by gy of certain forms of uveitis and optic neuritis.Methods:Lymphocyte proliferation response toretinal soluble antigen in vitro by incoperation3H-thymidine withDNA was tested in 115patients with anterior u-veitis,posterior/pan-uveitis,optic neuritis,and 50volunteers with unrelated diseases such as congenital ptosis,strabismus,or completely healthy persons as control.Results:The positive rate of lymphocyte stimulation was34%(18/53)in anteri-or uveitis,41.5%(17/41)in posterior/pan-uveitis,and57.1%(12/21)in optic euritis,The results in the experimental groups were significantly different from those of the control group(x2=14.76,P<0.05,x2=19.14P<0.005,x2=26.38,P<0.005,respectively).Conclusion:The autoimmunity plays a role in the patogenesis in certain forms of uveitis and optic neuritis,Such immune responses may be secondary to the expo-sition or release of retinal antigens by various causes,leading to activation or augmentation of meager or low-affinity S antigen specific lymphocytes which may preexist in the circulation and starting the pathogenic autoimmune process.Eye Science 1995;11:120-123.

  11. Myxoma virus suppresses proliferation of activated T lymphocytes yet permits oncolytic virus transfer to cancer cells.

    Science.gov (United States)

    Villa, Nancy Y; Wasserfall, Clive H; Meacham, Amy M; Wise, Elizabeth; Chan, Winnie; Wingard, John R; McFadden, Grant; Cogle, Christopher R

    2015-06-11

    Allogeneic hematopoietic cell transplant (allo-HCT) can be curative for certain hematologic malignancies, but the risk of graft-versus-host disease (GVHD) is a major limitation for wider application. Ideally, strategies to improve allo-HCT would involve suppression of T lymphocytes that drive GVHD while sparing those that mediate graft-versus-malignancy (GVM). Recently, using a xenograft model, we serendipitously discovered that myxoma virus (MYXV) prevented GVHD while permitting GVM. In this study, we show that MYXV binds to resting, primary human T lymphocytes but will only proceed into active virus infection after the T cells receive activation signals. MYXV-infected T lymphocytes exhibited impaired proliferation after activation with reduced expression of interferon-γ, interleukin-2 (IL-2), and soluble IL-2Rα, but did not affect expression of IL-4 and IL-10. MYXV suppressed T-cell proliferation in 2 patterns (full vs partial) depending on the donor. In terms of GVM, we show that MYXV-infected activated human T lymphocytes effectively deliver live oncolytic virus to human multiple myeloma cells, thus augmenting GVM by transfer of active oncolytic virus to residual cancer cells. Given this dual capacity of reducing GVHD plus increasing the antineoplastic effectiveness of GVM, ex vivo virotherapy with MYXV may be a promising clinical adjunct to allo-HCT regimens.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. The immunosuppressive effect of gossypol in mice is mediated by inhibition of lymphocyte proliferation and by induction of cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Wen-bin XU; Li-hui XU; Hong-song LU; Dong-yun OUYANG; Huan-jing SHI; Jing-fang DI; Xian-hui HE

    2009-01-01

    Aim: To investigate the immunosuppressive effect of gossypol in mice both in vitro and in vivo.Methods: The in vitro effect of gossypol on the proliferation of lymphocytes isolated from lymph nodes of BALB/c mice was determined by CFSE staining and by an MTS assay. Lymphocyte activation and lymphoblastic transformation were evaluated with immunostaining. Cell apoptosis was detected by Annexin-V and Hoechst 33342 staining. The in vivo immunosuppressive effect of gossypol on the DTH reaction was evaluated using a mouse DTH model induced by 2,4-dinitro-1-fluorobenzene (DNFB). The thickness of the ears was measured, and the histological changes of the mouse auricles were observed after hematoxylin-eosin staining. The proliferation capacity of lymphocytes from DTH mice was also assayed.Results: In vitro, gossypol could significantly inhibit the proliferation of mouse lymphocytes stimulated with phorbol ester plus ionomycin in a dose-dependent manner. Although the expression of the early activation antigen CD69 was not affected, the lymphoblastic transformation of both T and B lymphocyte subsets was significantly suppressed by gossypol.Moreover, gossypol could induce apoptosis of lymphocytes, and the effect was time- and dose-dependent. In vivo, the DTH reaction in mice was markedly alleviated by gossypol injected intraperitoneally. Lymphocytes from drug-treated DTH mice had a reduced proliferation capacity as compared with lymphocytes from untreated DTH mice. Gossypol treatment also markedly reduced the number of infiltrated lymphocytes in the auricles of DTH mice. Conclusion: Gossypol exhibited immunosuppressive effects in mice, probably by inhibition of lymphocyte proliferation and by induction of cell apoptosis.

  14. IMMUNOMODULATION OF SYNTHESIZED POLYMERS CONTAINING PHOSPHORUS IN THE BACKBONE —EFFECT ON THE PROLIFERATION OF LYMPHOCYTES

    Institute of Scientific and Technical Information of China (English)

    ZhuoRenxi; WangJun; 等

    1997-01-01

    The immunomodulation of several Charged synthetic polymers containing phosphorus in the backbone was studied in vitro through examining their inhibition or promotion effect on the proliferatioin of both T and B lymphocytes,It is found that polymers based on long chain alkyl ester of tyrosine exhibit immunomodulative activity.Negatively charged polymers show stimulative activity on LPS-induced B lymphocytes proliferation.Positively charged polymers exhibit inhibitory activity on both Con A-induced T lymphocytes and LPS-induced B lymplhyocytes proliferation.

  15. Mycoplasma contamination revisited: mesenchymal stromal cells harboring Mycoplasma hyorhinis potently inhibit lymphocyte proliferation in vitro.

    Directory of Open Access Journals (Sweden)

    Severin Zinöcker

    Full Text Available BACKGROUND: Mesenchymal stromal cells (MSC have important immunomodulatory effects that can be exploited in the clinical setting, e.g. in patients suffering from graft-versus-host disease after allogeneic stem cell transplantation. In an experimental animal model, cultures of rat T lymphocytes were stimulated in vitro either with the mitogen Concanavalin A or with irradiated allogeneic cells in mixed lymphocyte reactions, the latter to simulate allo-immunogenic activation of transplanted T cells in vivo. This study investigated the inhibitory effects of rat bone marrow-derived MSC subsequently found to be infected with a common mycoplasma species (Mycoplasma hyorhinis on T cell activation in vitro and experimental graft-versus-host disease in vivo. PRINCIPAL FINDINGS: We found that M. hyorhinis infection increased the anti-proliferative effect of MSC dramatically, as measured by both radiometric and fluorimetric methods. Inhibition could not be explained solely by the well-known ability of mycoplasmas to degrade tritiated thymidine, but likely was the result of rapid dissemination of M. hyorhinis in the lymphocyte culture. CONCLUSIONS: This study demonstrates the potent inhibitory effect exerted by M. hyorhinis in standard lymphocyte proliferation assays in vitro. MSC are efficient vectors of mycoplasma infection, emphasizing the importance of monitoring cell cultures for contamination.

  16. Correlation of thyroid cancer Doppler hemodynamic indexes with tumor proliferation and angiogenesis indexes

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Jin Zhang; Jian-Jun Zhang; Hui Sun

    2016-01-01

    Objective:To explore the correlation of thyroid cancer Doppler hemodynamic indexes with tumor proliferation and angiogenesis indexes.Methods:A total of 108 cases of thyroid cancer were diagnosed by B-ultrasound and pathology and then included in the observation group of the research, 107 cases of non-cancer patients who received excision of thyroid adenoma in our hospital during the same period were selected as healthy control group, thyroid hemodynamic indexes, tumor proliferation-related indexes and serum angiogenesis-related indexes of two groups were detected, and the correlation of thyroid cancer hemodynamic indexes with tumor proliferation and angiogenesis indexes was further analyzed.Results:S and D values of observation group were higher than those of control group (P0.05); p53, PCNA and Ki-67 expression levels in thyroid tumor of observation group were higher than those of control group while TIPE2 protein expression level was lower than that of control group (P<0.05); serum VEGF, Ang-2, HIF-1α, IGF-Ⅱ and endostatin values of observation group were higher than those of control group while MBP value was lower than that of control group (P<0.05); thyroid artery peak systolic velocity (S) and end diastolic velocity (D) were directly proportional to p53, PCNA, Ki-67, VEGF, Ang-2, HIF-1α, IGF-Ⅱ and endostatin values, and inversely proportional to TIPE2 and MBP values (P<0.05).Conclusions:Artery blood flow velocity in patients with thyroid cancer is directly correlated with tumor proliferation and angiogenesis, and can be used as the reliable index to judge tumor condition and curative effect.

  17. An Experimental Study on the Role of Nuclear Factor-κB in the Signal Conduction of Protein Kinase C Regulating the Proliferation and Apoptosis of T Lymphocytes in Asthma

    Institute of Scientific and Technical Information of China (English)

    熊维宁; 徐永健; 张珍祥; 王孝养

    2004-01-01

    To explore the role of nuclear factor-κB(NF-κB) in the signal pathway of protein kinase C (PKC) regulating the proliferation and apoptosis of T lymphocytes in asthma. T lymphocytes were isolated from the asthmatic model of guinea pigs and the asthmatic patients. Either the T cells stimulated with PMA alone or those stimulated with PMA together with pyrrolidine dithiocarbamate (PDTC) were incubated for 1 and 24 h. The proliferation of and the presence of NF-κB in the cells incubated for 1 h were observed by MTT and immunohistochemical staining, respectivelyAnd the cells incubated for 24 h were observed for the apoptosis by TUNEL. All the assays were paralleled with controls, and all the data were analyzedstatistically with the software SAS. The percentage of cells of nuclear positive staining of NF-scB and the proliferation of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly higher than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively ( P < 0.01 ) and those of T lymphocytes from normal control guinea pigs and normal control persons stimulated with PMA respectively ( P < 0.01 ), and were significantly reduced by PDTC (P < 0.01 ). The apoptosis index of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly lower than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively ( P < 0.01 ) and those of T lymphocytes from normal control guine apigs and normal control persons stimulated with PMA respectively ( P < 0.01 ), and were significantly induced by PDTC ( P< 0.01 ). There were good positive correlation between the percentage of cells of nuclear staining of NF-κB ofT lymphocytes and the proliferation of T lymphocytes ( r = 0.51-0.72, P < 0.001 ), and also good negative correlation between the percentage of cells of nuclear staining of NF-scB and the

  18. Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages.

    Science.gov (United States)

    Routray, Indusmita; Ali, Shakir

    2016-01-01

    Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.

  19. Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages.

    Directory of Open Access Journals (Sweden)

    Indusmita Routray

    Full Text Available Chemical mediators of inflammation (CMI are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO, were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.

  20. Ki-67 proliferation index and clinicopathological patterns in colorectal carcinomas

    Directory of Open Access Journals (Sweden)

    Bhagya Lakshmi A

    2015-04-01

    Full Text Available Background : Tumour, Node, Metastasis (TNM staging system provides useful prognostic information in patients with colorectal carcinoma (CRC. An improved prognostication and patient survival may be achieved by employing immunohistochemistry studies with proliferation markers like Ki-67. Materials and methods: We prospectively studied 51 patients with CRC and evaluated the clinicopathological patterns of CRC and the relationship of with the clinicopathological variables Results: Their mean age was 48 (range 17-75 years; majority (64.7% were males. Rectum was the most common subsite affected (45.1%. Histopathologically most of the tumours (86.3% were usual type adenocarcinomas and were of grade 1 morphology (51%. The Ki-67 proliferation index (PI ranged from 8.4% to 84.4%. The mean PI was greater in patients aged less than or equal to 50 years than in those aged above 50 years, in males than females, in rectal cancers than colonic cancers. It was greater in mucinous carcinomas than usual type adenocarcinomas, in grade 3 tumours than lower grade tumours (grades 1 and 2 and in T4 than T3 and T2 tumours. There was a significant positive correlation between the PI values and grade of the tumour. Conclusion: We concluded that Ki-67 proliferation marker may be useful as an additional tool to assess the tumour aggressiveness with respect to certain clinicopathological parameters in colorectal carcinomas.

  1. Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index

    Institute of Scientific and Technical Information of China (English)

    Li ZENG; Xiang-Tian KONG; Jin-Wei SU; Tong-Li XIA; Yan-Qun NA; Ying-Lu GUO

    2001-01-01

    To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. Methods: Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. Results: The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis ( 14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar Pis (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. Conclusion: PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.

  2. PROLIFERATION RESPONSES IN PREIMMUNIZED MICE LYMPHOCYTES BY BORDETELLA PERTUSSIS CELL WALL COMPONENTS

    Directory of Open Access Journals (Sweden)

    Ashraf Mohabbati Mobarez

    2003-03-01

    Full Text Available Bordetella pertussis infects the respiratory tract of the human host and causes whooping cough in children. The nature of immunity against Bordetella pertussis infection and disease is poorly understood. The aim of this study was to investigate cell mediated immunity in mice immunized with outer membrane component of cell wall, of B. Pertussis.A group of mice were immunized with outer membrane complex (OMC and killed whole cell (WCV of B. pertussis, with an interval of 2 weeks. During a period of 7 weeks following the immunization, lymphocytes were isolated from lymph nodes of immunized mice. The in vitro proliferative response of isolated lymphocyte to stimulation with 20 ^g of 30 and 69 kDa outer membrane protein (OMP were measured as parameters for cell mediated immunity (CMI. The data were expressed as mean count per minute (CPMxlO3 after subtraction of the CPM of unstimulated control cultures. Lymphoblastogenic response was observed in immunized mice with WCV and OMC. At 30 days of post immunization a significant increase in response to 30 and 69 kDa OMP was observed, a small decrease in the response was evident against P30 and P69 at 60 and 120 days of post immunization, but the response was still higher than what was observed in control mice.Current findings indicate strongly the potential of outer membrane protein component of B. pertussis in proliferating lymphocytes in the mice.

  3. Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production.

    Science.gov (United States)

    Dobis, Dave R; Sawyer, Richard T; Gillespie, May M; Newman, Lee S; Maier, Lisa A; Day, Brian J

    2010-10-01

    Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD, and may serve as novel therapy for human granulomatous lung diseases.

  4. 50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

    Science.gov (United States)

    Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

    2004-12-01

    In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

  5. Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Mitxelena, Jone; Sánchez-Quiles, Virginia;

    2016-01-01

    Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms...... and inducing the expression of cell cycle regulating genes in response to IL-2. Thus, the metabolic enzyme ACLY emerges as a bridge between cytokine signaling and proliferation of T lymphocytes, and may be an attractive candidate target for the development of more efficient anti-cancer immunotherapies....

  6. Ambiguous nucleus regulates the proliferation and percentage of T lymphocytes in peripheral blood

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Wei Chen; Yingwu Mei; Bin Guo; Zhanqing Yang; Shoupeng Fu; Zhanpeng Yue; Juxiong Liu

    2011-01-01

    The aim of this study was to examine the immunomodulatory role of the unilateral ambiguous nucleus (Amb). We performed electrical stimulation of the unilateral Amb, electrical stimulation of the left parietal cortex and the lateral hypothalamus following unilateral Amb lesion, as well as microinjection of acetylcholine chloride and hemicholine-3 into the unilateral Amb, and electrical stimulation of the unilateral Amb after injection of atropine, mecamylamine, propranolol, and phentolamine. Results showed that the number and proliferation of peripheral blood T lymphocytes were increased after electrical stimulation of the unilateral Amb. The cholinergic neurons in the Amb released choline substances to alter cellular immunity, thus confirming that the Amb mediates the neuro-immunomodulatory process.

  7. Effect of Protein Kinase C on Proliferation and Apoptosis of T Lymphocytes in Idiopathic Thrombocytopenic Purpura Children

    Institute of Scientific and Technical Information of China (English)

    Changlin Wu; Fang Liu; Xuemin Zhou; Zhengwei Cheng; Xiaomeng Yang; Hong Xiao; Qun Chen; Kangrong Cai

    2005-01-01

    It is well-documented that T lymphocyte proliferation and apoptosis are abnormal in idiopathic thrombocytopenic purpura (ITP) children. However, the underlying regulation mechanisms especially in terms of signal transduction remain unknown. In this paper, we reported the changes of protein kinase C (PKC) activity in peripheral blood T lymphocytes and the effect of PKC on T lymphocyte proliferation and apoptosis. We demonstrated that in ITP children, the activator (PMA) and inhibitor (H-7) of PKC affected on T lymphocyte proliferation and apoptosis dramatically, but they altered little in healthy children. PKC activity was significantly enhanced in ITP children together with an increased expression of FasL on CD3+ T, CD4+ T and CD8+T cells, resulting in a positive correlation between PKC activity and the expression of FasL on T cells. While the PKC activity and the platelet count were negatively correlated. Taken together, our findings suggest that the PKC activation may enhance T lymphocytes activity, suppress T cell apoptosis and be involve in thrombocytes damage as a mechanism related to immune pathogenesis of ITP.

  8. Setae from larvae of the northern processionary moth (Thaumetopoea pinivora, TP) stimulate proliferation of human blood lymphocytes in vitro.

    Science.gov (United States)

    Holm, Göran; Andersson, Margareta; Ekberg, Monica; Fagrell, Bengt; Sjöberg, Jan; Bottai, Matteo; Björkholm, Magnus

    2014-01-01

    Larvae of the Northern pine processionary moth (Thaumetopoea pinivora, TP) carry microscopic needles (setae), which by penetrating skin and mucous membranes, may cause inflammatory/immune derived symptoms in man. In the present study the stimulatory effects of setae on human blood lymphocytes in vitro was investigated. Blood mononuclear cells were separated from venous blood or buffy coat of ten healthy individuals, six previously exposed to setae and four with no known exposure. Lymphoproliferation was measured as uptake of 3H-thymidine. Setae were prepared from TP larvae. Setae and saline setae extracts stimulated proliferation of T-lymphocytes in the presence of monocytic cells. Stimulation was pronounced in cells from persons who had been exposed to setae, and weak in cells from non-exposed donors. Chitin also induced lymphocyte proliferation in most donors, but to a lesser extent and independently of donor's previous exposure to setae. In conclusion, setae contain molecules that in the presence of monocytes activate human T-lymphocytes to proliferation. The antigenic nature of stimulatory molecules was supported by the significantly stronger lymphocyte response in persons previously exposed to setae than in non-exposed donors. The nature of such molecules remains to be defined.

  9. Setae from larvae of the northern processionary moth (Thaumetopoea pinivora, TP stimulate proliferation of human blood lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Göran Holm

    Full Text Available Larvae of the Northern pine processionary moth (Thaumetopoea pinivora, TP carry microscopic needles (setae, which by penetrating skin and mucous membranes, may cause inflammatory/immune derived symptoms in man. In the present study the stimulatory effects of setae on human blood lymphocytes in vitro was investigated. Blood mononuclear cells were separated from venous blood or buffy coat of ten healthy individuals, six previously exposed to setae and four with no known exposure. Lymphoproliferation was measured as uptake of 3H-thymidine. Setae were prepared from TP larvae. Setae and saline setae extracts stimulated proliferation of T-lymphocytes in the presence of monocytic cells. Stimulation was pronounced in cells from persons who had been exposed to setae, and weak in cells from non-exposed donors. Chitin also induced lymphocyte proliferation in most donors, but to a lesser extent and independently of donor's previous exposure to setae. In conclusion, setae contain molecules that in the presence of monocytes activate human T-lymphocytes to proliferation. The antigenic nature of stimulatory molecules was supported by the significantly stronger lymphocyte response in persons previously exposed to setae than in non-exposed donors. The nature of such molecules remains to be defined.

  10. Regulatory substances produced by lymphocytes. V. Production of inhibitor of DNA synthesis (IDS) by proliferating T lymphocytes.

    Science.gov (United States)

    Namba, Y; Jegasothy, B V; Waksman, B H

    1977-04-01

    The conditions neccessary for production of inhibitor of DNA synthesis (IDS) by rat lymphocytes were investigated. In concanavalin A (Con A)-stimulated lymph node cell (LNC) cultures, IDS production was not detected in the culture supernatant during the first 24 hr, and it increased gradually after that to reach a maximum at 3 to 4 days. When the cells were pretreated with mitomycin C, IDS was not produced, suggesting that DNA synthesis of LNC or a LNC subpopulation is necessary for IDS production. In contrast, Con A-stimulated spleen cells priduced a high level of IDS within 24 hr, and its production fell off sharply thereafter. Con A-stimulated rat thymocytes also produced IDS reaching a maximum at 2 to 3 dyas. However, thymus cells from rats treated with hydrocortisone 48 hr previously did not produce IDS. This finding implies that cortisol-sensitive (cortical) thymocytes are capable of producing IDS and cortisol-resistant (medullary) thymocytes are not. IDS production by lymphoblasts was proportional to cell number and unaffected eith by cell density (1 to 10 x 106/ml) or by the concomitant presence of normal cells from spleen, lymph node, or thymus. Thus Con A-stimulated cells, after becoming blasts, appear to produce IDS automatically wihtout affecting or being affected by other cells. Both spleen and thymus cells from rats injected with a large dose of antigen (ovalbumin, 100 mg, i.p.) 24 hr in advance produced substantial amounts of IDS in culture within 24 hr in the absence of mitogen or additional antigen, but not the cells from rats injected with an immunizing dose (1 mg) of the same antigen. The cells producing IDS in the spleen were shown to be adherent to glass wool, and those in the thymus were partially so. IDS production by antigen-stimulated spleen cells was abrogated by injecting rats with bromodexyuridine (BUdR) at 0 and 12 hr after the ovalbumin. These findings suggest that a subpopulation ofadherent spleen cells (possibly resembling cortical

  11. Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Mitxelena, Jone; Sánchez-Quiles, Virginia

    2016-01-01

    Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms that are no...

  12. Antigen-specific activation and proliferation of CD4+ and CD8+ T lymphocytes from brucellosis patients.

    Science.gov (United States)

    Moreno-Lafont, Martha Cecilia; López-Santiago, Rubén; Zumarán-Cuéllar, Elena; Paredes-Cervantes, Vladimir; López-Merino, Ahidé; Estrada-Aguilera, Ariel; Santos-Argumedo, Leopoldo

    2002-01-01

    Salt-extractable antigen from Brucella melitensis 16M (RCM-BM) was used to evaluate the immune response from acute and chronic patients suffering from Brucella infections (in Mexico); their responses were compared with those of healthy controls. As a readout we used upregulation of CD69 (a well-established early activation marker for lymphocytes), lymphocyte proliferation by 3[H]thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation measured by liquid scintillation or flow cytometry, respectively, and production of gamma interferon (IFN gamma). We compared the antigen-specific response with the response induced by phytohaemagglutinin (PHA) as a positive control. There was no difference between acute patients and the healthy controls in the percentages of CD3+, CD4+ or CD8+ lymphocytes. However, we found that chronic patients had a significant (P brucellosis patients and in CD8+ T lymphocytes in chronic patients, indicating that both populations became activated by this antigen preparation. Moreover, lymphocyte proliferation from both acute and chronic patients in response to RCM-BM was highly significant (P < 0.001) when compared with healthy controls. However, there were no apparent differences between acute and chronic patients. Although the incorporation of BrdU showed similar results it provided additional information, since we demonstrated that both CD4+ and CD8+ T lymphocytes from acute and chronic patients proliferated equally well in response to RCM-BM. Similar results were observed with intracellular IFN gamma determination. As a whole, our data suggest an important role for both CD4+ and CD8+ T lymphocytes in Brucella infection in humans. As has been reported in mice, it is feasible that activated CD8+ T cells participate in protection against Brucella in humans through cytotoxicity or/and by the production of factors such as interferon and granulysin. The role of these cells should be carefully analysed to understand better their participation in human

  13. Effect of cholinomimetics and adrenomimetics on proliferation of mouse B lymphocytes during primary immune response to protein antigen

    Energy Technology Data Exchange (ETDEWEB)

    Ado, A.D.; Dontsov, V.I.; Gol' dshtein, M.M.

    1985-12-01

    The aim of this investigation was to study the effect of neurotransmitters on proliferation of B lymphocytes induced by specific antigen. Experiments were carried out on female mice. To estimate proliferative activity, lymphocytes enriched with B cells were incubated in medium 199 for 2 h at 37 degrees C in a dose of 2.10/sup 6/-5.10/sup 6/ cells with 2 microCi of /sup 3/H-(methyl)-thymidine. The effect of acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of antigen during culture is shown. Discordance of effects of adrenalin and acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of ovalbumin is also shown.

  14. Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress

    Science.gov (United States)

    Miller, E. S.; Klinger, J. C.; Akin, C.; Koebel, D. A.; Sonnenfeld, G.

    1994-01-01

    Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS).

  15. Effect of melatonin on monochromatic light-induced T-lymphocyte proliferation in the thymus of chickens.

    Science.gov (United States)

    Chen, Fuju; Reheman, Aikebaier; Cao, Jing; Wang, Zixu; Dong, Yulan; Zhang, Yuxian; Chen, Yaoxing

    2016-08-01

    A total of 360 post-hatching day 0 (P0) Arbor Acre male broilers, including intact, sham operation and pinealectomy groups, were exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) from a light-emitting diode (LED) system until for P14. We studied the effects of melatonin and its receptors on monochromatic light-induced T-lymphocyte proliferation in the thymus of broilers. The density of proliferating cell nuclear antigen (PCNA) cells and the proliferation of T-lymphocytes in response to Concanavalin A (ConA) in GL significantly increased both in vivo and in vitro (from 9.57% to 32.03% and from 34.30% to 50.53%, respectively) compared with other lights (plights (p<0.005). However, exogenous melatonin (10(-9)M) significantly increased the proliferative activity of T-lymphocyte by 9.64% (p=0.002). In addition, GL significantly increased mRNA expression levels of Mel1a, Mel1b and Mel1c receptors from 21.09% to 32.57%, and protein expression levels from 24.43% to 42.92% compared with RL (p<0.05). However, these effects were blocked after pinealectomy. Furthermore, 4P-PDOT (a selective Mel1b antagonist) and prazosin (a selective Mel1c antagonist) attenuated GL-induced T-lymphocyte proliferation in response to ConA (p=0.000). Luzindole (a nonselective Mel1a/Mel1b antagonist), however, did not induce these effects (p=0.334). These results suggest that melatonin may mediate GL-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors but not via the Mel1a receptor.

  16. Recombinant human erythropoietin treatment of chronic renal failure patients normalizes altered phenotype and proliferation of CD4-positive T lymphocytes.

    Science.gov (United States)

    Lisowska, Katarzyna A; Debska-Slizien, Alicja; Radzka, Monika; Witkowski, Jacek M; Rutkowski, Boleslaw; Bryl, Ewa

    2010-03-01

    Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4(+) T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4(+) lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4(+) T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4(+)CD95(+), CD4(+)HLA-DR(+) cells, and lower percentages of CD4(+)CD69(+) and CD4(+)CD28(+) cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4(+)CD28(+) and CD4(+)HLA-DR(+) subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPObeta. CD4(+) lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4(+)CD28(+) T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0-->G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4(+) T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.

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

    Science.gov (United States)

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

    1993-06-01

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

  18. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    Chang Dong LI; Wei Yuan ZHANG; He Lian LI; Xiao Xia JIANG; Yi ZHANG; Pei Hsien TANG; Ning MAO

    2005-01-01

    Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium.The homogenous layer of adherent cells exhibited a typical fibroblastlike morphology,a large expansive potential,and cell cycle characteristics including a subset of quiescent cells.In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic,osteogenic and chondrogenic lineages.Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells,which uniformly expressed CD29,CD44,CD73,CD 105,CD166,laminin,fibronectin and vimentin while being negative for expression of CD31,CD34,CD45 and α-smooth muscle actin.Most importantly,immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-Ⅰ),but they did not express MHC-Ⅱ molecules.Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli.This strongly implies that they may have potential application in allograft transplantation.Since placenta and UCB are homogeneous,the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.

  19. Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

    Directory of Open Access Journals (Sweden)

    Bakari Muhammad

    2009-02-01

    Full Text Available Abstract Background Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA in HIV-infected subjects with latent or active TB. Methods HIV-infected subjects with bacille Calmette Guérin (BCG scars and CD4 counts ≥ 200 cells/mm3 entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST, LPA and five day assays of interferon gamma (IFN-γ release. Assay antigens were early secreted antigenic target 6 (ESAT-6, antigen 85 (Ag85, and Mycobacterium tuberculosis whole cell lysate (WCL. Subjects were screened for active TB at enrollment by history, exam, sputum smear and culture. We compared antimycobacterial immune responses between subjects with and without latent or active TB at enrollment. Results Among 1885 subjects screened, 635 had latent TB and 13 had active TB. Subjects with latent TB were more likely than subjects without TB to have LPA responses to ESAT-6 (13.2% vs. 5.5%, P Conclusion Lymphoproliferative responses to mycobacteria are detectable during HIV-associated active TB, and are less sensitive but more specific than TST. Trial registration ClinicalTrials.gov Identifier NCT00052195.

  20. The influence of galvanic currents and voltage on the proliferation activity of lymphocytes and expression of cell surface molecules.

    Science.gov (United States)

    Podzimek, S; Hána, K; Miksovský, M; Pousek, L; Matucha, P; Meloun, M; Procházková, J

    2008-01-01

    Release of metal ions from dental metal fillings supported by galvanism can cause local or general pathological problems in sensitive and genetically susceptible individuals. We aimed to investigate in vitro lymphocyte responses and expression of surface molecules influenced by galvanic currents and voltage. Human peripheral blood lymphocytes were influenced by galvanic currents and voltages and lymphocyte proliferation was measured. Control samples were not exposed to the influence of galvanism. We also studied the expression of surface molecules by the FACS analysis. A 15-h and shorter influence of almost all tested currents and voltages caused a significant decrease in lymphocyte proliferation and the 15-h influence of 20 microA currents significantly increased expression of surface molecules CD 19, 11a/18, 19/69 and 19/95. An influence of 10 and 3 microA currents led to a significant decrease in the expression of surface molecules CD 3, 11a/18, 3/69 and 3/95 and to a significant increase in CD 19 expression. An 80 mV voltage influence led to a significant decrease in the expression of surface molecules CD 3, 11a/18, 3/69, 3/95, 19/69 and 19/95, and 200 and 300 mV voltages significantly decreased the expression of surface molecules CD 3, 19, 11a/18, 3/95 and 19/95 and significantly increased CD 19/69 expression. A long-lasting influence of galvanism can, in sensitive and genetically susceptible individuals, influence lymphocyte proliferation and surface molecule expression. The threshold for pathological values of 5 microA for galvanic currents and 100 mV for galvanic voltage was confirmed.

  1. Dietary palmitic acid influences LDL-mediated lymphocyte proliferation differently to other mono- and polyunsaturated fatty acids in rats.

    Science.gov (United States)

    Tinahones, F J; Gómez-Zumaquero, J M; Monzón, A; Rojo-Martínez, G; Pareja, A; Morcillo, S; Cardona, F; Olveira, G; Soriguer, F

    2004-10-01

    Recent studies suggest that the biological effects of saturated fatty acids depend on the length of their chain. We compared the effect of diets containing different fatty acids on plasma lipids and lymphocyte proliferation in the presence of lovastatin and with increasing amounts of LDL. Lymphocytes from rats fed with a diet rich in palmitic acid had a greater lymphocyte proliferation capacity than those from rats fed with diets rich in oleic acid, linoleic acid, or fish oil. This effect was maintained when small amounts of polyunsaturatwed fatty acids (PUFA; sunflower oil) were added to the palmitic acid diet. LDL receptor activity, measured by the capacity of lovastatin to revert the inhibition of lymphocyte proliferation with increasing amounts of LDL in the medium, was greater in the rats fed with palmitic acid, and was similar to the other groups when small amounts of PUFA were added. All the groups had similar levels of plasma cholesterol, but the LDL levels were significantly lower in the group fed with palmitic acid plus PUFA. The highest HDL-cholesterol (HDLc) levels were found in the palmitic acid group and the lowest LDL-cholesterol (LDLc)/HDLc ratio in the palmitic acid plus PUFA group. These results suggest that diets rich in palmitic acid do not raise total cholesterol, but reduce LDLc or keep it normal, and raise HDLc levels. This effect may be partly due to an increase in LDL receptor activity. The inclusion of small amounts of PUFA in the diet rich in palmitic acid substantially modified the LDL receptor response in the lymphocytes, suggesting that the proportion of different families of dietary fatty acids may be more important than the individual amount of each in absolute terms to explain their effects on plasma lipids and lipoproteins.

  2. Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

    Science.gov (United States)

    Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

    2015-12-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (pe-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers.

  3. Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes.

    Science.gov (United States)

    Osinalde, Nerea; Mitxelena, Jone; Sánchez-Quiles, Virginia; Akimov, Vyacheslav; Aloria, Kerman; Arizmendi, Jesus M; Zubiaga, Ana M; Blagoev, Blagoy; Kratchmarova, Irina

    2016-06-01

    Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms that are not clearly understood. To study the role of IL-2 in the regulation of nuclear protein function we have performed an unbiased mass spectrometry-based study of the nuclear phosphoproteome of resting and IL-2-treated CD4(+) T lymphocytes. We detected 8521distinct phosphosites including many that are not yet reported in curated phosphorylation databases. Although most phosphorylation sites remained unaffected upon IL-2 treatment, 391 sites corresponding to 288 gene products showed robust IL-2-dependent regulation. Importantly, we show that ATP-citrate lyase (ACLY) is a key phosphoprotein effector of IL-2-mediated T-cell responses. ACLY becomes phosphorylated on serine 455 in T lymphocytes upon IL-2-driven activation of AKT, and depletion or inactivation of ACLY compromises IL-2-promoted T-cell growth. Mechanistically, we demonstrate that ACLY is required for enhancing histone acetylation levels and inducing the expression of cell cycle regulating genes in response to IL-2. Thus, the metabolic enzyme ACLY emerges as a bridge between cytokine signaling and proliferation of T lymphocytes, and may be an attractive candidate target for the development of more efficient anti-cancer immunotherapies.

  4. Multicolor flow cytometry analysis of the proliferations of T-lymphocyte subsets in vitro by EdU incorporation.

    Science.gov (United States)

    Sun, Yanli; Sun, Yu; Lin, Guigao; Zhang, Rui; Zhang, Kuo; Xie, Jiehong; Wang, Lunan; Li, Jinming

    2012-10-01

    EdU (5-ethynyl-2'-deoxyuridine) incorporation has proved advantageous in the studies of cell kinetics, DNA synthesis, and cellular proliferation in vitro and in vivo compared to [(3) H]thymidine incorporation and BrdU (5-bromo-2'-deoxyuridine) incorporation. Here, we describe a method that combines EdU incorporation and immunostaining with flow cytometric analysis to detect the proliferations of T lymphocyte subsets in vitro and optimized the assay's conditions. We found that the number of EdU(+) cells were associated with EdU concentration, incubation time, and the volume of Click reaction solution, the best EdU concentration 10-50 μM, the optimal incubation time 8-12 h and the proper volume of Click volume 100 μl for labeling 1 × 10(6) lymphocytes. Fixation was better to be performed before permeabilization, not together with. Furthermore, the permeabilization detergent reagent, PBS with 0.05% saponin was better than Tris buffer saline (TBS) with 0.1% Triton X-100. In addition, sufficient wash with PBS with 0.05% saponin has no influence on the staining of EdU(+) cells. Also, the lymphocytes incorporating EdU could be stored at 4°C, -80°C, and in liquid nitrogen up to 21 days. The present study will aid in optimization of flow cytometry assay to detect the proliferations of T cell subsets by EdU incorporation and the labeling of cell surface antigens.

  5. A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Aysun Adan Gökbulut

    2015-06-01

    Full Text Available INTRODUCTION: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey, on 232B4 chronic lymphocytic leukemia (CLL cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. METHODS: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. RESULTS: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. DISCUSSION AND CONCLUSION: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

  6. Cytotoxicity and Inhibition of Lymphocyte Proliferation of Fasciculatin, a Linear Furanosesterterpene Isolated from Ircinia variabilis Collected from the Atlantic Coast of Morocco

    OpenAIRE

    Werner Herz; Maria São José Nascimento; Nair Nazareth; Anake Kijjoa; Pinho, Paulo M.; Aziz Fassouane; Saida Rifai

    2005-01-01

    Abstract: Fasciculatin, a furanosesterterpene isolated from the marine sponge Ircinia variabilis from the Atlantic Coast of Morocco, has been evaluated for its influence on a mitogen-induced proliferation of human lymphocytes and growth of human tumor cell lines.

  7. 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.

  8. Results of The Analysis of The Blood Beryllium Lymphocyte Proliferation Test Data From The Oak Ridge Y-12 Study

    Energy Technology Data Exchange (ETDEWEB)

    Frome, EL

    2001-12-18

    The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. Newman [18] has discussed the clinical significance of the BeLPT and described a standard protocol that was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a ''stimulation index'' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the stimulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were considered in the early 1990's by Frome et al. [7]. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. The purposes of this report are to further evaluate the LAV method using new data, and to describe a new method for identification of an abnormal or borderline test. This new statistical biological positive (SBP) method reflects the clinical judgment that (1) at least two SIs show a ''positive'' response to beryllium, and (2), that the maximum of the six SIs must exceed a cut point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 facility in Oak Ridge and consist of 1080 worker and 33 nonexposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86

  9. Results of The Analysis of The Blood Beryllium Lymphocyte Proliferation Test Data From The Oak Ridge Y-12 Study

    Energy Technology Data Exchange (ETDEWEB)

    Frome, EL

    2001-12-18

    The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. Newman [18] has discussed the clinical significance of the BeLPT and described a standard protocol that was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a ''stimulation index'' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the stimulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were considered in the early 1990's by Frome et al. [7]. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. The purposes of this report are to further evaluate the LAV method using new data, and to describe a new method for identification of an abnormal or borderline test. This new statistical biological positive (SBP) method reflects the clinical judgment that (1) at least two SIs show a ''positive'' response to beryllium, and (2), that the maximum of the six SIs must exceed a cut point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 facility in Oak Ridge and consist of 1080 worker and 33 nonexposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86

  10. Colchicum autumnale agglutinin activates all murine T-lymphocytes but does not induce the proliferation of all activated cells.

    Science.gov (United States)

    Bemer, V; Van Damme, E J; Peumans, W J; Perret, R; Truffa-Bachi, P

    1996-08-25

    Plant lectins with mitogenic properties for T-lymphocytes have been particularly useful for the study of T-cell activation and effector functions. In the search for mitogenic lectins possessing activation features different from the ones associated with the already known mitogens, we found that an agglutinin isolated from Colchicum autumnale tubers, Colchicum autumnale agglutinin (CAA), possesses interesting properties. First, contrasting with the classical mitogens, CAA induces the proliferation of a fraction of the CD4+ and CD8+ mouse T-lymphocytes. Second, the CAA-induced proliferation requires MHC class II and CD4 molecules. Third, although only a fraction of T-cells enters into the cell cycle, all T-lymphocytes are activated and express high levels of the activation markers CD69 and CD44. Finally, CAA-stimulation is characterized by a particular pattern of the cytokine gene expression, reflected by the transcription of the IL2, IL5, and IFN-gamma genes, while the IL4 and IL10 genes remained silent. Taken together these data demonstrate that CAA activation does not conform to the pathway of T-cell triggering observed with classical mitogenes and represents a new tool for the analysis of T-cell activation.

  11. Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Peiwei, E-mail: pwxu@cdc.zj.cn; Lou, Xiaoming; Ding, Gangqiang, E-mail: gqding@cdc.zj.cn; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng, E-mail: zjcdcwxf@gmail.com

    2015-12-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β{sub 2}-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g{sup −1}, p < 0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g{sup −1}, p > 0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p < 0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p < 0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β{sub 2}-MG (p < 0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p < 0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released

  12. Ki-67 proliferation index in patients with placenta previa percreta in the third trimester.

    Science.gov (United States)

    Hilali, Nese; Kocarslan, Sezen; Vural, Mehmet; Incebiyik, Adnan; Camuzcuoglu, Aysun; Camuzcuoglu, Hakan

    2015-02-01

    The purpose of this study was to investigate proliferative capacity of placenta previa percreta in the third trimester via evaluating Ki-67 proliferating index. The paraffin blocks of placental tissues, which were obtained from the patients who underwent hysterectomy for placenta previa percreta (n = 12, gestational age > 28 weeks), from legal abortions (n = 12, gestational age  38 weeks), between January 2011 and April 2013, were included into the study. The paraffin blocks of the patients were stained with Ki-67 (proliferating cell marker) immunohistochemically, and Ki-67 proliferation index levels were calculated. Ki-67 proliferation index levels were higher in patients with legal abortions than patients with placenta percreta or noncomplicated cesarean delivery group. However, any statistically significant difference was not detected between the percreta and noncomplicated groups (p > 0.05). The tissue samples of the patients with placenta previa percreta exhibited low proliferative capacity similar to the samples of normal placentation group.

  13. Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset populations, cell proliferation and histological changes in avian lymphoid organs.

    Science.gov (United States)

    Girish, C K; Smith, T K; Boermans, H J; Anil Kumar, P; Girgis, G N

    2010-10-01

    An experiment was conducted to investigate the effects of dietary Fusarium mycotoxins on gut immunity, cell proliferation, and histology of avian lymphoid organs. The efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) was also determined. Seventy-two one-day-old male turkey poults were fed corn, wheat, and soybean meal-based diets for 21 days. Diets included control grains, contaminated grains and contaminated grains +0.2% GMA. The major contaminant was deoxynivalenol (3.9 μg/g) with lesser amounts of zearalenone (0.67-0.75 μg/g), 15-acetyl-deoxynivalenol (0.34 μg/g) and HT-2 toxin (0.078-0.085 μg/g). T- and B-lymphocyte populations and crypt cellular proliferation in duodenum, jejunum, ileum and cecal tonsil were measured immunohistochemically on day 14 and 21. Histological changes were recorded after 14 and 21 days of feeding. Feeding contaminated grains significantly increased the percentage of B-lymphocytes in ileum on day 14, and reduced (Pcontaminated diets also caused a reduction (Pcontaminated with Fusarium mycotoxins results in adverse effects on gut immunity and mucosal cell proliferation.

  14. Strong additive effect of calcitriol and cyclosporine A on lymphocyte proliferation in vitro and rat liver allotransplantations in vivo

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ai-bin; ZHENG Shu-sen

    2006-01-01

    Background Vitamin D3 and its metabolites have been found to exert immunosuppressive effects both in vivo and in vitro. We investigated the synergistic effect of calcitriol and cyclosporine A (CsA) on lymphocyte proliferation in vitro and graft rejection following rat liver allotransplantations in vivo.Methods Alloantigen driven, human peripheral mononuclear cells' proliferation and cytokine production capacity were tested in the presence or absence of various concentrations of calcitriol or CsA. In vivo, liver allografts were transplanted in a high responder strain combination (SD to Wistar) rats and combination of subtherapeutical dose of CsA and calcitriol was administered in recipients, whereas the control recipients received single or no immunosuppressant. Proliferation of splenocyte from recipient was tested with mixed lymphocyte reaction. Serum interleukin-2 (IL-2) and interferon gamma (IFN-γ) concentrations were measured with enzyme linked immunosorbent assay.Results Combined medication of 10-9 mol/L calcitriol and 100 ng/ml CsA inhibited human peripheral mononuclear cells' proliferation to alloantigen and the production of IL-2 and IFN-γ but promoted that of IL-4and IL-10. Similarly, combination of 250 ng· kg-1 · d-1 calcitriol and 1.0 mg · kg-1 · d-1 CsA showed an additive effect in liver transplant model. It restrained splenocyte proliferation to alloantigen from donor and significantly reduced serum concentration of IL-2 and IFN-γ in recipients. Consequently, allograft rejection in combined medication group was minor (median William's grade was 1.0 vs 3.0 in combined medication group and in the control group, P<0.05) and the recipients' survival was evidently prolonged [(93.7±5.8) days vs (12.6±1.4) days in combined medication group and in the control group, P<0.01].Conclusion A combination of calcitriol and CsA has an additive effect on limiting lymphocyte proliferation and prolonging liver graft survival. With its additional

  15. [Preparation of polyclonal antibody against sAPRIL and analysis of function in suppressing sAPRIL-mediated lymphocyte proliferation].

    Science.gov (United States)

    Du, Ben-Jun; Gao, Quan-Sheng; Lan, Zhi; Fan, Jun-Wen; Ding, Lu-Jing; Li, Min; Qi, Yuan-Yuan; Kong, Wei

    2011-08-01

    This study was aimed to prepare the polyclonal antibody against the soluble proliferation-inducing ligand (sAPRIL) antigen and to investigate its effects in suppressing sAPRIL mediated lymphocyte proliferation. Mutated recombinant sAPRIL protein, which lacks biological activity but maintains immunogenicity, was used as antigen to immunize humanized SCID mice. Sera were obtained at 6 weeks after immunization. Indirect ELISA and Western blot were used to detect the antibody titer and specificity. The inhibition of polyclonal antibodies on Raji and Jurkat cell proliferation stimulated by sAPRIL was assessed by the MTT assay. The results showed that the mutant of sAPRIL could induce the production of polyclonal antibodies against human sAPRIL. Western blot and indirect ELISA analyses indicated that the anti-serum had higher specificity with a titer of 1:640. Functional analysis revealed that these polyclonal antibodies significantly inhibited the proliferation of Raji and Jurkat cell stimulated by sAPRIL (p polyclonal antibody against human sAPRIL is successfully prepared, which can inhibit the proliferation of Raji and Jurkat cells stimulated by sAPRIL in vitro.

  16. Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens.

    Science.gov (United States)

    Guo, Qingyun; Wang, Zixu; Dong, Yulan; Cao, Jing; Chen, Yaoxing

    2017-06-28

    Previous study has demonstrated that melatonin plays a critical role in monochromatic-light-induced lymphocyte proliferation in response to T cell mitogen concanavalin A (ConA). However, its intracellular mechanism is still unclear. In this study, we investigate the intracellular signal pathways of melatonin receptor-mediated T-lymphocyte proliferation in the spleens of chicks exposed to different light wavelengths. Results showed that green light enhanced T-lymphocyte proliferation by 2.46-6.83% and increased splenic mRNA and protein expressions of melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) by 16.05-40.43% compared with the white, red and blue light groups. However, pinealectomy resulted in a decrease in T-lymphocyte proliferation and melatonin receptor expression with no statistically significant differences between the different light groups. In vitro experiments showed that the Mel1b selective antagonist 4P-PDOT, the Mel1c selective antagonist prazosin and the mitogen-activated protein kinase kinase-1 (MEK-1) inhibitor PD98059 suppressed both melatonin-induced lymphocyte proliferation in response to ConA and melatonin- and ConA-stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) activity but that the Mel1a/Mel1b non-selective antagonist luzindole did not. In addition, pretreatment with forskolin (FSK, the adenylyl cyclase activator), H89 (the PKA inhibitor), U73122 (the PLC inhibitor) or Go6983 (the broad spectrum PKC inhibitor) markedly attenuated melatonin- and ConA-stimulated T-lymphocyte proliferation and ERK1/2 activity. These results demonstrate that melatonin mediates green-light-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors by triggering crosstalk between the cAMP/PKA and PLC/PKC signal pathways followed by ERK1/2 activation.

  17. Lymphocytic alveolitis: A surprising index of poor prognosis in patients with primary Sjogren's syndrome.

    Science.gov (United States)

    Dalavanga, Y A; Voulgari, P V; Georgiadis, A N; Leontaridi, C; Katsenos, S; Vassiliou, M; Drosos, A A; Constantopoulos, S H

    2006-07-01

    Twelve years ago we reported that lymphocytic alveolitis [or bronchoalveolar lavage (BAL) lymphocytosis] correlates with clinical pulmonary involvement in primary Sjogren's syndrome (pSS). Our thesis was based on subtle clinical and functional evidence of interstitial lung disease (ILD) in pSS patients with "high lymphocytic alveolitis" (>15% lymphocytes in BAL). This report is a follow-up study of these patients. Basic clinical and functional re-evaluation of the 22 patients with pSS, studied in 1991, emphasized the differences between those with alveolitis and those without alveolitis. There was no significant functional decline. There were, however, two statistically significant differences between the two groups: (1) only patients with BAL lymphocytosis had to be treated with steroids (5/12 vs. 0/10, P < 0.05) and (2) only patients with BAL lymphocytosis had died in the mean time (6/12 vs. 0/10, P < 0.01). The causes of death were various. On only two occasions were they related to respiratory infections while there were no deaths from respiratory failure secondary to ILD. BAL lymphocytosis appears to be a surprisingly serious index of dismal prognosis in patients with pSS. We offer no unifying pathophysiologic mechanism for it and, therefore, all we propose is that BAL is performed early, in as many patients with pSS as possible. These patients should then be followed up systematically, in order to evaluate if BAL lymphocytosis has any pathophysiologic importance in the development of clinically serious pSS, which is serious enough to lead to death.

  18. Autoantigenic targets of B-cell receptors derived from chronic lymphocytic leukemias bind to and induce proliferation of leukemic cells.

    Science.gov (United States)

    Zwick, Carsten; Fadle, Natalie; Regitz, Evi; Kemele, Maria; Stilgenbauer, Stephan; Bühler, Andreas; Pfreundschuh, Michael; Preuss, Klaus-Dieter

    2013-06-06

    Antigenic targets of the B-cell receptor (BCR) derived from malignant cells in chronic lymphocytic leukemia (CLL) might play a role in the pathogenesis of this neoplasm. We screened human tissue-derived protein macroarrays with antigen-binding fragments derived from 47 consecutive cases of CLL. An autoantigenic target was identified for 12/47 (25.5%) of the cases, with 3 autoantigens being the target of the BCRs from 2 patients each. Recombinantly expressed autoantigens bound specifically to the CLL cells from which the BCR used for the identification of the respective autoantigen was derived. Moreover, binding of the autoantigen to the respective leukemic cells induced a specific activation and proliferation of these cells. In conclusion, autoantigens are frequent targets of CLL-BCRs. Their specific binding to and induction of proliferation in the respective leukemic cells provide the most convincing evidence to date for the long-time hypothesized role of autoantigens in the pathogenesis of CLL.

  19. Interaction between Cl- channels and CRAC-related Ca2+ signaling during T lymphocyte activation and proliferation

    Institute of Scientific and Technical Information of China (English)

    Guan-lei WANG; Yan QIAN; Qin-ying QIU; Xiu-jian LAN; Hua HE; Yong-yuan GUAN

    2006-01-01

    Aim:To test the hypothesis that Cl- channel blockers affect T cell proliferation through Ca2+-release-activated Ca2+ (CRAC) signaling and examine the effects of the combination of a CRAC channel blocker and a Cl- channel blocker on concanavalin A (ConA;5 mg/mL) -induced Ca2+ signaling,gene expression and cellular proliferation in human peripheral T lymphocytes.Methods:[3H]Thymidine incorporation,Fura-2 fluorescent probe,RNase protection assay,and reverse transcription.polymerase chain reaction were used.Results:The Cl- channel blocker 4,4'-diisothiocvanostilbene-2,2'-disulfonic acid (DIDS) inhibited ConA-induced Ca2+influx.interleukin-2 mRNA expression and T lymphocyte proliferation in a concentration.dependent manner,and also enhanced the inhibitory effects of 1-{beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl}-1H-imidazole (SK&F96365) on the above key events during T cell activation.A combination ofDIDS (1μmol/L) and SK&F96365 (1μmol/L) significantly diminished ConA-induced ClC-3 mRNA expression by 64%,whereas DIDS (1μmol/L) or SK&F96365 (1μmol/L) alone decreased ConA-induced ClC-3 mRNA expression by only 16% and 9%.respectively.Conclusion:These results suggest that there is an interaction between CRAC-mediated Ca2+ signaling and DIDS-sensitive C1-channels during ConA-induced T cell activation and proliferation.Moreover,the DIDS-sensitive Cl-channels may be related to the ClC-3 Cl- channels.

  20. Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae

    Science.gov (United States)

    Kuo, Y C; Weng, S C; Chou, C J; Chang, T T; Tsai, W J

    2003-01-01

    Effects of ergosterol peroxide (C28H44O3; Cpd 6A) from Cordyceps cicadae on phytohemagglutinin (PHA)-stimulated cell proliferation were studied in primary human T cells. The results showed that Cpd 6A suppressed T-cell proliferation for about 24 h after stimulation with PHA. Cell cycle analysis indicated that Cpd 6A arrested the cell cycle progression of activated T cells from the G1 transition to the S phase. To localize the point in the cell cycle where arrest occurred, a set of key regulatory events leading to the G1/S boundary, including the expression of cyclins D2, E, A1, and B1, interleukin (IL)-2, IL-4, interferon-γ (IFN-γ), and activating protein-1 (AP-1), was examined. Cpd 6A suppressed, in activated T lymphocytes, the production and mRNA expression of cyclin E, IL-2, IL-4, IL-10, and IFN-γ in a dose-dependent manner. Expression of AP-1 proteins, consisting of c-Fos and c-Jun, in activated T lymphocytes was decreased by Cpd 6A. The kinetic study indicated that the inhibitory effects of Cpd 6A on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. T-cell proliferation after Cpd 6A treatment was partially restored by addition of IL-2, IL-4, and IFN-γ. These suppressant effects of Cpd 6A on T-cell proliferation, activated by PHA, appeared to be mediated, at least in part, through the inhibition of early gene transcripts, especially those of cyclin E, IFN-γ, IL-2, and IL-4, and by arresting cell cycle progression in the cells. PMID:14504132

  1. [Cultured epidermis in the treatment of leg ulcer: "edge effect" and correlation with keratinocyte proliferation index].

    Science.gov (United States)

    Giannotti, V; Pimpinelli, N; Mariotti, V; Borgognoni, L; Reali, U M

    1990-04-01

    Cultured keratinocyte grafting (KG) of chronic leg ulcers produces an impressive stimulation of host epithelization by an effect on the edge of the ulcer, which starts to grow in rapidly ("edge effect"). In 5 patients with chronic leg ulcers treated by KG, we have studied the proliferation index of the epidermis of the edge and of the graft area and that of secondary culture keratinocytes. The aim of the study was to correlate this parameter with the clinical evolution of the treated lesions. We found a significant correlation between the proliferation index of the edge epidermis and the clinical evidence of "edge effect".

  2. Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes.

    Directory of Open Access Journals (Sweden)

    Linxi Qian

    Full Text Available Alkylglycerols (AKGs are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg. Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL transcription of IgG (γ1 mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1/GATA-3 (Th2 flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2. It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1 and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10 were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.

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

    OpenAIRE

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

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) st...

  4. Leukemia cell proliferation and death in chronic lymphocytic leukemia patients on therapy with the BTK inhibitor ibrutinib.

    Science.gov (United States)

    Burger, Jan A; Li, Kelvin W; Keating, Michael J; Sivina, Mariela; Amer, Ahmed M; Garg, Naveen; Ferrajoli, Alessandra; Huang, Xuelin; Kantarjian, Hagop; Wierda, William G; O'Brien, Susan; Hellerstein, Marc K; Turner, Scott M; Emson, Claire L; Chen, Shih-Shih; Yan, Xiao-Jie; Wodarz, Dominik; Chiorazzi, Nicholas

    2017-01-26

    BACKGROUND. Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. METHODS. We used stable isotopic labeling with deuterated water ((2)H2O) to measure directly the effects of ibrutinib on leukemia cell proliferation and death in 30 patients with CLL. RESULTS. The measured average CLL cell proliferation ("birth") rate before ibrutinib therapy was 0.39% of the clone per day (range 0.17%-1.04%); this decreased to 0.05% per day (range 0%-0.36%) with treatment. Death rates of blood CLL cells increased from 0.18% per day (average, range 0%-0.7%) prior to treatment to 1.5% per day (range 0%-3.0%) during ibrutinib therapy, and they were even higher in tissue compartments. CONCLUSIONS. This study provides the first direct in vivo measurements to our knowledge of ibrutinib's antileukemia actions, demonstrating profound and immediate inhibition of CLL cell proliferation and promotion of high rates of CLL cell death. TRIAL REGISTRATION. This trial was registered at clinicaltrials.gov (NCT01752426). FUNDING. This study was supported by a Cancer Center Support Grant (National Cancer Institute grant P30 CA016672), an NIH grant (CA081554) from the National Cancer Institute, MD Anderson's Moon Shots Program in CLL, and Pharmacyclics, an AbbVie company.

  5. Novel T lymphocyte proliferation assessment using whole mouse cryo-imaging

    Science.gov (United States)

    Wuttisarnwattana, Patiwet; Raza, Syed A.; Eid, Saada; Cooke, Kenneth R.; Wilson, David L.

    2014-03-01

    New imaging technologies enable one to assess T-cell proliferation, an important feature of the immunological response. However, none of the traditional imaging modalities allow one to examine quantiatively T-cell function with microscopic resolution and single cell sensitivity over an entire mouse. To address this need, we established T-cells proliferation assays using 3D microscopic cryo-imaging. Assays include: (1) biodistribution of T-cells, (2) secondary lymphoid organ (SLO) volume measurement, (3) carboxyfluorescein succinimidyl ester (CFSE) dilution per cell as cells divide. To demonstrate the application, a graft-versus-host-disease (GVHD) model was used. 3D visualization show that T-cells specifically homed to the SLOs (spleen and lymph nodes) as well as GVHD target organs (such as GI-tract, liver, skin and thymus).The spleen was chosen as representative of the SLOs. For spleen size analysis, volumes of red and white pulp were measured. Spleen volumes of the allogeneic mice (with GVHD) were significantly larger than those of the syngeneic mice (without GVHD) at 72 to 120 hours post-transplant. For CFSE dilution approach, we employed color-coded volume rendering and probability density function (PDF) of single cell intensity to assess T-cell proliferation in the spleen. As compared to syngeneic T-cells, the allogeneic T-cells quickly aggregated in the spleen as indicated by increasing of CFSE signal over the first 48 hours. Then they rapidly proliferated as evidenced by reduced CFSE intensity (at 48-96 hours). Results suggest that assays can be used to study GVHD treatments using T-cell proliferation and biodistibution as assays. In summary, this is the first time that we are able to track and visualize T-cells in whole mouse with single cell sensitivity. We believe that our technique can be an alternative choice to traditional in vitro immunological proliferation assays by providing assessment of proliferation in an in vivo model.

  6. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients

    DEFF Research Database (Denmark)

    Peev, N A; Tonchev, A B; Penkowa, M

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... within 2 months of the excision in patients with uncontrolled systemic disease and not subjected to adjuvant whole brain radio-therapy. MATERIALS AND METHODS: Tissue biopsies derived from 25 patients with brain metastases specifically selected to be a single totally resected lesion and not treated...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing...

  7. CD8+T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever

    OpenAIRE

    Andréia Manso de Matos; Karina Inacio Carvalho; Daniela Santoro Rosa; Lucy Santos Villas-Boas; Wanessa Cardoso da Silva; Célia Luiza de Lima Rodrigues; Olímpia Massae Nakasone Peel Furtado Oliveira; José Eduardo Levi; Evaldo Stanislau Affonso de Araújo; Claudio Sergio Pannuti; Expedito José Albuquerque Luna; Esper George Kallas

    2015-01-01

    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood m...

  8. Damage of Splenic T Lymphocyte Proliferation and Differentiation and Its Normalization by Electroacupuncture in Morphine-Dependent Mice Mode

    Directory of Open Access Journals (Sweden)

    Hong-Yu Li

    2011-01-01

    Full Text Available In a previous paper we reported that electroacupuncture (EA could suppress opioid withdrawal syndrome and increase the appetite, sleep, and body weight in heroin addicts or morphine dependent animals. Considering that opioids were known to inhibit immune function, the present study was designed to observe whether EA could modulate the immune status of morphine dependent and withdrawal mice. We found that chronic morphine-induced decrease of splenic T lymphocyte proliferation and IL-2 production can be significantly raised by 2 Hz EA, and the fluctuation of CD4+/CD8+ ratio was also run to the baseline level by the EA. These findings indicated that chronic morphine exposure-induced immune dysfunction in mice could be normalized by 2 Hz EA.

  9. Proliferation capacity of T-lymphocytes is affected transiently after a long-term weight gain in Beagle dogs.

    Science.gov (United States)

    Van de Velde, H; Janssens, G P J; Rochus, K; Duchateau, L; Scharek-Tedin, L; Zentek, J; Nguyen, P; Cox, E; Buyse, J; Biourge, V; Hesta, M

    2013-04-15

    Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

  10. Thymus derived inhibitor of lymphocyte proliferation : III—Partial purification and characteristic biological activity

    NARCIS (Netherlands)

    Rijke, E.O.; Ballieux, R.E.

    1980-01-01

    A crude factor isolated from bovine thymus was partially purified using ion exchange chromatography. The resulting fraction was tested for inhibitory properties towards the proliferation of various human and murine lymphoid cells in culture. It was found that this partially purified thymic factor (T

  11. A Compartmental Model for Computing Cell Numbers in CFSE-based Lymphocyte Proliferation Assays

    Science.gov (United States)

    2012-01-31

    proliferation, survival and differentiation using CFSE time-series data, Nature Protocols , 2 (2007), 2057–2067. [41] E.D. Hawkins, J.F. Markham, L.P...the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester, Nature Protocols , 2 (2007), 2049– 2056. [61] P. Revy, M. Sospedra

  12. CD8+ T lymphocyte expansion, proliferation and activation in dengue fever.

    Science.gov (United States)

    de Matos, Andréia Manso; Carvalho, Karina Inacio; Rosa, Daniela Santoro; Villas-Boas, Lucy Santos; da Silva, Wanessa Cardoso; Rodrigues, Célia Luiza de Lima; Oliveira, Olímpia Massae Nakasone Peel Furtado; Levi, José Eduardo; Araújo, Evaldo Stanislau Affonso; Pannuti, Claudio Sergio; Luna, Expedito José Albuquerque; Kallas, Esper George

    2015-02-01

    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.

  13. CD8+ T lymphocyte expansion, proliferation and activation in dengue fever.

    Directory of Open Access Journals (Sweden)

    Andréia Manso de Matos

    2015-02-01

    Full Text Available Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.

  14. CD8+ T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever

    Science.gov (United States)

    de Matos, Andréia Manso; Carvalho, Karina Inacio; Rosa, Daniela Santoro; Villas-Boas, Lucy Santos; da Silva, Wanessa Cardoso; Rodrigues, Célia Luiza de Lima; Oliveira, Olímpia Massae Nakasone Peel Furtado; Levi, José Eduardo; Araújo, Evaldo Stanislau Affonso; Pannuti, Claudio Sergio; Luna, Expedito José Albuquerque; Kallas, Esper George

    2015-01-01

    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population. PMID:25675375

  15. Correlation of apparent diffusion coefficient with Ki-67 proliferation index in grading meningioma.

    Science.gov (United States)

    Tang, Yi; Dundamadappa, Sathish K; Thangasamy, Senthur; Flood, Thomas; Moser, Richard; Smith, Thomas; Cauley, Keith; Takhtani, Deepak

    2014-06-01

    A noninvasive method to predict aggressiveness of high-grade meningiomas would be desirable because it would help anticipate tumor recurrence and improve tumor management and the treatment outcomes. The Ki-67 protein is a marker of tumor proliferation, and apparent diffusion coefficient (ADC) is related to tumor cellularity. Therefore, we sought to determine whether there is a statistically significant correlation between ADC and Ki-67 values in meningiomas and whether ADC values can differentiate various meningioma subtypes. MRI examinations and histopathology of 68 surgically treated meningiomas were retrospectively reviewed. Mean ADC values were derived from diffusion imaging. Correlation coefficients were calculated for mean ADC and Ki-67 proliferation index values using linear regression. An independent unpaired Student t test was used to compare the ADC and Ki-67 proliferation index values from low-grade and more aggressive meningiomas. A statistically significant inverse correlation was found between ADC and Ki-67 proliferation index for low-grade and aggressive meningiomas (r(2) = -0.33, p = 0.0039). ADC values (± SD) of low-grade meningiomas (0.84 ± 0.14 × 10(-3) mm(2)/s) and aggressive (atypical or anaplastic) meningiomas (0.75 ± 0.03 × 10(-3) mm(2)/s) were significantly different (p = 0.0495). Using an ADC cutoff value of 0.70 × 10(-3) mm(2)/s, the sensitivity for diagnosing aggressive meningiomas was 29%, specificity was 94%, positive predictive value was 67%, and negative predictive value was 75%. ADC values correlate inversely with Ki-67 proliferation index and help differentiate low-grade from aggressive meningiomas.

  16. Cytotoxicity and Inhibition of Lymphocyte Proliferation of Fasciculatin, a Linear Furanosesterterpene Isolated from Ircinia variabilis Collected from the Atlantic Coast of Morocco

    Directory of Open Access Journals (Sweden)

    Werner Herz

    2005-03-01

    Full Text Available Abstract: Fasciculatin, a furanosesterterpene isolated from the marine sponge Ircinia variabilis from the Atlantic Coast of Morocco, has been evaluated for its influence on a mitogen-induced proliferation of human lymphocytes and growth of human tumor cell lines.

  17. Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

    Directory of Open Access Journals (Sweden)

    Ochoa-Hernández Alejandra B

    2012-02-01

    Full Text Available Abstract Background WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the WNT7A gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation. Methods We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL, and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR analysis were performed to determine relative WNT7A expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures. Results WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p ≤0.001. By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway. Conclusions To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible

  18. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization.

    Science.gov (United States)

    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-12-15

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P SII scores (P SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice.

  19. Degree of tumor FDG uptake correlates with proliferation index in triple negative breast cancer.

    Science.gov (United States)

    Tchou, Julia; Sonnad, Seema S; Bergey, Meredith R; Basu, Sandip; Tomaszewski, John; Alavi, Abass; Schnall, Mitchell

    2010-12-01

    2-Deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake may be a useful surrogate marker for proliferation index, but the correlation has not always been clear-cut. Previous research by our group suggests that FDG-positron emission tomography (PET) is sensitive in detecting triple negative breast cancer. We therefore performed a pilot study to test if FDG uptake correlated with proliferation index in women with triple negative cancer. To determine whether proliferation index correlates with metabolic uptake of FDG in women with triple negative breast cancer, we performed a retrospective analysis correlating %Ki67 nuclear stain with tumor maximum standardized uptake values (SUVmax) in a group of 41 women, 22 with triple negative and 19 with non-triple negative breast cancer. As expected, [18F]-PET imaging was significantly more sensitive in detecting triple negative breast cancer than non-triple negative breast cancer, 95.5% vs 68.4% (p = 0.036). In general, SUVmax and %Ki67 nuclear stain values rise as histologic grade worsens. Histologic grade of triple negative breast cancer was more often poorly differentiated than non-triple negative cancer (p = 0.001). SUVmax correlated with %Ki67 nuclear staining in our entire cohort (spearman correlation = 0.485, p = 0.002). Moreover, this significant correlation appeared to be driven primarily by a subset of women with triple negative cancer (spearman correlation = 0.497, p = 0.019). Degree of tumor FDG uptake correlated significantly with proliferation index in women with triple negative breast cancer suggesting a potential role of FDG-PET in treatment response monitoring for this group of women. Future studies are necessary to define the role of PET imaging as a non-invasive means to monitor breast cancer treatment response in the neoadjuvant setting.

  20. Cytokine production and lymphocyte proliferation in patients with Nocardia brasiliensis actinomycetoma.

    Science.gov (United States)

    Méndez-Tovar, Luis J; Mondragón-González, Rafael; Vega-López, Francisco; Dockrell, Hazel M; Hay, Roderick; López-Martínez, Rubén; Manzano-Gayosso, Patricia; Hernández-Hernández, Francisca; Padilla-Desgarennes, Carmen; Bonifaz, Alexandro

    2004-11-01

    IFN-gamma, TNF-alpha, IL-4, IL-10 and IL-12 concentrations in the supernatant of peripheral blood mononuclear cell (PBMC) cultures and the in vitro proliferation of PBMC were studied in 25 patients with actinomycetoma caused by Nocardia brasiliensis and in 10 healthy controls from endemic zones. Cell cultures were stimulated by a N. brasiliensis crude cytoplasmic antigen (NB) and five semi-purified protein fractions (NB2, NB4, NB6, NB8, and NB10) separated by isoelectric. Phytohemagglutinin (PHA) and purified protein derivative (PPD) of Mycobacterium tuberculosis were used as control antigens. Skin tests were performed by injecting 0.1 ml of candidin and PPD intradermally (ID). Patients showed a poor response to tuberculin, while their response to candidin was more than two fold greater than that observed in the controls. Cell proliferation showed no statistically significant differences in either group. IFN-gamma production was higher in the healthy controls than in the patients, whereas TNF-alpha secretion was slightly higher in the patients' cultures. IL-4 was detected in the patients' cultures but not in the controls. IL-10 and IL-12 were present at low concentrations in both groups. These results suggest that patients with actinomycetoma show normal antigen recognition, but with low IFN-gamma production, and higher concentrations of IL-4, IL-10 and TNF-alpha in the patients' PBMC cultures, indicating that they probably have a Th2 type of immune response.

  1. Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Purvina, Maija; Hoste, Astrid; Rossignol, Jean-Michel [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France); Lagaudriere-Gesbert, Cecile, E-mail: cecile.lagaudriere-gesbert@u-psud.fr [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer P20, precursor of the HBeAg, interacts with the cellular protein gC1qR. Black-Right-Pointing-Pointer HBeAg and P20 bind to T cell surface and inhibit mitogen-induced T cell division. Black-Right-Pointing-Pointer HBeAg and P20 inhibition of T cell proliferation is gC1qR and IL-1RAcP-independent. -- Abstract: The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).

  2. AKRs expression in peripheral blood lymphocytes from smokers: the role of body mass index.

    Science.gov (United States)

    Barrón-Vivanco, B S; Rothenberg, S J; Medina-Díaz, I M; Robledo-Marenco, L; Rojas-García, A E; Hernández-Cadena, L; Poblete-Naredo, I; Elizondo, G; Albores, A

    2013-04-01

    Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage. Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals. Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs). The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1*2 and AKR1C3*2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels in PBLs from smokers. In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index (BMI) less than 25. However, AKR1A1*2 and AKR1C3*2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3 mRNA levels. These results suggest that AKRs induction by PAHs in smokers' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs' effects needs further investigation.

  3. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  4. Anchoring of c-myc on nuclear matrix proteins in process of mouse thymic T lymphocyte proliferation induced by ConA

    Institute of Scientific and Technical Information of China (English)

    曾丛梅; 蔡树涛; 周凤兰; 张锦珠; 王平

    1996-01-01

    Isolation and characteriation of functional nudear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nudear matrix research. Southwestern blotting (DNA-protein hybridization) was applied to studying the anchoring of c-myc on the nudear matrix proteins in mouse thymic T lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36 nudear matrix proteins specifically. In the process of mouse thymic PNA T lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36 nudear matrix proteins changed dynamically.

  5. Effects of the protein kinase C stimulant bryostatin 1 on the proliferation and colony formation of irradiated human T-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Sung, S.J.; Lin, P.-S.; Schmidt-Ullrich, R.; Hall, C.E.; Walters, J.A.; McCrady, C.; Grant, S. [Virginia Commonwealth Univ., Richmond, VA (United States)

    1994-12-01

    The protein kinase C stimulant bryostatin 1 (Bryo) was used in examining human peripheral blood T-lymphocyte radiosensitivities in proliferation assays. Bryo was similar to PMA in inducing T-cell proliferation by the CD3, CD28 and CD69 pathways. No difference in radiosensitivities was observed in T-cells stimulated by the three independent surface antigen-mediated activation pathways. CD3 was chosen as the second signal for comparing the potencies of the three different first signals Bryo, phorbol 12-myristate, 13-acetate (PMA), and interleukin 2 (IL-2) in stimulating T-cell proliferation and in maintaining this response after radiation. Though there were radioresponse differences among various individuals, the irradiated lymphocytes consistently showed significantly greater proliferation when treated with Bryo or PMA than with IL-2. These results support the important tole of protein kinase C in T-cell radiation responses, and suggest a potential role for Bryo in enhancing T-lymphocyte survival during radiation therapy. (author).

  6. A novel lectin from Artocarpus lingnanensis induces proliferation and Th1/Th2 cytokine secretion through CD45 signaling pathway in human T lymphocytes.

    Science.gov (United States)

    Cui, Bo; Li, Lu; Zeng, Qiyan; Lin, Faquan; Yin, Lijun; Liao, Liejun; Huang, Min; Wang, Jingping

    2017-04-01

    Lectins are carbohydrate-binding proteins and have been used for purification and characterization of glycoproteins. In this study, a novel 58.9-kDa tetrameric lectin from Artocarpus lingnanensis seeds was purified, characterized, and its mitogenic potential was evaluated. The hemagglutination inhibition assay indicated that Artocarpus lingnanensis lectin (ALL) showed specificity toward galactose. ALL was effectively purified in a single-step using affinity chromatography on a galactose-Sepharose column. ALL showed pH optima between 5.0 and 9.0, and optimal temperature between 20 and 40 °C. ALL triggered proliferation and activation of human T lymphocytes (e.g., CD4(+) T lymphocytes). Flow cytometry and laser scanning confocal microscopy revealed binding of ALL to T cells and colocalized with CD45. Affinity chromatography and Western blot suggested that CD45 isolated from human T cell membrane fraction may be the major receptor of ALL. CD45 blocking antibody attenuated the binding and proliferation of T cells induced by ALL. CD45-PTPase inhibitor dephostatin reduced ALL-induced T cells proliferation and expression of CD25 and pZAP-70. Furthermore, secretion of ALL-induced Th1/Th2 cytokines was blocked with dephostatin. Also, dephostatin inhibited phosphorylation of ALL-mediated activation of ERK and p38MAPK. This study demonstrates the involvement of CD45-mediated signaling in ALL-induced T lymphocyte proliferation and Th1/Th2 cytokine secretion through activation of p38 and ERK.

  7. Recombinant human B7-H4 expressed in Escherichia coli inhibits T lymphocyte proliferation and IL-2 secretion in vitro

    Institute of Scientific and Technical Information of China (English)

    Yi-xiang MAO; Xue-guang ZHANG; Yong-Jing CHEN; Van GE; Hong-bing MA; Jian-feng YU; Hong-ya WU; Yu-min HU; Qin WANG; Qin SHI

    2006-01-01

    Aim: To explore the biofunctions of human B7-H4 generated from prokaryotic system. Methods: The gene of human B7-H4 extracellular region (IgⅤ-like and IgC-like domains) was obtained by PCR from human cDNA FLJ22418 and then inserted into the prokaryotic expression vector pGEX-5X-3 expressing glutathione. r-transferase (GST) fusion protein. After being identified by restriction enzyme digestion and sequencing, the recombinant vector was transferred into host strain E coli BL21-RIL(DE3). A 47 kDa fusion protein (GST/hB7-H4) was induced by isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified by standard methods reported in the prokaryotic system. The inhibitory effect of GST/hB7-H4 on proliferation of T cells was observed in vitro by CD3mAb activated T-cell cultur-ing system and [3H]-thymidine incorporation assay. The concentrations of interleukin-2 and iterferon-g in the supernatants of T cells were determined by ELISA. Results: We successfully constructed the method for high-level expression and purification of the hB7-H4 extracellular domain as GST fusion protein from E coli. The GST/hB7-H4 fusion protein produced in bacteria had obvious biological activity to inhibit T-lymphocyte proliferation and IL-2 secretion. Conclusion: The prokaryote expression system could be used to generate hB7-H4 protein with natural spatial conformations and biological functions, which provided an efficient and economical way for the preparation of this target protein.

  8. 黑素细胞对同种异体淋巴细胞转化增殖的影响%The effects of Melanocyte to the Transormation and Proliferation of Allogeneic Lymphocyte

    Institute of Scientific and Technical Information of China (English)

    项蕾红; 郑志忠; 陈伟华; 祝绿川; 廖康煌

    2001-01-01

    目的观察体外培养人黑素细胞与同种异体的淋巴细胞混合后,黑素细胞对淋巴细胞的促转化、增殖作用。方法用3H-TdR掺入同位素液态闪烁计数法测定淋巴细胞的转化增殖率。实验结果应用t检验进行统计学分析。结果黑素细胞对同种异体淋巴细胞的转化增殖率与刀豆蛋白(conA)刺激淋巴细胞转化、增殖的阳性对照比较,结果显示黑素细胞的促淋巴细胞转化、增殖的特异性抗原作用较弱。进一步比较黑素细胞对不同病期的白癜风患者的淋巴细胞的影响,发现黑素细胞对活动期白癜风患者淋巴细胞的刺激作用相对较强,而稳定期患者和正常人对照组结果无显著性差异。结论正常人黑素细胞的特异性抗原作用较弱,为同种异体黑素细胞移植治疗白癜风创造了有利的条件。%Objective To observe the cultured melanocyte,as specificantigen,how to affect the transormation and proliferation of allogeneic lymphocytes in the mixed melanocyte lymphocyte reaction.Methods 3H-thymicine-added uptake was evaluated by means of liquid scintillation counting and expressed as cpm.The Results of lymphocyte proliferation were expressed by the stimulation indexes.The indexes of each group was analyzed statistically by t-test.Results The stimulation indexes of active vitiligo was significantly different compared with that of stable vitiligo and normal controls.The stimulation indexes of the group which melanocyte was used as specific antigen,was also significantly different compared with that of positive controls.Conclusion The melanocyte worked as specific antigen in mixed melanocyte lymphocyte reaction and its effect was weak.In the melanocyte allograft,the patients with stable vitiligo were the first choice.

  9. Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Massimo Giuliani

    Full Text Available Human bone marrow mesenchymal stem cells (BM-MSC are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK cells, Dendritic Cells (DC, and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb, cyclins A and D1, as well as up-regulating p27(kip1 expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low/CD8(low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.

  10. Estudo da proliferação linfocitária em pacientes sensibilizados ao níquel Study on lymphocyte proliferation in nickel sensitive patients

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    Ana Paula Galli Sanchez

    2005-04-01

    concentrations of Candida albicans antigen as well as pokeweed, phytohemagglutinin A and anti-CD3 antibody (OKT3 mitogens. Tritiated thymidine was added to plates, radioactivity incorporated by cells was measured and the results expressed by the stimulation index (SI. RESULTS: The lymphocyte proliferative response was higher in cases than in controls in all nickel concentrations tested. Considering positive test reactions when SI > 3, none of the controls and 16 (84.21% cases were positive in at least one of five concentrations used. The proliferative responses to Candida albicans and mitogens were similar in cases and controls, demonstrating normal cellular immunity in both groups. CONCLUSION: The lymphocyte proliferation test is useful in diagnosis of nickel sensitivity.

  11. Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro.

    Directory of Open Access Journals (Sweden)

    Lynn B Williams

    Full Text Available Multipotent mesenchymal stromal cells (MSC are receiving increased attention for their non-progenitor immunomodulatory potential. Cryopreservation is commonly used for long-term storage of MSC. Post-thaw MSC proliferation is associated with a lag-phase in vitro. How this lag-phase affect MSC immunomodulatory properties is unknown. We hypothesized that in vitro there is no difference in lymphocyte suppression potential between quick-thawed cryopreserved equine cord blood (CB MSC immediately included in mixed lymphocyte reaction (MLR and same MSC allowed post-thaw culture time prior to inclusion in MLR. Cryopreserved CB-MSC from five unrelated foals were compared using two-way MLR. For each of the five unrelated MSC cultures, paired MLR assays of MSC allowed five days of post-thaw culture and MSC included in MLR assay immediately post-thawing were evaluated. We report no difference in the suppression of lymphocyte proliferation by CB-MSC that had undergone post-thaw culture and MSC not cultured post-thaw (p<0.0001. Also, there was no inter-donor variability between the lymphocyte suppressive properties of MSC harvested from the five different donors (p = 0.13. These findings suggest that cryopreserved CB-MSC may have clinical utility immediately upon thawing. One implication hereof is the possibility of using cryopreserved CB-MSC at third party locations without the need for cell culture equipment or competencies.

  12. β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways.

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    Yunhui Du

    Full Text Available BACKGROUND: Autoantibodies against the second extracellular loop of the β(1-adrenergic receptor (β(1-AA not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β(1-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β(1-AA isolated from the sera of dilated cardiomyopathy (DCM patients caused the proliferation of T cells and the secretion of cytokines. METHODS: Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β(1-AA was detected using ELISA. The CD3(+T lymphocytes were selected separately through flow cytometry and the effect of β(1-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK. RESULTS: β(1-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β(1-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β(1-AA. β(1-AA also inhibited the secretion of interferon-γ (IFN-γ while promoting an increase in interleukin-4 (IL-4 levels. CONCLUSIONS: These results demonstrate that β(1-AA isolated from DCM patients binds to β(1-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1-AR/cAMP/PKA and p38 MAPK pathways.

  13. Protein kinase Cε regulates proliferation and cell sensitivity to TGF-1β of CD4+ T lymphocytes: implications for Hashimoto thyroiditis.

    Science.gov (United States)

    Mirandola, Prisco; Gobbi, Giuliana; Masselli, Elena; Micheloni, Cristina; Di Marcantonio, Daniela; Queirolo, Valeria; Chiodera, Paolo; Meschi, Tiziana; Vitale, Marco

    2011-11-01

    We have studied the functional role of protein kinase Cε (PKCε) in the control of human CD4(+) T cell proliferation and in their response to TGF-1β. We demonstrate that PKCε sustains CD4(+) T cell proliferation triggered in vitro by CD3 stimulation. Transient knockdown of PKCε expression decreases IL-2R chain transcription, and consequently cell surface expression levels of CD25. PKCε silencing in CD4 T cells potentiates the inhibitory effects of TGF-1β, whereas in contrast, the forced expression of PKCε virtually abrogates the inhibitory effects of TGF-1β. Being that PKCε is therefore implicated in the response of CD4 T cells to both CD3-mediated proliferative stimuli and TGF-1β antiproliferative signals, we studied it in Hashimoto thyroiditis (HT), a pathology characterized by abnormal lymphocyte proliferation and activation. When we analyzed CD4 T cells from HT patients, we found a significant increase of PKCε expression, accounting for their enhanced survival, proliferation, and decreased sensitivity to TGF-1β. The increased expression of PKCε in CD4(+) T cells of HT patients, which is described for the first time, to our knowledge, in this article, viewed in the perspective of the physiological role of PKCε in normal Th lymphocytes, adds knowledge to the molecular pathophysiology of HT and creates potentially new pharmacological targets for the therapy of this disease.

  14. Monocyte-derived dendritic cells enhance cell proliferation and porcine circovirus type 2 replication in concanavalin A-stimulated swine peripheral blood lymphocytes in vitro.

    Science.gov (United States)

    Lin, Chun-Ming; Jeng, Chian-Ren; Hsiao, Shih-Hsuan; Lee, Yao; Tsai, Yi-Chieh; Chia, Mi-Yuan; Pang, Victor Fei

    2012-01-15

    Dendritic cells (DCs) are professional antigen presenting cells cooperating with other immune cells for the activation of innate and adaptive immune responses. The objective of the present study was to investigate the replication activity of porcine circovirus type 2 (PCV2) in DCs and/or lymphocytes during their cross talk and its possible mechanism. Two models were set, herein. Swine blood monocyte (Mo)-derived DCs (MoDCs) or peripheral blood lymphocytes (PBLs) were inoculated with PCV2 prior to their co-cultivation. Bacterial lipopolysaccharide (LPS) and concanavalin A (Con A) were used to stimulate MoDCs and PBLs, respectively. During 6 days of cultivation, a high PCV2 antigen-containing rate without detectable intranuclear signals and a slight but significant increase in the copy number of PCV2 genome were detected in PCV2-inoculated MoDCs. The presence of LPS alone or PCV2-free PBLs, however, had no effect on the location of PCV2 antigens or copy number of PCV2 genome in PCV2-inoculated MoDCs. On the contrary, active PCV2 replication occurred in Con A-stimulated PCV2-inoculated PBLs. When compared with blood Mos, MoDCs induced significantly higher cell proliferation and intensified PCV2 replication in Con A-stimulated PCV2-inoculated PBLs, for which direct contact between MoDCs and lymphocytes was required. Among the cytokines secreted by Con A-activated PBLs, interleukin (IL)-2, but not IL-4 or interferon-γ, could induce cell proliferation and PCV2 replication in PCV2-inoculated PBLs. The findings suggest that although MoDCs support only limited PCV2 replication in themselves, their accessory cell function is required for cell proliferation and PCV2 replication in PCV2-infected lymphocytes.

  15. Immature dendritic cells generated from cryopreserved human monocytes show impaired ability to respond to LPS and to induce allogeneic lymphocyte proliferation.

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    Guilherme Ferreira Silveira

    Full Text Available Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs, the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

  16. Human Recombinant B7-H3 Expressed in E.coli Enhances T Lymphocyte Proliferation and IL-10 Secretion in Vitro

    Institute of Scientific and Technical Information of China (English)

    Guang-Bo ZHANG; Yong-Jing CHEN; Qin SHI; Hong-Bing MA; Yan GE; Qin WANG; Zhi JIANG; Ying XU; Xue-Guang ZHANG

    2004-01-01

    To explore the biofunctions of human B7-H3 on activated T lymphocyte,the gene of human B7-H3 encoding the extracellular region (IgV-like and IgC-like domains) was obtained by RT-PCR from human lung cells and subcloned into the prokaryotic expression vector pGEX-5X-3 to express glutathione S-transferase (GST) fusion protein.A 49 kD fusion protein (named as GST/hB7-H3 hereafter) was induced by IPTG and purified by standard methods reported in prokaryotic system.In the presence of the first signal imitated by anti-CD3 monoclonal antibody,T lymphocyte proliferation was observed by incubating purified T cells with soluble GST/hB7-H3 fusion protein by MTT assay.The concentrations of IFN-γ and IL-10 in the supernatants of T cells were determined by ELISA.The results showed that the GST/hB7-H3 protein produced in bacteria had modest biological activities to proliferate the T lymphocyte and enhance IFN-γ as well as IL-10 secretion.

  17. Using the geometric mean fluorescence intensity index method to measure ZAP-70 expression in patients with chronic lymphocytic leukemia

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    Wu YJ

    2016-02-01

    Full Text Available Yu-Jie Wu, Hui Wang, Jian-Hua Liang, Yi Miao, Lu Liu, Hai-Rong Qiu, Chun Qiao, Rong Wang, Jian-Yong Li Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China Abstract: Expression of ζ-chain-associated protein kinase 70 kDa (ZAP-70 in chronic lymphocytic leukemia (CLL is associated with more aggressive disease and can help differentiate CLL from cases expressing mutated or unmutated immunoglobulin heavy chain variable region (IgHV genes. However, standardizing ZAP-70 expression by flow cytometric analysis has proved unsatisfactory. The key point is that ZAP-70 is weakly expressed with a continuous expression pattern rather than a clear discrimination between positive and negative CLL cells, which means that the resulting judgment is subjective. Thus, in this study, we aimed at assessing the reliability and repeatability of ZAP-70 expression using the geometric mean fluorescence intensity (geo MFI index method based on flow cytometry with 256-channel resolution in a series of 402 CLL patients and to compare ZAP-70 with other biological and clinical prognosticators. According to IgHV mutational status, we were able to confirm that the optimal cut-off point for the geo MFI index was 3.5 in the test set. In multivariate analyses that included the major clinical and biological prognostic markers for CLL, the prognostic impact of ZAP-70 expression appeared to have stronger discriminatory power when the geo MFI index method was applied. In addition, we found that ZAP-70-positive patients according to the geo MFI index method had shorter time to first treatment or overall survival (P=0.0002, P=0.0491. This is the first report showing that ZAP-70 expression can be evaluated by a new approach, the geo MFI index, which could be a useful prognostic method as it is more reliable, less subjective, and therefore better associated with improvement of CLL prognostication

  18. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Catherine J., E-mail: cjwalsh@mote.org [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Butawan, Matthew, E-mail: mattbutawan@outlook.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Yordy, Jennifer, E-mail: jennifer.e.balmer@gmail.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Ball, Ray, E-mail: Ray.Ball@lowryparkzoo.com [Lowry Park Zoo, 1101 W Sligh Ave, Tampa, FL 33604 (United States); Flewelling, Leanne, E-mail: Leanne.Flewelling@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Wit, Martine de, E-mail: Martine.deWit@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Bonde, Robert K., E-mail: rbonde@usgs.gov [U.S. Geological Survey, Sirenia Project, 7920 NE 71st Street, Gainesville, FL 32653 (United States)

    2015-04-15

    Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

  19. Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

    Directory of Open Access Journals (Sweden)

    Sha-Sha Huang

    2016-10-01

    Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

  20. Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension.

    Science.gov (United States)

    Huang, Sha-Sha; Zhang, Qiu-Bing; Yuan, Qing-Yan; He, Si-Li; Zhang, Yuan-Ming

    2016-10-01

    Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4(+) T lymphocytes derived from Xinjiang Kazakh patients with hypertension. CD4(+) T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL)-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4(+) T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4(+) T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA) and protein expression of the Kv1.3 potassium channel in CD4(+) T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4(+) T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4(+) T lymphocytes. © The Author(s) 2016.

  1. Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation:A preliminary study

    Institute of Scientific and Technical Information of China (English)

    Md Moklesur Rahman Sarker; Long Chiau Ming; Md Zaidul Islam Sarker; M Shahabuddin Kabir Choudhuri

    2016-01-01

    Objective: To assess the immunopotentiality of Ayurvedic polyherbal preparations,“Saribadi”and“Anantamul Salsa”. Methods: Freshly prepared BALB/c mice splenocytes were cultured with“Saribadi”or“Anantamul Salsa” treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%, 3.00%and 4.00%(v/v)] at 37 ? C for 5 days. The immunoglobulin M (IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively. Endotoxin contamination was assessed by treating the preparations with polymyxin B. Results: The doses of“Saribadi”[0.25%, 0.50%, 0.75%and 1.00%(v/v)] significantly increased IgM productions (0.966, 0.728, 0.695 and 0.615 mg/mL vs. control 0.265 mg/mL) and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density (OD) vs. control 0.162 OD]. Similarly, the doses of“Anantamul Salsa”[0.50%, 0.75%, 1.00%and 1.50%(v/v)] promoted IgM productions (0.933, 0.919, 0.917 and 0.892 mg/mL vs. control 0.502 mg/mL) and the doses of “Anantamul Salsa” [0.50%, 0.75%, 1.00%, 1.50%, 2.00%, and 3.00%(v/v)] stimulated lymphocytes proliferation (absorbance 0.395, 0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of“Saribadi”and“Anantamul Salsa”was not retarded by the treatment of preparations with polymyxin B. Conclusions: Immunomodulatory activity of “Saribadi” and “Anantamul Salsa” was unveiled for the first time.“Saribadi”and“Anantamul Salsa”possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production. These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.

  2. Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation:A preliminary study

    Institute of Scientific and Technical Information of China (English)

    Md.Moklesur Rahman Sarker; Long Chiau Ming; Md.Zaidul Islam Sarker; M Shahabuddin Kabir Choudhuri

    2016-01-01

    Objective:To assess the immunopotentiality of Ayurvedic polyherbal preparations,"Saribadi" and "Anantamul Salsa".Methods: Freshly prepared BALB/c mice splenocytes were cultured with "Saribadi" or"Anantamul Salsa" treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%,3.00% and 4.00%(v/v)] at 37C for 5 days. The immunoglobulin M(IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively.Endotoxin contamination was assessed by treating the preparations with polymyxin B.Results: The doses of "Saribadi" [0.25%, 0.50%, 0.75% and 1.00%(v/v)] significantly increased IgM productions(0.966, 0.728, 0.695 and 0.615 mg/m L vs. control 0.265 mg/m L)and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density(OD) vs. control 0.162 OD]. Similarly, the doses of "Anantamul Salsa" [0.50%, 0.75%,1.00% and 1.50%(v/v)] promoted IgM productions(0.933, 0.919, 0.917 and 0.892 mg/m L vs. control 0.502 mg/m L) and the doses of "Anantamul Salsa" [0.50%, 0.75%, 1.00%,1.50%, 2.00%, and 3.00%(v/v)] stimulated lymphocytes proliferation(absorbance 0.395,0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of "Saribadi"and "Anantamul Salsa" was not retarded by the treatment of preparations with polymyxin B.Conclusions: Immunomodulatory activity of "Saribadi" and "Anantamul Salsa" was unveiled for the first time. "Saribadi" and "Anantamul Salsa" possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production.These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.

  3. Standardisation and quality assurance of lymphocyte proliferation assays for use in the assessment of immune function. European Concerted Action on Immunological and Virological Markers of HIV Disease Progression.

    Science.gov (United States)

    Froebel, K S; Pakker, N G; Aiuti, F; Bofill, M; Choremi-Papadopoulou, H; Economidou, J; Rabian, C; Roos, M T; Ryder, L P; Miedema, F; Raab, G M

    1999-07-30

    Lymphocyte proliferation is a widely used technique to assess immune competence. However, the technique is subject to a large degree of variation, some biological and some technical. In this study, the components of variation in whole blood proliferation assays were analysed over time, using both antibody and mitogenic stimulants. The levels of variation within individual samples, between individuals and between groups of individuals over time were examined. A method of transforming the data is proposed which reduces the coefficients of variation to an acceptable level, and which expresses individual results as a standardised count. This method overcomes the problem of different levels of absolute counts, it corrects for time sensitive errors and allows data from multiple laboratories to be pooled.

  4. The 15N and 46R Residues of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Enhance Regulatory T Lymphocytes Proliferation.

    Directory of Open Access Journals (Sweden)

    Baochao Fan

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV negatively modulates host immune responses, resulting in persistent infection and immunosuppression. PRRSV infection increases the number of PRRSV-specific regulatory T lymphocytes (Tregs in infected pigs. However, the target antigens for Tregs proliferation in PRRSV infection have not been fully understood. In this study, we demonstrated that the highly pathogenic PRRSV (HP-PRRSV induced more CD4+CD25+Foxp3+ Tregs than classical PRRSV (C-PRRSV strain. Of the recombinant GP5, M and N proteins of HP-PRRSV expressed in baculovirus expression systems, only N protein induced Tregs proliferation. The Tregs assays showed that three amino-acid regions, 15-21, 42-48 and 88-94, in N protein played an important role in induction of Tregs proliferation with synthetic peptides covering the whole length of N protein. By using reverse genetic methods, it was firstly found that the 15N and 46R residues in PRRSV N protein were critical for induction of Tregs proliferation. The phenotype of induced Tregs closely resembled that of transforming-growth-factor-β-secreting T helper 3 Tregs in swine. These data should be useful for understanding the mechanism of immunity to PRRSV and development of infection control strategies in the future.

  5. The 15N and 46R Residues of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Enhance Regulatory T Lymphocytes Proliferation.

    Science.gov (United States)

    Fan, Baochao; Liu, Xing; Bai, Juan; Li, Yufeng; Zhang, Qiaoya; Jiang, Ping

    2015-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) negatively modulates host immune responses, resulting in persistent infection and immunosuppression. PRRSV infection increases the number of PRRSV-specific regulatory T lymphocytes (Tregs) in infected pigs. However, the target antigens for Tregs proliferation in PRRSV infection have not been fully understood. In this study, we demonstrated that the highly pathogenic PRRSV (HP-PRRSV) induced more CD4+CD25+Foxp3+ Tregs than classical PRRSV (C-PRRSV) strain. Of the recombinant GP5, M and N proteins of HP-PRRSV expressed in baculovirus expression systems, only N protein induced Tregs proliferation. The Tregs assays showed that three amino-acid regions, 15-21, 42-48 and 88-94, in N protein played an important role in induction of Tregs proliferation with synthetic peptides covering the whole length of N protein. By using reverse genetic methods, it was firstly found that the 15N and 46R residues in PRRSV N protein were critical for induction of Tregs proliferation. The phenotype of induced Tregs closely resembled that of transforming-growth-factor-β-secreting T helper 3 Tregs in swine. These data should be useful for understanding the mechanism of immunity to PRRSV and development of infection control strategies in the future.

  6. Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1.

    Science.gov (United States)

    Jia, Wei; He, Ming-Xiao; McLeod, Ian X; Guo, Jian; Ji, Dong; He, You-Wen

    2015-01-01

    The highly conserved cellular degradation pathway, macroautophagy, regulates the homeostasis of organelles and promotes the survival of T lymphocytes. Previous results indicate that Atg3-, Atg5-, or Pik3c3/Vps34-deficient T cells cannot proliferate efficiently. Here we demonstrate that the proliferation of Atg7-deficient T cells is defective. By using an adoptive transfer and Listeria monocytogenes (LM) mouse infection model, we found that the primary immune response against LM is intrinsically impaired in autophagy-deficient CD8(+) T cells because the cell population cannot expand after infection. Autophagy-deficient T cells fail to enter into S-phase after TCR stimulation. The major negative regulator of the cell cycle in T lymphocytes, CDKN1B, is accumulated in autophagy-deficient naïve T cells and CDKN1B cannot be degraded after TCR stimulation. Furthermore, our results indicate that genetic deletion of one allele of CDKN1B in autophagy-deficient T cells restores proliferative capability and the cells can enter into S-phase after TCR stimulation. Finally, we found that natural CDKN1B forms polymers and is physiologically associated with the autophagy receptor protein SQSTM1/p62 (sequestosome 1). Collectively, autophagy is required for maintaining the expression level of CDKN1B in naïve T cells and selectively degrades CDKN1B after TCR stimulation.

  7. Grading ductal carcinoma in situ of the breast using an automated proliferation index.

    Science.gov (United States)

    Stasik, Christopher J; Davis, Marilyn; Kimler, Bruce F; Fan, Fang; Damjanov, Ivan; Thomas, Patricia; Tawfik, Ossama W

    2011-01-01

    Tumor grade, size and margin status are the most significant factors in predicting the behavior of ductal carcinoma in-situ (DCIS). The inclusion of necrosis and nuclear grade in the grading of DCIS has demonstrated a fair but suboptimal agreement between pathologists. The grading of DCIS was studied and compared to the Van Nuys (VN) system, by using our newly proposed unifying "nuclear grade + proliferation index (N+P) grading system for invasive carcinomas. 162 DCIS tumors were studied including 49 VN I, 31 VN II, and 82 VN III cases. The VN and N+P systems were compared with each other and correlated with tumor size, ER, PR, p53, Her-2, EGFR, Bcl-2, p27 and p21 status. The two systems demonstrated similar frequencies for the different grades and an agreement with each other for all of the biomarkers studied. The greatest difference between the two systems was observed for those tumors initially classified as VN II (94% being down-graded to N+P I) and VN III (80% being down-graded to N+P II). These results suggest that the N+P system, combining nuclear grade with automated MIB-1 count, is a potentially valid and reproducible grading system for both non-invasive and invasive mammary carcinomas. It is automated, less subjective in assessing mitotic activity and necrosis and correlates with other prognostic biomarkers.

  8. Long-term cadmium exposure leads to the enhancement of lymphocyte proliferation via down-regulating p16 by DNA hypermethylation.

    Science.gov (United States)

    Yuan, Dexiao; Ye, Shuang; Pan, Yan; Bao, Yizhong; Chen, Honghong; Shao, Chunlin

    2013-10-09

    Cadmium (Cd) is a well-established carcinogen, however, the underlying mechanism, especially the role of epigenetics in it, is still poorly understood. Our previous work has disclosed that when rats were exposed to 0.5mg CdCl2 (kgd) for 8 and 12 weeks, the growth of peripheral white blood cells (WBC) was obviously stimulated but no over-proliferation of granulocyte-monocyte (GM) progenitor cells was observed in the bone marrow, suggesting that the over-proliferation of lymphocyte was promoted by Cd exposure. Is DNA-methylation involved in this Cd-stimulated cell proliferation? The present study found that when human B lymphoblast HMy2.CIR cells were exposed to Cd with a dose lower than 0.1μM for 3 months, both cell proliferation and mRNA expressions of DNA methyltransferases of DNMT1 and DNMT3b were increased, while the mRNA of tumor suppressor gene p16 was remarkably decreased. Furthermore, the level of genomic DNA methylation was increased and the CpG island in p16 promoter was hypermethylated in the Cd-exposed cells. A DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), diminished Cd-stimulated cell proliferation associated with p16 overexpression. Our results suggested that the chronic exposure of low dose Cd could induce hypermethylation of p16 promoter and hence suppress p16 expression and then promote cell proliferation, which might contribute to Cd-induced carcinogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Li, Heng; Yi, Shu-Hua; Xiong, Wen-Jie; Liu, Hui-Min; Lyu, Rui; Wang, Ting-Yu; Liu, Wei; Zhong, Shi-Zhen; Yu, Zhen; Zou, De-Hui; Xu, Yan; An, Gang; Li, Zeng-Jun; Qiu, Lu-Gui

    2017-01-01

    Background: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI). Methods: Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT. Results: The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3–6]) with significantly different TTFT

  10. Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index

    Directory of Open Access Journals (Sweden)

    Solberg Peter

    2007-01-01

    Full Text Available Abstract Background CD4+ T lymphocyte (CD4 cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART, but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb, and body mass index (BMI to identify patients who require ART. Methods We conducted a cross-sectional study of HIV-infected adults in Uganda, who presented for assessment for ART-eligibility with WHO clinical stages I, II or III. Two by two tables were constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell counts ≤ 200 cells μL, while minimizing the number offered ART with counts > 350 cells μL. Hb and BMI values were then examined to try to improve model performance. Results 1787 subjects were available for analysis. Median CD4 cell counts and TLCs, were 239 cells/μL and 1830 cells/μL, respectively. Offering ART to all subjects with a TLCs ≤ 2250 cells/μL produced a sensitivity of 0.88 and a false positive ratio of 0.21. Algorithms that treated all patients with a TLC 3000 cells/μL, and used Hb and/or BMI values to determine eligibility for those with TLC values between 2000 and 3000 cells/μL, marginally improved accuracy. Conclusion TLCs appear useful in predicting who would be eligible for ART based on CD4 cell count criteria. Hb and BMI values may be useful in prioritizing patients for ART, but did not improve model accuracy.

  11. Application of lymphocyte parameters in screening lymphocyte proliferation and reactive hyperplasia disease%淋巴细胞参数在筛选淋巴细胞增殖及反应性增生疾病中的应用

    Institute of Scientific and Technical Information of China (English)

    徐卫益; 胡海莹; 汤冬琴

    2014-01-01

    Objective To investigate the application of lymphocyte parameters in screening the lymphocyte proliferation and re-active hyperplasia disease.Methods 128 cases as the healthy control,100 cases of lymphoma,35 cases of multiple myeloma(MM), 34 cases of lymphocytes reactive hyperplasia(RL)and 5 cases of chronic lymphocytic leukemia(CLL)were selected and performed the peripheral blood cells analysis by the Sysmex XE-2100 hematology analyzer.The relevant lymphocyte parameter values were re-corded and the comparative analysis in the difference between the disease groups and the control group was performed.The role of each lymphocyte parameter in screening the lymphocyte proliferation and reactive hyperplasia diseases was evaluated by the receiver operating characteristic curve(ROC curve).Results The high fluorescence lymphocytes(HFL),in the control group was 0.008 ± 0.008,in the lymphoma group was 0.016±0.058,in the MM group was 0.019 ±0.063,in the RL group was 0.040 ±0.070,and CLL group was 0.388±0.158.Compared with control group,the difference of RL and CLL group was statistically significant(P morphological changes of lymphocytes sensitively and contribute to screening the patients with lymphocyte proliferation and reactive hyperplasia disease.%目的:探讨淋巴细胞参数在淋巴细胞增殖及反应性增生疾病筛查中的应用。方法选取健康对照组128例、淋巴瘤患者100例、多发性骨髓瘤(MM)患者35例、淋巴细胞反应性增生(RL)患者34例、慢性淋巴细胞白血病(CLL)患者5例。分别用 Sysmex XE-2100血液分析仪进行外周血血细胞分析,记录相应淋巴细胞参数值,并对其进行疾病组与对照组差异比较分析;以受试者操作特性曲线(ROC 曲线)评价各淋巴细胞参数在筛选淋巴细胞增殖及反应性增生疾病患者中的作用。结果高荧光淋巴细胞(HFL):对照组0.008±0.008,淋巴瘤组0.016±0.058,MM 组0.019±0.063,RL 组0.040±0

  12. Quantitative miR analysis in chronic lymphocytic leukaemia/small lymphocytic lymphoma - proliferation centres are characterized by high miR-92a and miR-155 and low miR-150 expression.

    Science.gov (United States)

    Szurián, Kinga; Csala, Irén; Piurkó, Violetta; Deák, Linda; Matolcsy, András; Reiniger, Lilla

    2017-07-01

    Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal abnormalities have already been described to accumulate preferably in the PCs as opposed to the intervening small cell areas. To further characterize the pathogenic role of PCs, the expression levels of 17 selected miRs known to be involved in the development of CLL/SLL were compared in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL. The miR expression levels were also compared to the cytogenetic alterations defined by FISH analysis. Our results show that two known oncomiRs, miR-155 and -92a were upregulated and the tumour suppressor miR-150 was downregulated in the PCs. Low expression of miR-150 was also associated with loss of 11q. In summary we found significantly higher expression of oncomiRs and lower expression of a tumour suppressor miR in PCs of CLL/SLL lymph nodes, which support the hypothesis that the PCs may drive the disease and play a role in progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Murine Butyrophilin-like (Btnl 1 and Btnl6 form heteromeric complexes in small intestinal epithelial cells and promote proliferation of local T lymphocytes

    Directory of Open Access Journals (Sweden)

    Cristina eLebrero-Fernández

    2016-01-01

    Full Text Available To date, few molecular conduits mediating the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes (IELs have been described. We recently showed that Butyrophilin-like (Btnl 1 can attenuate the epithelial response to activated IELs, resulting in reduced production of pro-inflammatory mediators such as IL-6 and CXCL1. We here report that like Btnl1, murine Btnl6 expression is primarily confined to the intestinal epithelium. Although Btnl1 can exist in a cell surface-expressed homomeric form, we found that it additionally forms heteromeric complexes with Btnl6, and that the engagement of Btnl1 is a prerequisite for surface expression of Btnl6 on intestinal epithelial cells. In an IEL-epithelial cell co-culture system, enforced epithelial cell expression of Btnl1 significantly enhanced the proliferation of IELs in the absence of exogenous activation. The effect on proliferation was dependent on the presence of IL-2 or IL-15 and restricted to IELs upregulating CD25. In the gamma delta (gd T-cell subset, the Btnl1-Btnl6 complex, but not Btnl1, specifically elevated the proliferation of IELs bearing the Vg7Vd4 receptor. Thus, our results show that murine epithelial cell-specific Btnl proteins can form intrafamily heterocomplexes, and suggest that the interaction between Btnl proteins and IELs regulates the expansion of IELs in the intestinal mucosa.

  14. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation.

    Science.gov (United States)

    Shibuya, Kazuko; Shirakawa, Jun; Kameyama, Tomie; Honda, Shin-Ichiro; Tahara-Hanaoka, Satoko; Miyamoto, Akitomo; Onodera, Masafumi; Sumida, Takayuki; Nakauchi, Hiromitsu; Miyoshi, Hiroyuki; Shibuya, Akira

    2003-12-15

    Upon antigen recognition by the T cell receptor, lymphocyte function-associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12-independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1-mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.

  15. Dose-dependent in vivo effect of Rhodiola and Echinacea on the mitogen-induced lymphocyte proliferation in mice.

    Science.gov (United States)

    Skopińska-Rózewska, E; Sokolnicka, I; Siwicki, A K; Stankiewicz, W; Dabrowski, M P; Buchwald, W; Krajewska-Patan, A; Mielcarek, S; Mścisz, A; Furmanowa, M

    2011-01-01

    Echinacea purpurea (EP) and Echinacea angustifolia (EA) are ones of the most important world's herbs with immunotropic activity. They were traditional medicinal plants used by North American Indians for the treatment of various illnesses. Now they are cultivated in many countries and are used mainly to treat respiratory tract infections. Rhodiola rosea (RR) and Rhodiola quadrifida (RQ) are medicinal plants originated from Asia and used traditionally as adaptogens, antidepressants, and anti-inflammatory remedies. We previously reported, that extracts of underground parts of RR and RQ exhibited immunotropic activity. We have demonstrated in pigs that in vitro RR or RQ supplementation of blood lymphocyte cultures stimulated T cell proliferative response to Con A in lower, and inhibited it in higher Rhodiola extract concentrations. The aim of this work was to evaluate the in vivo effect of these herbal remedies on the in vitro proliferative response of mouse splenic lymphocytes to another T-cell mitogen- Phaseolus vulgaris haemagglutinin (PHA). We have found significant stimulation of proliferative response, in comparison to the controls, in mice fed lower doses of tested remedies, and inhibition, no effect or lower stimulation, in mice fed higher doses of these drugs.

  16. Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    IL-4 is an important B cell survival and growth factor.IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts.Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase in both resting and activated cells.By contrast,association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed.However,IL-4 induced association of IRS2 with GRB2 in B cell blasts.The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice.While IL-4 alone does not induce activation of MEK,a MEK1 inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts.These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation.Furthermore,proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

  17. The improvement effects of edible bird’s nest on proliferation and activation of B lymphocyte and its antagonistic effects on immunosuppression induced by cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Zhao R

    2016-01-01

    Full Text Available Ran Zhao,1,* Geng Li,1,* Xiu-juan Kong,1 Xiu-yan Huang,2 Wei Li,1 Yao-ying Zeng,2 Xiao-ping Lai31Traditional Chinese Medicinal College, Guangzhou University of Chinese Medicine, 2Life Science College, Jinan University, Guangzhou, 3Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, People’s Republic of China*These authors contributed equally to this workAbstract: Edible bird’s nest (EBN is regarded as an immune-enhancing food in the People’s Republic of China. The aim of this study is to demonstrate the efficiency of EBN in improving the immunity of mouse both in vivo and in vitro. We observed the effects of EBN on spleen lymphocytes proliferation and activation, as well as immunoglobulin isotypes as indicators. In addition, we evaluated the content of total sIgA in the intestinal juice to assess mucosal immunity. The results showed that EBN could promote the proliferation and activation of B-cells and increase IgE, IgA, IgM, and IgG3 levels. We also found that EBN extract can promote the secretion of sIgA in the small intestine. Using cyclophosphamide (CY, we established an immunosuppressed mouse model in which we identified a reversal influence on the ratio of CD3+/CD19+ cells, which indicates that EBN also protects B-cells from the damage induced by CY. We also applied polymyxin B to exclude the interference of lipopolysaccharide throughout the experiment. In conclusion, we found that EBN can reduce the intestinal immune injury induced by CY by accelerating the proliferation and activation of B-cells and enhancing antibody secretion of B-cells.Keywords: chemotherapy, immunological enhancement, intestinal mucosal immune, EBN

  18. Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals

    DEFF Research Database (Denmark)

    Theander, T G; Bygbjerg, I C; Jepsen, S

    1986-01-01

    -immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg...... and that this activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when...

  19. 氧化苦参碱对小鼠淋巴结T细胞增殖的双向作用%Two-ways effects of Oxymatrine on T lymphocyte proliferation in mouse lymph node stimulated by Con A

    Institute of Scientific and Technical Information of China (English)

    伍斌; 谢红付; 李罗丝; 张江林; 李建国

    2006-01-01

    [Objective] To investigate the effects of Oxymatrine (OMT) on mouse lymphocyte proliferation stimulated by Con A, explore the mechanism of the effects of OMT on the immune system and provide theoretical and experimental evidence for the clinical application of OMT in treating immune-related diseases. [Methods] CFDA-SE staining and flow cytometry were used to detect the fluorescence intensity of lymphocytes after stimulated by polyclonal stimulators Con A and OMT. Related softwares were used to analyze the effects of OMT on mouse lymphocyte proliferation. [Results] OMT has the function to restrain the proliferation of lymphocyte of mouse depended on its concentration with 500, 125 and 31 μg/mL in substrate, but 16, 8, 4, 2 μg/mL concentration, it improves the proliferation of T lymphocytes of mouse's lymph node, the dependence on its concentration is not significant. [Conclusions ] 1. Both CFDA-SE dyeing and flow cytometer were reliable tools to analyze lymphocyte proliferation. 2. OMT has the two-ways effects on T lymphocyte proliferation in mouse lymph node stimulated by Con A.%目的检测氧化苦参碱(Oxymatrine,OMT)对刀豆蛋白A(Con A)刺激的小鼠淋巴结T细胞增殖的影响,探讨OMT对免疫系统的作用机制,为临床用OMT治疗免疫相关性疾病提供理论和实验依据.方法利用CFDA-SE染色,流式细胞术检测淋巴细胞在多克隆刺激剂Con A和OMT的共同作同下荧光强度的变化,并应用CELLQuest软件分析OMT对小鼠淋巴结T细胞增殖的影响程度.结果 500、125和31μg/mLOMT对小鼠淋巴结T细胞增殖呈剂量依赖性抑制,而16、8、4、2μg/mL OMT对小鼠淋巴结T细胞增殖起促进作用,但其剂量依赖关系不明显.结论 CFDA-SE染色和流式细胞术是分析淋巴细胞增殖的有力工具:OMT对小鼠淋巴结T细胞的增殖呈双向作用.

  20. Ki-67 proliferation index but not mitotic thresholds integrates the molecular prognostic stratification of lower grade gliomas

    Science.gov (United States)

    Duregon, Eleonora; Bertero, Luca; Pittaro, Alessandra; Soffietti, Riccardo; Rudà, Roberta; Trevisan, Morena; Papotti, Mauro; Ventura, Laura; Senetta, Rebecca; Cassoni, Paola

    2016-01-01

    Despite several molecular signatures for “lower grade diffuse gliomas” (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor “proliferative trait” (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG. PMID:27049832

  1. The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome.

    Directory of Open Access Journals (Sweden)

    Sergio Matarraz

    Full Text Available Myelodysplastic syndromes (MDS are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94 and acute myeloid leukemia (AML; n = 30 cases using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+ precursors, maturing neutrophils and nucleated red blood cells (NRBC, while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+ HPC, could significantly contribute to a better management of MDS.

  2. The Proliferation Index of Specific Bone Marrow Cell Compartments from Myelodysplastic Syndromes Is Associated with the Diagnostic and Patient Outcome

    Science.gov (United States)

    Matarraz, Sergio; Teodosio, Cristina; Fernandez, Carlos; Albors, Manuel; Jara-Acevedo, María; López, Antonio; Gonzalez-Gonzalez, María; Gutierrez, María Laura; Flores-Montero, Juan; Cerveró, Carlos; Pizarro-Perea, Marlies; Garrastazul, María Paz; Caballero, Gonzalo; Gutierrez, Oliver; Mendez, Guy Daniel; González-Silva, Manuel; Laranjeira, Paula; Orfao, Alberto

    2012-01-01

    Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM) associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI) of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34+ precursors, maturing neutrophils and nucleated red blood cells (NRBC), while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS) and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34+ HPC), could significantly contribute to a better management of MDS. PMID:22952954

  3. Computerized image analysis of the Ki-67 proliferation index in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Blaker, Yngvild N; Brodtkorb, Marianne; Maddison, John;

    2015-01-01

    practice. The aim of this study was to investigate the use of computerized image analysis software for scoring of Ki-67 in MCL. METHODS AND RESULTS: We developed an automated method for determining the Ki-67 index by computerized image analysis and tested it using a cohort of 62 MCL patients. The data were...... compared to Ki-67 scores obtained by semiquantitative estimation and image-based manual counting. When using the Ki-67 index as a continuous parameter, both image-based manual counting and computerized image analysis were related inversely to survival (P = 0.020 and P = 0.025, respectively). Ki-67 index...... obtained by semiquantitative estimation was not associated significantly with survival (P = 0.093). The results were validated in a second patient cohort with similar results. CONCLUSION: Computerized image analysis of the Ki-67 index in MCL is an attractive alternative to semiquantitative estimation...

  4. Effects of Neuromedin S on the Proliferation of Splenic Lymphocytes and the Cytokine Secretion by Pulmonary Alveolar Macrophages in Pigs in vitro.

    Science.gov (United States)

    Lin, R; Wang, Q; Qi, B; Huang, Y; Yang, G

    2016-09-01

    Neuromedin S (NMS), a 36-amino acid neuropeptide, has been found to be involved in the regulation of the endocrine activity. It has been also detected in immune tissues in mammals, what suggests that NMS may play an important role in the regulation of immune response. The aim of this study was to demonstrate the presence of NMS receptor 1 (NMU1R) and effect of NMS in pig splenic lymphocytes (SPLs) and pulmonary alveolar macrophages (PAMs). The presence of NMU1R in pig SPLs and PAMs was respectively confirmed by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunocytochemical methods. Furthermore, SPL proliferation was analyzed using the 3-(4,5)-dimethyl-thiahiazo-(-2-yl)-3,5-di-phenytetrazoliumromide (MTT) method. Additionally, the secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in PAMs was all measured by enzyme-linked immunosorbent assay (ELISA) kits. In the present study, the results of RT-PCR and western blot analysis revealed that NMU1R mRNA and protein were both expressed in pig SPLs and PAMs, and the immunocytochemical investigations further revealed that the positive signal of NMU1R immunoreactivity was observed in plasma membranes of both SPLs and PAMs. In the in vitro study, we found that at concentrations of 0.001-1000 nM NMS alone or combined with lipopolysaccharide or phytohemagglutinin significantly increased SPL proliferation. Application of ELISA method showed that NMS could induce the secretion of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in PAMs. These results suggest that NMS can act as a potently positive pro-inflammatory factor and immunomodulatory agent that affects the immune response of immune cells by combining with its receptor NMU1R.

  5. Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and prognostic nutrition index as preoperative predictors of early mortality after liver resection for huge (≥10 cm) hepatocellular carcinoma.

    Science.gov (United States)

    Goh, Brian K P; Kam, Juinn Huar; Lee, Ser-Yee; Chan, Chung-Yip; Allen, John C; Jeyaraj, Premaraj; Cheow, Peng-Chung; Chow, Pierce K H; Ooi, London L P J; Chung, Alexander Y F

    2016-05-01

    This study aimed to determine preoperative predictors of early (huge (≥10 cm) HCC, with special emphasis on the importance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI). Between 2000 to 2013, 166 patients underwent LR for huge HCC. Optimal cut-offs for alpha fetoprotein (AFP), NLR, PLR, and PNI were determined by plotting the receiver operator curves (ROC) in predicting early mortality and utilizing the Youden index. The 30-day/in-hospital postoperative mortality rate was 4.2%. The 5-year overall survival (OS) and the 5-year recurrence-free survival (RFS) was 43% and 24%, respectively. Early mortality from disease recurrence occurred in 35 of 159 (22%) patients. Multivariate analyses demonstrated that tumor rupture and high AFP (>1,085 ng/ml) were independent preoperative predictors of early mortality after LR for HCC, and both a low PNI (huge HCC. J. Surg. Oncol. 2016;113:621-627. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Sister chromatid exchange in human lymphocytes induced by propoxur following plant activation by Vicia faba.

    Science.gov (United States)

    Gómez-Arroyo, S; Calderón-Segura, M E; Villalobos-Pietrini, R

    1995-01-01

    Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration-response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2,000 ppm). This general behavior was in agreement with the presence of an enzymatic system (S10 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2,000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected.

  7. Mitogen-induced lymphocyte proliferation in loggerhead sea turtles: comparison of methods and effects of gender, plasma testosterone concentration, and body condition on immunity.

    Science.gov (United States)

    Keller, Jennifer M; McClellan-Green, Patricia D; Lee, A Michelle; Arendt, Mike D; Maier, Philip P; Segars, Al L; Whitaker, J David; Keil, Deborah E; Peden-Adams, Margie M

    2005-02-10

    A fully functioning immune system is vital to the survival of threatened and endangered sea turtles. Immunological protection against diseases in any organism can be reduced by a number of natural and anthropogenic factors, such as seasonal changes, malnutrition, disease states, and contaminant exposure. These factors are even more critical when they occur in endangered species or populations. To identify alterations in the immunological health of loggerhead sea turtles (Caretta caretta), the mitogen-induced lymphocyte proliferation (LP) assay was developed using peripheral blood leukocytes (PBLs). Collection and culture conditions were optimized for this assay using non-lethal blood samples collected from free-ranging turtles along the southeastern US coast. During the collection, two anticoagulants (sodium heparin and lithium heparin) were compared to determine effects of different ions on assay results. Optimal culture conditions were established for loggerhead PBLs while two different methods of measuring LP were compared: (1) the traditional radioactive (3)H-thymidine assay and (2) a non-radioactive, colorimetric method utilizing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium (MTT). The results indicate that the (3)H-thymidine and the non-radioactive MTT methods did not correlate with each other and that the use of heparin type did not influence the results of the LP assay. Lastly, using these optimized methods, we investigated the effect of gender, plasma testosterone concentration, and body condition on LP in loggerhead turtles and found that none of the parameters largely influenced LP.

  8. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  9. “Double hit” follicular lymphoma with low proliferation index: A unique case and literature review

    Directory of Open Access Journals (Sweden)

    Pardis Vafaii

    2017-03-01

    Full Text Available “Double hit” lymphomas (DHLs are aggressive B-cell lymphomas with concurrent c-MYC and BCL2 and/or BCL6 gene rearrangements. DHLs are usually classified morphologically as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL and Burkitt lymphoma, and less commonly as DLBCL. Follicular lymphoma (FL is characterized genetically by the presence of IGH-BCL2 rearrangement. A subset of DHLs arises from FL by the acquisition of c-MYC gene rearrangement during disease progression, but FL with concurrent IGH-BCL2 and c-MYC gene initial rearrangements is rarely reported. The few reported cases had different clinical courses, including some with indolent disease. We report a case of “double hit” low grade FL with both c-MYC and BCL2 gene rearrangements but at low proliferation rate. Unlike the usual DHLs with aggressive clinical course, our patient showed at least partial response to intense chemotherapy. Review of the literature shows a few similar cases with variable clinical course, including a few indolent cases. These patients appear to respond better with more intense chemotherapy for DHL.

  10. The Association of Geriatric Nutritional Risk Index and Total Lymphocytes Count with Mortality in Korean Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Kiryong Park, M.D.

    2012-06-01

    Conclusion: These results demonstrate that the GNRI may be a significant predictor of mortality in Korean hemodialysis patients. However, the use of TLC might improve the evaluation of nutritional risk and the identification of patients at risk of malnutrition.Figure 1. Total lymphocytes count and 120-month survival of hemodialysis patients. In both groups, survival rate during the follow-up period was similar. (life table analysis, P = 0.500.fx1

  11. Cell Proliferation Activity and Prognostic Index in Squamous Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    José Antonio Alvarez-Riesgo

    1998-01-01

    Full Text Available Flow Cytometry (FC has been incorporated into cancer research in relation to its prognostic value together with histological parameters and TNM stages. We have studied by means of FC the cell cycle of 132 samples from male patients with Squamous Cell Lung Carcinoma (SQCLC. All of the patients received curative surgery and the clinical follow-up was 60 months. The clinical and cytometric parameters were evaluated in order to predict the patients’ outcome. The presence of tumoural recurrence and the tumoural stage showed statistical significance associated with survival. The multivariant analysis reveals radiotherapy (p = 0.004 as protective variable and the high S-phase fraction (SPF (p = 0.001 and stage IIIA (p = 0.012 as risk factors. The SPF appears as an independent prognostic factor for overall survival time. We can build a prognostic index representative of different prognostic groups, which allows us to improve the individual monitoring of these patients.

  12. Cell Proliferation Activity and Prognostic Index in Squamous Cell Lung Carcinoma

    Science.gov (United States)

    Alvarez-Riesgo, José Antonio; Sampedro, Andrés; Hernández, Radhamés; Folgueras, María Victoria; Salas-Bustamante, Ana; Cueto, Antonio

    1998-01-01

    Flow Cytometry (FC) has been incorporated into cancer research in relation to its prognostic value together with histological parameters and TNM stages. We have studied by means of FC the cell cycle of 132 samples from male patients with Squamous Cell Lung Carcinoma (SQCLC). All of the patients received curative surgery and the clinical follow-up was 60 months. The clinical and cytometric parameters were evaluated in order to predict the patients’ outcome. The presence of tumoural recurrence and the tumoural stage showed statistical significance associated with survival. The multivariant analysis reveals radiotherapy (p = 0.004) as protective variable and the high S-phase fraction (SPF) (p = 0.001) and stage IIIA (p = 0.012) as risk factors. The SPF appears as an independent prognostic factor for overall survival time. We can build a prognostic index representative of different prognostic groups, which allows us to improve the individual monitoring of these patients. PMID:9762370

  13. Plasmid DNA as a special stimular to stimulate lymphocyte proliferation%DNA作为一种特异性刺激剂刺激淋巴细胞增殖的研究

    Institute of Scientific and Technical Information of China (English)

    吴琼; 孙英军; 张艳; 郑海学

    2011-01-01

    目的 为了探讨质粒DNA体外刺激淋巴细胞的增殖状况,建立了一种方便可靠的评价豚鼠细胞免疫水平的试验方法.方法 用羧基荧光素乙酰乙酸琥珀酰亚胺酯(cFsEl染色豚鼠全血,经植物血凝素(PHA)和质粒DNA刺激培养,利用流式细胞术分析细胞的增殖状况.结果 豚鼠全血经PHA和DNA刺激,淋巴细胞增殖能力不同;未免疫组经DNA和PHA刺激后增殖的差异显著,免疫组差异不显著.DNA质粒在体内外均可作为刺激源刺激淋巴细胞增殖.结论 建立了一种基于活细胞染料CFSE染色的豚鼠全血淋巴细胞增殖试验方法,可方便、快速、有效地评价细胞免疫水平.%To investigate the level of lymphocyte proliferation stimulated by plasmid DNA in vitro, and to establish a convenient and reliable method to assess the level of cellular immunity in guinea pig, the whole blood of guinea pig was stained by Carboxyfluorescein diacetate succinimidyl ester (CFSE), then stimulated by phytohemagglutinin(PHA) and plasmid DNA, and cultivated for 3 days.The cell proliferation was detected by flow cytometry.We observed that PHA and DNA stimulation could promote lymphocyte proliferation: the proliferation in non-immune group was significantly enhanced, while the inactivated vaccine immune group did not significantly changed, which indicate that plasmid DNA can be used as animmunogen to stimulate lymphocyte proliferation.Through this study, a live cell-based dye CFSE staining of guinea pig whole blood lymphocyte proliferation test method was established to evaluate the cellular immunity conveniently and effectively.

  14. Stimulation of AIDS lymphocytes with calcium ionophore (A23187) and phorbol ester (PMA): studies of cytoplasmic free Ca, IL-2 receptor expression, IL-2 production, and proliferation

    DEFF Research Database (Denmark)

    Hofmann, B; Moller, J; Langhoff, E

    1989-01-01

    nine patients with AIDS with the response of lymphocytes from nine control subjects showed that the response of AIDS lymphocytes was severely decreased when stimulated with PHA and no further response could be achieved by stimulation with A23187/PMA. On the other hand, no significant difference between...... the PHA-induced rise of cytoplasmic free calcium concentration ([Ca2+]1) in normal and AIDS lymphocytes was observed. The percentage of cells expressing IL-2 receptors (CD25) was also normal both after addition of PHA and after addition of A23187/PMA and the expression was normal on both CD4 and CD8 cells....... The production of IL-2 in normal lymphocytes stimulated with A23187/PMA was 33 times higher than that after stimulation with PHA. In AIDS lymphocytes the production of IL-2 induced by all activators was severely decreased compared to control subjects, although the production of IL-2 after stimulation with A23187...

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

    Science.gov (United States)

    Maj, Tomasz; Slawek, Anna

    2014-01-01

    Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs) derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA) were cocultured with CD4+ T cells derived from OT-II mice's (C57BL6/J-Tg(TcraTcrb)1100Mjb/J) spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU), activation of these cells (flow cytometry), cytokine profile (ELISA), and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear. PMID:24771983

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

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

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

  17. 乳源β Casein 125肽的基本特征及促B淋巴细胞增殖作用%Basic characteristics of a human milk-derived peptide β-Casein-125 and its effect on B lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    刘贵友; 万俊; 肖文

    2016-01-01

    The biologic characteristics of β⁃Casein⁃125 peptide were analyzed by Uniprot, SABLE, ProtParam tool and other online databases. The content ofβ⁃Casein⁃125 in colostrum, transition milk and mature milk was mesured by mass spectrometry technology. Furthermore, the effect of β⁃Casein⁃125 peptide in B lymphocyte proliferation was evaluated by MTT assay. The online databases showed that stability coefficient, aliphatic index and grand average of hydropathicity of β⁃Casein⁃125 were 111�43, 111�43 and 0�471, respectively. It indicated that β⁃Casein⁃125 is a hydrophobic stable peptide. The content of β⁃Casein⁃125 was significantly decreased with lactation time, detected by mass spectrometry technology. Moreover, β⁃Casein⁃125 could across the cell membrane of mouse B lymphocytes, and promote their proliferation. β⁃Casein⁃125, a hydrophobic peptide with high stability, could promote lymphocyte proliferation. It was indicated thatβ⁃Casein⁃125 played a critial role in promoting the neonatal immune system maturation.%利用Uniprot、SABLE、ProtParam tool等在线数据库分析β Casein 125肽生物学特征;利用质谱定量技术检测β Casein 125肽在初乳、过渡乳和成熟乳中的含量变化;利用细胞增殖实验方法揭示β Casein 125肽在促进B淋巴细胞增殖中的作用。结果表明:β Casein 125肽的稳定性系数为111�43,脂肪指数和亲水性分别为111�43和0�471,属于疏水性稳定型多肽。质谱定量分析发现:β Casein 125肽含量随泌乳时间变化含量显著降低。β Casein 125肽不仅可以顺利进入小鼠B淋巴细胞,并且可显著促进细胞增殖。β Casein 125肽具有高稳定性和疏水性的特征,可以促进淋巴细胞增殖,提示该肽可能在新生儿免疫系统建立中发挥重要作用。

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

    Energy Technology Data Exchange (ETDEWEB)

    Stenina, M.A.; Potapova, A.A.; Biryukov, A.V.; Skripnik, A.Yu.; Cheredeev, A.N.

    1987-01-01

    The authors study the state of immunoregulatory process in patients with systemic lupus erythematosus at the T-T-cell interaction level and seek to test the possibility of the pharmacological modulation of this process. The proliferative activity of mononuclear lymphocytes, extracted from the blood of ten lupus patients, was assessed by measuring the incorporation of tritiated thymidine into cultures stimulated by phytohemagglutinin, concanavalin, and theophylline. The comparative effects of each of these agents on the immunoregulatory and proliferative activity of the lymphocytes are reported.

  19. 人FasL基因转染成熟树突状细胞对T淋巴细胞增殖和凋亡的影响%Dendritic Cells Genetically Engineered to Express Fas Ligand Regulate T Lymphocyte Proliferation and Apoptosis

    Institute of Scientific and Technical Information of China (English)

    周浩; 王芳; 王毅; 廖端芳; 陈专华; 邢增术; 王刚; 罗志刚; 秦国庆; 李建军; 钱坤; 蒋鸿涛

    2011-01-01

    To investigate the effects of dendritic cells on T lymphocyte proliferation and apoptosis, providing an in vitro model of clinical transplant immunological tolerance. After mature dendritic cells (mDCs) from peripheral blood of healthy adults was successfully transfected with human FasL gene, mDCs were analyzed for the expression of cell surface molecules, antigen presenting function and their apoptosis. Effects of nDCs on T lymphocyte proliferation and apoptosis were further detected based on co-culture of mDCs and T lymphocytes.The results show that, FasL did not significantly change the expression level of mlC's surface molecules CD40,CD80, CD86 and HLA-DR; FasL did not induce apoptosis of mDC. No effects on the antigen presenting function of mDC were observed as well. The miC transfected with FasL decreased stimulation index and increased apoptosis of allogeneic T-lymphocyte significantly. So that, human mDCs transfected with FasL may regulate T lymphocyte proliferation and apoptosis without alteration of cell surface molecules and antigen presentation characteristics on human mDC.%探讨转染人FasL基因的成熟树突状细胞(DC)对异体T淋巴细胞增殖和凋亡的影响,为实现临床器官移植免疫耐受提供初步实验依据.从健康成年人外周静脉血中获得成熟树突状细胞.将人FasL基因成功转染成熟树突状细胞,检测其表面分子的表达和自身凋亡情况,并对其抗原递呈功能进行分析.从异体健康成人外周血中获取T淋巴细胞,将转染成功的树突状细胞与T淋巴细胞混合培养,检测其对T淋巴细胞增殖和凋亡的影响.结果表明:人FasL基因转染没有明显影响成熟树突状细胞表面分子CD40、CD80、CD86和HLA-DR的表达;没有诱导树突状细胞自身发生凋亡;没有影响DC的抗原递呈功能.转染FasL基因后的树突状细胞使异体T淋巴细胞刺激指数明显下降,凋亡增加.因此认为,人FasL,基因转染对成熟树突状细胞的

  20. Estimation of the distribution of low-intensity ultrasound mechanical index as a parameter affecting the proliferation of spermatogonia stem cells in vitro.

    Science.gov (United States)

    Moghaddam, Zeinab Hormozi; Mokhtari-Dizaji, Manijhe; Movahedin, Mansoureh; Ravari, Mohammad Ehsan

    2017-07-01

    Considering the use of physical and mechanical stimulation, such as low-intensity ultrasound for proliferation and differentiation of stem cells, it is essential to understand the physical and acoustical mechanisms of acoustic waves in vitro. Mechanical index is used for quantifying acoustic cavitation and the relationship between acoustic pressure and the frequency. In this study, modeling of the mechanical index was applied to provide treatment protocol and to understand the effective physical processes on reproducibility of stem cells. Due to low intensity of ultrasound, Rayleigh integral model has been used for acoustic pressure computation. The acoustic pressure and mechanical index equations are modeled and solved to estimate optimal mechanical index for 28, 40, 150kHz and 1MHz frequencies. This model are solved in different intensities and distances from transducer in cylindrical coordinates. Based on the results of the mechanical index, regions with threshold mechanical index of 0.7 were identified for extracting of radiation arrangement to cell medium. Acoustic pressure distribution along the axial and radial was extracted. In order to validate the results of the modeling, the acoustic pressure in the water and near field depth was measured by a piston hydrophone. Results of modeling and experiments show that the model is consistent well to experimental results with 0.91 and 0.90 correlation of coefficient (p<0.05) for 1MHz and 40kHz. Low-intensity ultrasound with 0.40 mechanical index is more effective on enhancing the proliferation rate of the spermatogonia stem cells during the seven days of culture. In contrast, higher mechanical index has a harmful effect on the spermatogonial stem cells. Thus, considering cavitation threshold of different materials is necessary to find effective mechanical index ranges on proliferation for the used frequencies. This acoustic propagation model and ultrasound mechanical index assessments can be used with acceptable

  1. Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors.

    Science.gov (United States)

    Palazzo, Maxime; Lombard-Bohas, Catherine; Cadiot, Guillaume; Matysiak-Budnik, Tamara; Rebours, Vinciane; Vullierme, Marie-Pierre; Couvelard, Anne; Hentic, Olivia; Ruszniewski, Philippe

    2013-02-01

    An antiproliferative effect of somatostatin analogs was recently demonstrated. To identify factors associated with tumor control in a group of patients with well-differentiated malignant digestive neuroendocrine tumors treated with lanreotide. A retrospective study was conducted in 68 patients treated with lanreotide alone, with progression-free survival as the primary endpoint. The role of the following factors was searched for by univariate and multivariate analyses: age, sex, mode of discovery, site of the primary tumor, metastatic spread, Ki67 proliferation index, uptake on somatostatin receptor scintigraphy, pretreatment tumor growth, extent of liver involvement, resection of primary tumor, previous treatments, and tumor markers. Tumor progression was observed in 39/68 patients (57.4%). Median progression-free survival was 29 months. On multivariate analysis, a Ki67 proliferation index of up to 5% [hazard ratio (HR)=0.262, P=0.009], pretreatment stability (HR=0.241, P=0.008), and hepatic tumor load of up to 25% (HR=0.237, P=0.004) were significantly associated with disease stability under lanreotide therapy. In patients with well-differentiated malignant digestive neuroendocrine tumors, Ki67 proliferation index of up to 5%, stable disease before treatment, and low-to-moderate hepatic tumor involvement (≤ 25%) are associated with tumor control during lanreotide treatment. These data if confirmed in prospective trials will help in rationalizing the use of somatostatin analogs with antiproliferative intent.

  2. Effect of Excessive Iodine on Immune Function of Lymphocytes and Intervention with Selenium

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiaoyi; LIU Liegang; YAO Ping; YU Dong; HAO Liping; SUN Xiufa

    2007-01-01

    In order to study the effect of excessive iodine on immune function of lymphocytes and the role of selenium supplementation with excessive iodine intake, the changes of T lymphocyte number, ratio of subsets, activity of natural killer (NK) cells and lymphocytes proliferation response were investigated. 150 female BALB/C mice were randomly divided into 5 groups in terms of their body weight (n=30 in each group), and 10 of each group were taken as one batch for test. Mice in the 5 groups were orally administrated with iodine 0 (group Ⅰ ), 1500 (group Ⅱ), 3000 (group Ⅲ),6000 μg/L (group Ⅳ), iodine 6000 μg/L plus selenium 0.3 mg/L (group Ⅴ) respectively for 30 days.Lymphocyte proliferation response, CD4+/CD8+, Th1/Th2 and the activity of NK cells were measured. CD4+/CD8+ was significantly lower, while lymphocyte proliferation response stronger, and Th1/Th2 and the activity of NK cells significantly higher in group Ⅳ than in group Ⅰ (P<0.01).There was no significant difference in all indexes between group Ⅴ and group Ⅰ (P>0.05). It was suggested that excessive iodine as exogenous chemical materials can induce disorders of T lymphocyte immune function in mice. 0.3 mg/L selenium supplementation can protect mice against toxicity induced by 6000 μg/L iodine.

  3. 甜菜碱促进小鼠脾淋巴细胞增殖作用的钙通道机制研究%Calcium channel mechanism by which betaine promotes proliferation of lymphocytes in mice

    Institute of Scientific and Technical Information of China (English)

    季宇彬; 高世勇; 冯小燕; 何立巍

    2009-01-01

    Objective: To study how the way in which betaine promotes the proliferation of mouse spleen lymphocytes is related to calcium channels. Method:BALB/c mice were used for this experiment. Mouse spleen lymphocytes were obtained through in vitro cultivation after they had been separated, and were divided into a negative control group, a ConA group, and 0. 04, 0. 4, 4, and 20 mmol·L~(-1) betaine groups. MTT was used to observe the effect of betaine on the proliferation of mouse spleen lymphocytes; flow cytometry was used to measure the changes in the cell cycle of mouse spleen lymphocytes; and laser confocal scanning microscopy was used to observe the changes in the intracellular [ Ca~(2+) ]; of mouse spleen lymphocytes after betaine or different calcium channel blockers were applied. Result; Betaine was found to promote the proliferation of mouse spleen lymphocytes 12 h after it had been applied in vitro in concentrations of 4 and 20 mmol·L~(-1). It was also found to promote the proliferation of mouse spleen lymphocytes 24 h and 48 h after it had been applied in vitro in concentrations of 0. 04, 0. 4, 4, and 20 mmol·L~(-1), with the effect being most marked for the 4 mmol·L~(-1) group 24 h after its application. It was found to facilitate the entry of mouse spleen lymphocytes from the G_0/G_1 to the S phase 4, 6, 18, and 24 h after it had been applied to mouse spleen lymphocytes in a concentration of 4 mmol·L~(-1) , with the effect being most marked at 18 h after its application. Intracellular [ Ca~(2+) ]; in mouse spleen lymphocytes increased significantly (P < 0.01 ) 6,12, 18 h after 4 mmol·L~(-1) betaine had acted on the lymphocytes, with the effect being most marked at 6 h. The calcium channel blockers nifidipine, dihiazem, mibefradil, and genistein had no effect on the increase of the intracellular [ Ca~(2+) ] ; in mouse spleen lymphocytes due to the application of betaine, while verapamil, mycifradin, heparin, and procaine could block such increase

  4. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress.

    Science.gov (United States)

    Al Ghamdi, Ahmad A; Badr, Gamal; Hozzein, Wael N; Allam, Ahmed; Al-Waili, Noori S; Al-Wadaan, Mohammed A; Garraud, Olivier

    2015-09-15

    Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the selective destruction of pancreatic β cells, followed by hyperglycemia, oxidative stress and the subsequent extensive impairment of immune cell functions, a phenomenon responsible for the development of chronic diabetic complications. Propolis, a natural bee product that is extensively used in foods and beverages, significantly benefits human health. Specifically, propolis exerts antioxidant, anti-inflammatory and analgesic effects that may improve diabetic complications. To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid profile and lymphocyte proliferation and chemotaxis in a streptozotocin (STZ)-induced type I diabetic mouse model. Thirty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice supplemented daily with an ethanol-soluble derivative of propolis (100 mg/kg body weight) for 1 month. First, the induction of diabetes in mice was associated with hyperglycemia and significant decreases in the insulin level and the lymphocyte count. In this context, diabetic mice exhibited severe diabetic complications, as demonstrated by a significant decrease in the levels of IL-2, IL-4 and IL-7, prolonged elevation of the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and reactive oxygen species (ROS) and altered lipid profiles compared with control non-diabetic mice. Moreover, antigen stimulation of B and T lymphocytes markedly reduced the proliferative capacity and chemotaxis of these cells towards CCL21 and CXCL12 in diabetic mice compared with control mice. Interestingly, compared with diabetes induction alone, treatment of diabetic mice with propolis significantly restored the plasma cytokine and ROS levels and the lipid profile to

  5. Indexed

    CERN Document Server

    Hagy, Jessica

    2008-01-01

    Jessica Hagy is a different kind of thinker. She has an astonishing talent for visualizing relationships, capturing in pictures what is difficult for most of us to express in words. At indexed.blogspot.com, she posts charts, graphs, and Venn diagrams drawn on index cards that reveal in a simple and intuitive way the large and small truths of modern life. Praised throughout the blogosphere as “brilliant,” “incredibly creative,” and “comic genius,” Jessica turns her incisive, deadpan sense of humor on everything from office politics to relationships to religion. With new material along with some of Jessica’s greatest hits, this utterly unique book will thrill readers who demand humor that makes them both laugh and think.

  6. Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    M' Bemba-Meka, Prosper [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Faculty of Medicine, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada)

    2007-02-15

    Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0-60 {mu}M), or of nickel subsulfide (Ni{sub 3}S{sub 2}) (0-120 {mu}M), or of nickel oxide (NiO) (0-120 {mu}M), or nickel sulfate (NiSO{sub 4}) (0-120 {mu}M) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 {mu}M but those of Ni{sub 3}S{sub 2} and NiO at 120 {mu}M produced significant increase in the SCE per cell compared to the control value, whereas NiSO{sub 4} failed to produce any such significant increase. Except NiSO{sub 4}, the soluble forms of NiCH, Ni{sub 3}S{sub 2}, and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H{sub 2}O{sub 2} scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H{sub 2}O{sub 2}, the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca{sup 2+}]{sub i}) movement through plasma membranes), or dantrolene (inhibitor of [Ca{sup 2+}]{sub i} release from sarcoplasmic reticulum), or BAPTA (Ca{sup 2+} chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca{sup 2+}]{sub i} is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types

  7. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    Directory of Open Access Journals (Sweden)

    Pongsavee Malinee

    2009-10-01

    Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  8. Effect of Benzene on Proliferation and Apoptosis of Splenic Lymphocytes in Mother Generation and Offspring Mice%苯对母鼠和子鼠脾淋巴细胞的增殖与凋亡影响

    Institute of Scientific and Technical Information of China (English)

    旷亦乐; 李纯颖; 杨双波; 李紫; 吴成秋

    2011-01-01

    Objective To explore the effect of benzene on proliferation and apoptceis of splenic lymphocytes in mother generation and offspring mice. Methods Forty pregnant mice were divided averagely into 4 groups at random. From the 7th day after pregnancy, each of group was exposed to benzene vapour until to parturition (0.0, 5.0, 10.0 and 15.0 mg/m3,respectively), 2 hours par day. At the 1st and 7th days after parturition, 5 mother generation mice end 5 offspring mice of each group were killed to detect the proliferation, cell cycle and apoptosis of splenic lymphocytes in mother generation and offspring mice by MTT assay and flow cytometric analysis. Results During the 1st day and 7th day after parturition, the proliferation of splenic lymphocytes of mother generation and offspring mice in the middle - and high - concentration of benzene groups was inhibited significantly in a concentration-dependent manner (P<O. 05). The cell cycle of splenic lymphocytes of mother generation and offspring mice was blocked in G0/G1 phase in the middle - and high - concentration of benzene groups. The quantity of splenic lymphocytes apoptosis was increased significantly in a concentration- dependent manner in each benzene group (P < 0.05). Conclusion Benzene exposure during pregnancy can damage the immunological function of mother generation mice and offspring mice.%目的 探讨妊娠期接触苯对母鼠及其子鼠免疫功能的影响.方法 40只孕鼠被随机等分为空气对照组和5.0、10.0、15.0 mg/m3三个不同浓度的苯染毒组,各组从孕7 d开始,连续染毒至分娩,每天染毒2 h.分别在分娩后的1 d及7 d,每组取5只母鼠和5只子鼠处死,取脾制备脾淋巴细胞;检测母鼠和子鼠脾淋巴细胞增殖力、细胞周期及细胞凋亡.结果 在分娩后1 d及7 d,中、高浓度苯染毒组母鼠及子鼠的脾淋巴细胞增殖力均低于对照组(P<0.05),并有明显的剂量-效应关系(P<0.05);子鼠与母鼠的淋巴细胞增殖抑制

  9. Initiation of lymphocyte DNA synthesis.

    Science.gov (United States)

    Coffman, F D; Fresa, K L; Cohen, S

    1991-01-01

    The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.

  10. Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes

    NARCIS (Netherlands)

    Finlay, D.K.; Sinclair, L.V.; Feijoo, C.; Waugh, C.M.; Hagenbeek, T.J.; Spits, H.; Cantrell, D.A.

    2009-01-01

    In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)-mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study

  11. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  12. An exploratory study into the effect of exhausting bicycle exercise on endocrine and immune responses in post-menopausal women: relationships between vigour and plasma cortisol concentrations and lymphocyte proliferation following exercise.

    Science.gov (United States)

    van der Pompe, G; Bernards, N; Kavelaars, A; Heijnen, C

    2001-08-01

    It is well-established that bicycle exercise alters the endocrine and immune responses in men, but little information is available for women, especially middle-aged, post-menopausal women. The purpose of our study was to document the endocrine and immune reactivity to exhausting bicycle exercise in post-menopausal women, and to explore whether complaints of fatigue or low vigour are related to these exercise-induced responses. Thirteen healthy post-menopausal women participated in this study. We used a graded exercise protocol to study the kinetics of activation of the endocrine and immune system. We chose to examine hormones related to the hypothalamus-pituitary-adrenal (HPA) system such as adrenocorticotropin hormone (ACTH) and cortisol and hormones related to the pituitary such as prolactin (PRL) and growth hormone (GH). With regard to the immune system, we examined the natural killer (NK) cell activity and pokeweed (PWM)-induced lymphocyte proliferation in addition to changes in peripheral blood cell counts. Our results demonstrate that acute physical stress results in a strong release of ACTH, cortisol, GH and PRL. The bicycle test significantly increased the number of CD3+, CD4+, CD16/56+ (NK cells) and CD8+ cells in our group of post-menopausal women. Interestingly, NK activity did not increase significantly despite an increase in NK cell numbers. PWM-induced lymphocyte proliferation did not change either. In addition, our data support the hypothesis that low vigour in post-menopausal women interferes with the endocrine and immune responses to exhausting exercise. In women with complaints of low vigour we found lower cortisol responses and higher increments in the proliferative capacity of lymphocytes as compared to those with high vigour scores. NK activity was unrelated to exhaustive mood states. These data indicate that endocrine as well as immune system activity changes in response to exhausting exercise in middle-aged, post-menopausal women. In addition

  13. CTLA4Fcε, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation.

    Science.gov (United States)

    Perez-Witzke, Daniel; Miranda-García, María Auxiliadora; Suárez, Nuris; Becerra, Raquel; Duque, Kharelys; Porras, Verónica; Fuenmayor, Jaheli; Montano, Ramon Fernando

    2016-05-01

    Immunoglobulin E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with a fragment of the IgE H-chain constant region. In SDS-PAGE/inmunoblot analyses, CTLA4Fcε appeared as a 70,000 MW polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcε binds to IgE receptors FcεRI and FcεRII/CD23, as well as to CTLA-4 counter-receptors CD80 and CD86. Binding of CTLA4Fcε to FcεRII/CD23 appeared stronger than that of IgE. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcε to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23-specific ELISA, CTLA4Fcε - but not IgE - induced a concentration-dependent reduction of sCD23 in culture supernatants of RPMI-8866 cells. Our results suggest that the simultaneous binding of CTLA4Fcɛ to CD23-CD80/CD86 may cause the formation of multi-molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, so blocking sCD23 generation. CTLA4Fcε caused a concentration-dependent reduction of lymphocyte proliferation in human peripheral blood mononuclear cell samples stimulated in vitro with concanavalin A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4Fcɛ has immunomodulatory properties on human Th2 responses.

  14. 牙髓干细胞MHC分子表达与体外混合淋巴细胞的增殖%MHC molecule expression in dental pulp stem cells and mixed lymphocyte proliferation in vitro

    Institute of Scientific and Technical Information of China (English)

    聂姗姗; 刘佳; 张瑞涵; 王璇; 李伯琦; 孙大磊; 热甫卡提; 刘奕杉

    2014-01-01

    背景:若牙髓干细胞诱导分化后仍然具有与未分化时相似的免疫调节能力,则有可能为组织工程提供同种异体种子细胞来源。  目的:观察牙髓干细胞表面免疫分子的表达以及体外调节淋巴细胞反应的功能。  方法:从C57BL/6小鼠牙髓组织中分离获取牙髓干细胞,体外培养至第2代,流式细胞仪检测免疫分子MHC-Ⅰ、MHC-Ⅱ的表达。以1×105/孔牙髓干细胞刺激异体淋巴细胞,观察细胞增殖情况。以1×105/孔数量的牙髓干细胞或经γ-干扰素作用后的牙髓干细胞加入混合双向淋巴细胞反应体系中,观察淋巴细胞增殖情况。  结果与结论:牙髓干细胞表达MHC-Ⅰ类分子,但未检测到MHC-Ⅱ类分子阳性表达。γ-干扰素刺激48 h后, MHC-Ⅰ表达未见明显增高,MHC-Ⅱ类分子表达明显增高。异体或经γ-干扰素作用的牙髓干细胞均未能刺激淋巴细胞体外增殖。说明牙髓干细胞可在体外调节淋巴细胞增殖反应,有可能成为组织工程或细胞治疗中同种异体细胞来源。%BACKGROUND:If differentiated dental pulp stem cels have immune adjustment ability similar to undifferentiated ones, they could become a new source of alogeneic seed cels in tissue engineering. OBJECTIVE:To study the immunological properties of dental pulp stem cels and their immunomodulatory effects on lymphocytes in vitro. METHODS:Dental pulp stem cels were isolated from mouse dental pulp tissue. Cels at passage 2 were detected using flow cytometry for the expression of MHC-I, MHC-II. Inguinal lymphcels were cultured with alogeneic dental pulp stem cels at a density of 1×105 cels per wel. Dental pulp stem cels at 1×105 cels per wel or interferon-γ-treated dental pulp stem cels were added into the mixed lymphocyte reaction system to observe lymphocyte proliferation. RESULTS AND CONCLUSION: Flow cytometry showed that undifferentiated dental pulp stem cels

  15. Preparation of Mycobacterium polysaccharides and their effect on lymphocyte proliferation%分枝杆菌多糖的制备及对小鼠脾淋巴细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    周莉婷; 赵晶晶; 吴彦卓; 杨仲璠; 姚文兵; 徐明波

    2011-01-01

    目的:制备分枝杆菌多糖并考察其对小鼠淋巴细胞增殖的影响.方法:用苏通培养基培养分枝杆菌,菌体脱脂后,用5种方法提取,比较多糖得率,并用正交试验优化超声提取工艺,再用稀碱提取残渣,粗多糖经Sevag法除蛋白、DEAE-Sepharose Fast Flow层析柱纯化后得到分枝杆菌多糖;用MTT法检测分枝杆菌多糖对小鼠脾淋巴细胞增殖的影响.结果:超声后热水提取多糖得率最高,超声提取的优化工艺是提取时间40 min,固液比为1∶150,超声功率600 W;单因素试验优化的Sevag法除蛋白条件为体积比1∶5,萃取时间为20 min,萃取6次;提取得到的4种多糖组分在6.25~50 mg·L-1范围内均能显著促进脾淋巴细胞的增殖.结论:用本实验工艺成功制备了分枝杆菌多糖,制备物具有刺激小鼠脾淋巴细胞增殖的作用.%Objective: To prepare Mycobacterium polysaccharides (MPS) and determine their effect on lymphocyte proliferation in mice. Methods; Mycobacterium was cultivated in Sauton's medium, and 5 methods were used to extract polysaccharides, and the extraction rates were compared. The ultrasonic extraction was optimized by an orthogonal design. Hot-water extraction residue was extracted in alkaline solution. Crude polysaccharides were purified by deproteinization and DEAE-sepharose Fast Flow chromatography. The effect of polysaccharides on mouse splenic lymphocytes was analyzed by MTT method. Results; The highest polysaccharide yield was obtained by ultrasonic and followed hot-water extraction; the best ultrasonic extraction condition defined by the orthogonal design was extracting 40 min with 150 times solvent and 600 W power. The best deproteiniation condition was extracting 6 times with 1/5 Sevag reagent, 20 min for every time. All the obtained 4 kinds of mycobacterium polysaccharides apparently stimulated the proliferation of mouse splenic lymphocytes at concentrations of 6. 25 ~ 50 mg·L-1. Conclusion

  16. INDEXING AND INDEX FUNDS

    Directory of Open Access Journals (Sweden)

    HAKAN SARITAŞ

    2013-06-01

    Full Text Available Proponents of the efficient market hypothesis believe that active portfolio management is largely wasted effort and unlikely to justify the expenses incurred. Therefore, they advocate a passive investment strategy that makes no attempt to outsmart the market. One common strategy for passive management is indexing where a fund is designed to replicate the performance of a broad-based index of stocks and bonds. Traditionally, indexing was used by institutional investors, but today, the use of index funds proliferated among individual investors. Over the years, both international and domestic index funds have disproportionately outperformed the market more than the actively managed funds have.

  17. Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.

    Science.gov (United States)

    Justo, G Z; Durán, N; Queiroz, M L S

    2003-08-01

    The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

  18. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

    Science.gov (United States)

    Walsh, Catherine J; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; de Wit, Martine; Bonde, Robert K

    2015-04-01

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (pimmune function components, and thus, overall health, in the Florida manatee.

  19. Effects of Trace Element Compound Injection on Lymphocyte Proliferation of Plateau Tibetan Sheep%复方微量元素注射液对高原型藏羊淋巴细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    余劲; 曾朝蓉; 蓝岚; 蒋忠荣; 胡延春

    2014-01-01

    为了探讨微量元素对高原型藏羊细胞免疫功能的影响,并筛选出增强藏羊细胞免疫的复方微量元素制剂的最佳剂量,笔者开展了本试验。将体重为13 kg±1 kg的高原型藏羊随机分成I组(对照组)、II组(低剂量组)、III组(中剂量组)、IV组(高剂量组),分别按0、0.1、0.2、0.4 mL/kg肌肉注射复方微量元素制剂,并用MTT法测定注射后0、15、30、45、60 d藏羊血清中的淋巴细胞增殖率。结果显示:与对照组相比,各试验组的淋巴细胞增殖率均显著或者极显著升高(P<0.05或P<0.01),说明复方微量元素制剂可显著提高高原型藏羊的细胞免疫功能,其中中剂量组(0.2 mL/kg)的效果最好。%The purpose of this experiment was to study the effects of trace element compound injection on cellular immune function and to select the optimal dose. 24 Plateau type of Tibetan sheep (weight of 13 kg ±1 kg) were randomly divided into four groups:I group (control group), II group(low dose group), III group (middle dose group), IV group (high dose group), each group was given intramuscular injection of trace element compound injection with 0, 0.1, 0.2, 0.4 mL/kg body weight respectively. Blood samples were drawn at the day before injecting (recorded as 0 d), after 15 d,30 d,45 d,60 d,and lymphocyte proliferation rates were measured. The results showed that lymphocyte proliferation rates of the low-dose group and high dose group were higher than that of the control group(P<0.05). Lymphocyte proliferation rate of middle-dose group was extremely sig-nificant higher during all the experiment groups (P<0.01). The conclusion was that trace element compound injection could improve cellular immune function of the Plateau Tibetan sheep significant-ly,and the middle dose group (0.2 mL/kg) was the best.

  20. 嵌合锚定T淋巴细胞对肝癌细胞增殖的阻滞效应%Repression Effects of Anchor Chemric T Lymphocytes on Proliferation of Tumor Associated Glycoprotein 72 Positive Hepatocarcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    徐宏勇; 徐立; 李开宗

    2011-01-01

    Objective To investigate the method for generating anchor chemric T lymphocytes that can target tumor associated glycoprotein-72 (TAG72) antigen and analyze their repressive effects on proliferation of TAG72 positive hepatocarcinoma cells. Methods Firstly, peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated. And then, CD8+ T cells were isolated from PBMCs via magnetic activated cell sorting (MACS). These lymphocytes were transfected with recombinant vector, anti-TAG72-scFv-CD28-pcDNA3, through Lipofectamine2000 to gernerate anchor chimeric TAG72-specific CD8+ T cells. SMMC7721 (TAG72 positive) hepatocarcinoma cells were co-cultured with chimeric T lymphocytes and their cell cycles were analyzed by flow cytometry (FCM). Results Anchor chmeric T lymphcytes targetting TAG72 recognized TAG72 positive SMM7721 cells and repressive effects on their proliferation were observed by flow cytometry. Conclusion Anchor chmeric T lymphcytes targetting TAG72 on tumor surface can specifically recognize TAG72 positive hepatocarcinoma cells and may exert repressive effect on their proliferation.%目的 探讨肿瘤相关糖蛋白72(TAG72)靶向性嵌合锚定T淋巴细胞的制备方法,并检测它对TAG72阳性肝癌细胞增殖的阻滞效应.方法 分离外周血单核细胞(PBMC),然后用免疫磁珠法分离得到CD8+T淋巴细胞.将重组真核表达载体anti-TAG72-scFv-CD28-pcDNA3.0采用脂质体介导的细胞转染和细胞培养,以制备TAG72靶向性的嵌合锚定T淋巴细胞;将嵌合锚定T淋巴细胞与TAG72阳性肝癌细胞SMMC7721共培养,通过流式细胞仪检测肝癌细胞的周期变化,分析嵌合锚定T淋巴细胞对肝癌细胞增殖的抑制效应.结果 TAG72靶向性嵌合锚定T淋巴细胞可识别肝癌细胞SMMC7721;用流式细胞仪检测发现,嵌合锚定T淋巴细胞可引起肝癌细胞SMMC7721的增殖阻滞.结论 TAG72靶向性嵌合锚定T淋巴细胞可特异性识别TAG72阳性肝癌细胞SMMC7721并引起其增殖阻滞.

  1. The Inhibitory effects of Hydrocortisone on Proliferation of Mouse T Lymphocytes%氢化可的松对小鼠T淋巴细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    彭新青; 周大杰; 乔玉莉; 韦日明

    2011-01-01

    [Objective] The aim was to investigate effects of Hydrocortisone on proliferation of mouse T lymphocytes. [Method] T lymphocytes separated aseptically from mouse spleen were stimulated in RPMI1640 complete medium plus Con A and transformed. The CD25 and CD69 on the surface of activated T cells as well as their co - expression rate were detected by Flow Cytometry ( FCM). The transformed T cells were divided into two groups; the control group cultured without Hydrocortisone and the experimental groups cultured with different concentration Hydrocortisone. The T cells were counted at different culture times and the growth curves were made. [Result] The CD25 and CD69 on T cells activated by Con A in three days and their co - expression rate reached the highest level, being 73.5% 、58% as well as 32% respectively. The growth curves showed that both groups of T cells proliferation reached to exponential phase of growth cultured at the 2nd day with Hydrocortisone; the activated mouse T cells were inhibited by all of 10-5mol/L、10~6mol/L、10-7mol/L Hydrocortisone without significant difference(P>0.05)among the three concentration groups, and with significant difference compared to the control group(P<0.05). [Conclusion] Hydrocortisone could inhibit proliferation of mouse T lymphocytes at a certain range of concentration, providing an experimental basis for animal model of cell transplantation in inducing immune tolerance.%[目的]探讨氢化可的松对小鼠T淋巴细胞增殖功能的影响.[方法]用淋巴细胞分离液无菌制备小鼠脾淋巴细胞,于RPMI1640的完全培养基中加入ConA后进行转化.用流式细胞仪检测T细胞活化分子CD25和CD69及其共表达率.将转化的淋巴细胞分成不加氢化可的松的对照组和加入不同浓度的氢化可的松组,在各时间点取样计数,绘制其生长曲线.[结果]经ConA刺激3d的T细胞上CD25和CD69分子及其共表达率最高,分别达73.5%、58%和32%.生长曲线显示,

  2. Effects of ginkgolide B on activation, proliferation and apoptosis of murine T lymphocytes in vitro%银杏内酯B对小鼠T淋巴细胞体外活化、增殖与凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    王晓东; 曾耀英; 宋兵

    2011-01-01

    To explore the potential immunomodulatory effects and related mechanisms of ginkgolide B (GB), a known potent antagonist of platelet-activating factor receptor, we investigated the behaviors of T lymphocytes, including activation, proliferation and apoptosis. T lymphocytes were prepared from murine lymph nodes, and then treated with different concentrations of GB before cultivation. Activation and proliferation of T cells were induced by polyclonal activator concanavalin (Con A). Fluorescence conjugated monoclonal antibodies and flow cytometry were used to detect the expression of CD3/CD69 and CD3/CD25; CFDA-SE labeling and flow cytometry were used to trace the proliferation of T lymphocytes and an MTT assay was taken to re-prove. Apoptosis of T cells were induced by dexamethasone (Dex), while [DiOC6(3)/PI] staining and flow cytometry were used to distinguish apoptotic, dead and living cell populations. In a dose-dependent manner, GB (5, 10, and 20 (xmol/L) significantly suppressed the expression of CD69 at 6th h and CD25 at 24th h, as well as inhibited cell proliferation at 48th h after Con A stimulation. To some extent, GB also exhibited protective effect on T lymphocytes from Dex-induced apoptosis. According to these interesting effects of GB on T lymphocytes behaving and functioning, it's quite reasonable to do further studies of GB as a nature occurring immunomodulator candidate.%目的 银杏内酯B (6B)是已知的天然而强效的血小板激活因子(PAF)受体(PAFR)拈抗剂,本文研究GB对小鼠T淋巴细胞活化、增殖及凋亡3大体外行为的影响,初步探讨其潜在的免疫调节作用与机制,从而为临床应用提供可靠的实验依据.方法 分离小鼠淋巴细胞,培养前以不同浓度的GB预孵;以刀豆蛋白A(Con A)诱导细胞的活化与增殖,以荧光抗体双色标记(anti-CD3 mAb-PE/anti-CD69 mAb-FITC、anti-CD3 mAb-PE/anti-CD25 mAb-FITC)结合流式细胞术分别检测T淋巴细胞早、中

  3. 荧光染料CFSE在实验性葡萄膜炎T细胞增殖研究中的应用%Tracking T Lymphocytes Proliferation with Vital Dye CFSE in Experimental Autoimmune Uveitis

    Institute of Scientific and Technical Information of China (English)

    雷松; 毛咏秋

    2009-01-01

    Objective To track T lymphocytes proliferation with vital dye CFSE in experimental autoimmune uveitis (EAU). Methods B10RIII mice were immunized with synthetic peptide of interphotoreceptor retinal-binding protein (IRBP161-180) to develop EAU. The proliferation of IRBP-specific T cell subsets was detected by CFSE staining, fluorescent antibody labeling, and flow cytometry. Results The IRBP-specific T cells divided after 4 days of stimulation with IRBP161-180, halving the fluorescence intensity. The proliferations of CD4~+ and CD8~+ T cells were asynchronous, with CD8~+ T cells dividing more vigorously and having more drop in percentage of parent cells(P<0. 01). Conclusion CFSE-Labeling can detect the proliferation of autoreactive T cells and their subsets in EAU effectively.%目的 探讨荧光染料CFSE在实验性葡萄膜炎(EAU)抗原特异T细胞增殖研究中的应用价值. 方法 以人类光感受器间维生素A类结合蛋白(IRBP)的多肽片段IRBP161-180为抗原,免疫B10RⅢ小鼠使其产生EAU.用CFSE荧光染料标记细胞,结合荧光单抗和流式细胞术,检测T细胞及其亚群在特异抗原刺激下,不同时间点细胞增殖的情况.结果 IRBP161-180刺激4 d后出现T淋巴细胞增殖分裂,表现为CFSE荧光强度的系列减半.使用荧光单抗双标记发现CD4~+ T和CD8~+ T细胞增殖反应不同步,CD8~+ T细胞较CD4~+T细胞增殖分裂更活跃,亲代细胞百分率下降更明显(P<0.01).结论 CFSE荧光标记技术是分析EAU抗原特异性T细胞及亚群增殖分裂的有力工具.

  4. Evaluation of genotoxic activity of tenofovir disoproxil fumarate in human peripheral lymphocytes

    Directory of Open Access Journals (Sweden)

    Kubra Kurt

    2016-06-01

    Full Text Available Purpose: Antiretroviral drugs used in the treatment of HIV (Human Immunodeficiency Virus iinfection, treat by preventing the proliferation of HIV in human body. People with HIV have to use this drugs for lifelong because of inability of the drugs to eradicate the viruses. In this study, we investigated the in vitro genotoxic activity of tenofovir disoproxil fumarate one of the antiretroviral drugs, in human peripheral lymphocytes. Material and Methods: The cells were treated with four different concentrations of tenofovir disoproxil fumarate for 24 and 48 hours. The levels of sister chromatid exchanges, chromosomal aberrations, and micronucleus in the cells were examined for the genotoxic activity of tenofovir disoproxil fumarate. Mitotic index, proliferation index, and nucleer division index of treated cells were also determined for the cytotoxic effect of tenofovir disoproxil fumarate. Results: There was no significant differences in the level of sister chromatid exchanges, chromosomal aberrations, and micronucleus in human lyphocytes treated with all concetrations of tenofovir disoproxil fumarate for all treatment period as compared to control group. Similarly, it was observed that treatment of tenofovir disoproxil fumarate did not affect the mitotic index, proliferation index, and nucleer division index values. Conclusion: As a result, in this study, it is demonstrated that tenofovir disoproxil fumarate did not have genotoxic or cytotoxic effect in the human peripheral lymphocytes. [Cukurova Med J 2016; 41(2.000: 229-235

  5. Onset of the lymphocytic infiltration and hyperplasia preceding the proliferation in F1 mouse lungs from the N-ethyl-N-nitrosourea exposed mothers: Prevention during the lactation period by inositol hexaphosphate

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    Satya Sahay

    2015-01-01

    Full Text Available Maternal exposure to a carcinogen is associated with increased risk of different cancers in the offspring. The foetus is highly sensitive to carcinogens and this contributes to the foetal basis of the onset of disease. The better understanding of the molecular mechanisms involved in the early stage of lung tumourigenesis in the offspring is needed for the newer preventive strategies. We evaluated the effects of N-ethyl-N-nitrosourea (ENU given on the 17th day of gestation and antitumour agent inositol hexaphosphate (IP6 to the mothers at the early stage of lung tumourigenesis in F1 mice. There was no treatment related effects on the litter size or body weight of the F1 mice at the PND12 or 24. Analysis of PCNA, NF-κB (p50, IL-6, COX-2, pSTAT3, STAT3, caspase-3, caspase-9, PARP, Akt signalling and downstream cyclin D1 along with miR-155, suggested the modulation of proliferation, inflammation and apoptosis at PND12 and 24. IP6 administration to the predisposed mothers prevented the proliferation, inflammation and enhanced apoptosis in F1 lung as showed by a reduction in PCNA, NF-κB (p50, IL-6, COX-2, pSTAT3, STAT3, miR-155 and increase in caspases, cleavage of poly (ADP-ribose polymerase. IP6 administration also inhibited the activation of Akt and cyclin D1. Our study shows that tumourigenic changes take place in the lungs of the F1 generation from the carcinogen predisposed mothers even before the onset of tumours and the simultaneous intake of chemopreventive agent during the gestation or lactation period could prevent the lymphocytic infiltration and hyperplasia preceding the tumourigenesis.

  6. 不同外邪对正常及免疫功能低下小鼠脾淋巴细胞增殖能力的影响%Effect of attacks factors on the immunesplenic Lymphocytes proliferation capacity of normal and low immune function mice

    Institute of Scientific and Technical Information of China (English)

    马彦平; 郭彩云; 李俊莲; 李艳彦; 杨琬芳; 李孝波; 王平; 陶功定

    2012-01-01

    Objective: To detect the proliferation capacity of splenic lymphocytes of mice in the cold, cold dampness and hot and humid environment, and discusses the effect of different factors of attacks on the immune functions of mice. Methods: We choose knife bean protein (ConA) induced spleen lymphocyte proliferation, use the MTT method to determine the spleen lymphatic proliferation capacity in mice. Results: ①The mice splenic lymphocytes proliferation capacity of all the attack factors processing groups were significantly lower than the normal group (P<0.01).②All the attack factors processing low immune functions groups compared with low immune function group, the splenic lymphocytes proliferation capacity of wind-cold, cold-dampness low immune function groups reduced significantly (P<0.01); the splenic lymphocytes proliferation capacity of dampness-heat low immune function groups decreasd, but this was not statistically significant. ③The wind-cold low immune function group compared with the wind-cold group, the cold-dampness low immune function group compared with the cold-dampness group, the dampness-heat low immune function group compared with the dampness-heat group, all the mice splenic lymphocytes proliferation capacity significantly reduced (P<0.01). Conclusion: Compared with the normal group, the mice splenic lymphocytes proliferation capacity of all the attack factor processing groups reduced, the mice splenic lymphocytes proliferation capacity of low immune modle groups especially signigicant. The study shows that the three attacks factors of wind-cold, cold-dampness, dampness-heat can make the immune function of mice reduce and cause the happen of the disease easily.%目的:通过检测在风寒、寒湿和湿热环境下小鼠脾淋巴细胞的增殖能力,探讨不同外邪因素对小鼠免疫功能的影响.方法:选择刀豆蛋白(ConA)诱导脾淋巴细胞增殖,采用MTT法测定小鼠脾淋巴细胞增殖能力.结果:①各外邪因素处理

  7. Genotoxic effects of bistratene A on human lymphocytes.

    Science.gov (United States)

    Rojas, E; Valverde, M; Vega, L; Salvador, A; Ramirez, P; Herrera, L A; Watters, D; Lavin, M F; Ostrosky-Wegman, P

    1996-03-01

    Bistratene A, a toxin isolated from the colonial ascidian Lissoclinum bistratum causes a decrease in mitotic index and retardation of lymphocyte proliferation kinetics when it is added at 48 h to 72-h human lymphocyte cultures. In the same cultures, the incidence of sister chromatid exchanges was not altered by this compound. We also observed an increase in the number of polyploid cells in the cultures, and alterations of the beta-tubulin organization by immunocytochemistry with an antibody against beta-tubulin. Bistratene A induces DNA damage in a dose-dependent fashion in leukocytes, as measured by the alkaline single cell gel electrophoresis assay. These results show that bistratene A interferes with microtubule assembly, is cytotoxic and cytostatic, and that it causes DNA damage.

  8. 枸杞多糖对雏鸡淋巴细胞体外增殖及分泌IL-2的影响%Effects of Lycium barbarum Polysaccharide on Cell Proliferation of Chicken Lymphocytes and IL-2 Excretion in vitro

    Institute of Scientific and Technical Information of China (English)

    徐占云; 秦睿玲; 褚耀诚; 李国辉; 李春红; 王丽

    2013-01-01

    This experiment was conducted to investigate the effects of Lycium barbarum polysaccharide (LBP) on cell proliferation of chicken Lymphocytes in vitro. Different concentrations of LBP were added into cultured with plants hemagg-lutinin (PHA) stimulated chicken thymus, spleen and peripheral blood lymphocyte, and cultured with bacteria lipopolysaccharide (LPS) stimulated chicken bursa of Fabricius, peripheral blood lymphocyte, spleen, MTT method and ELISA method were used to determine the lymphocyte proliferation and IL-2 excretion respectively. The results showed that: (1) LBP could stimulate T, B lymphocyte proliferation and IL-2 excretion in certain concentration range and with the increase of the concentration of polysaccharide increase; (2) The OD value of T, B lymphocyte with the source of the same organ were significantly growth trend with chickens dayage growth in same concentration of LBP. (3) The OD value of thymus T lymphocyte and bursa of Fabricius B lymphocyte were higher than in peripheral blood and the spleen T, B lymphocytes with the same concentration LBP and the same day age of chicken. These results indicated that LBP could stimulate T, B lymphocyte proliferation and IL-2 excretion, and the promoting function of lymphocyte proliferation have certain concentration-response, time relationship and organizational correlation.%为探讨枸杞多糖(LBP)对雏鸡T、B淋巴细胞体外增殖的影响,将不同浓度的LBP分别加入到用植物血凝素(PHA)刺激的体外培养的雏鸡胸腺、外周血、脾脏淋巴细胞中,以及用细菌脂多糖(LPS)刺激的体外培养的雏鸡法氏囊、外周血、脾脏淋巴细胞中,分别用MTT比色法和ELISA法测定淋巴细胞增殖的变化以及IL-2的分泌量.结果显示:(1)LBP在一定浓度范围内时,均能刺激T、B淋巴细胞的增殖和促进IL-2的分泌,且随着多糖浓度的增加而增加;(2)LBP对同一器官来源的T、B淋巴细胞的OD值随着雏鸡日龄的

  9. 糖酵解抑制剂3-溴丙酮酸对异基因小鼠混合培养脾细胞增殖的影响及其机制初步研究%Effect of glycolytic inhibitor 3-BrPA on the proliferation and apoptosis of mouse splenic lymphocytes in mixed lymphocytes culture

    Institute of Scientific and Technical Information of China (English)

    周睿卿; 王静; 邱大发; 牛晓敏; 郭子文; 何慧清; 许晓军

    2014-01-01

    Objective To study the effect of glycolytic inhibitor 3-Bromopyruvate (3-BrPA) on the proliferation and apoptosis of mouse spleen lymphocytes and explore its mechanism.Methods An one-way mixed lymphocyte culture (MLC) system was established,including BALB/c mouse spleen cells (H-2d) as stimulator and C57BL/6 mouse spleen cells (H-2b) as responder.With treatment of 3-BrPA at different concentrations (0-200 μmol/L),lymphocyte proliferation capacity was detected by the CCK-8 method,the expression of CD3,CD4,and CD8 by flow cytometry,and the concentrations of cytokine interleukin (IL)-4 and interferon (IFN)-γ in the supernatant by ELISA.Results At a middle or high dose (over 20 μmol/L),3-BrPA displayed a dose-dependent inhibitory effect on lymphocyte proliferation in the MLC system.The 50% inhibitory concentration (IC50) were 48.6,41.2,and 41.9 μmol/L after 24,36,and 48 h culture,respectively.With treatment of 50 μmol/L 3-BrPA,the IFN-γ level [(164.25±20.14) ng/L] was significantly lower,compared with control [(277.61 ± 18.46) ng/L].The IL-4 level [(31.06 ± 6.06)ng/L] was significantly higher,compared with control [(28.64 ± 3.97) ng/L].Consequently,the IFN-γ/IL-4 ratio decreased significantly.Conclusions These results indicate that 3-BrPA had a significant inhibitory effect on the proliferation of mouse spleen lymphocytes cultured in MLC system,accompanied with the Th2-biased secretion of cytokines.%目的 研究糖酵解抑制剂3-溴丙酮酸(3-BrPA)对单向混合培养的异基因小鼠脾细胞增殖的影响及其机制.方法 以BALB/c(H-2d)小鼠脾细胞为刺激细胞,以C57BL/6(H-2b)小鼠脾细胞为反应细胞,建立单向混合淋巴细胞培养(MLC)体系,给予不同浓度3-BrPA(0~200 μmol/L)处理后,采用CCK-8法检测淋巴细胞增殖活性,流式细胞术检测MLC体系中反应细胞CD3、CD4、CD8等表面标志表达,ELISA法检测MLC体系上清中IL-4、IFN-γ等细胞因子水平.结果 CCK-8检测结果显示,高浓度(20

  10. Prognostic value of the apoptotic index analysed jointly with selected cell cycle regulators and proliferation markers in non-small cell lung cancer.

    Science.gov (United States)

    Dworakowska, Dorota; Jassem, Ewa; Jassem, Jacek; Karmoliński, Andrzej; Lapiński, Mariusz; Tomaszewski, Dariusz; Rzyman, Witold; Jaśkiewicz, Kazimierz; Sworczak, Krzysztof; Grossman, Ashley B

    2009-10-01

    In a previous small series of surgically treated non-small cell lung cancer patients (NSCLC), we found that higher apoptotic index (AI) negatively influenced survival (Dworakowska D, Jassem E, Jassem J, Karmolinski A, Dworakowski R, Wirth T, et al. Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression. J Cancer Res Clin Oncol 2005; 131:617-623.). In this study we attempted to verify our previous finding in larger group of 170 NSCLC cases, additionally correlating AI to selected cell cycle regulators as well as a proliferation marker. Apoptosis was assessed with the use of the TUNEL technique, whereas the expression of p53, pRb, mdm2, p21(WAF1/CIP1), cyclin D1 and PCNA were assessed immunohistochemically. The mean and the median AI was 12 and 8, respectively. The expression of p53, pRb, mdm2, p21(WAF1/CIP1) proteins and cyclin D1 was found in 47%, 71%, 37%, 65% and 40% of cases, respectively. The mean and the median PCNA labeling index (PCNA LI) was 34 and 35, respectively. AI was not correlated with any patient characteristic or other tumor markers. In uni- and multivariate analysis AI, analysed separately or jointly with cell cycle regulators and PCNA LI, did not influence disease-free or over-all survival. However, patients with "very high AI/very high PCNA LI" had a particularly poor prognosis (P=0.001). Patients with "very low AI/negative pRb" phenotype survived for a shorter time in comparison to others (P=0.04). In addition, patients with the highest PCNA LI had a worse outcome in comparison to patients with the lowest PCNA LI (P=0.04), especially those with concomitant p53 protein expression (P=0.026) or lacking pRb protein expression (P=0.04). This study demonstrates that joint analysis of several factors involved in apoptosis, proliferation and cell cycle regulation, but not AI alone, might provide additional prognostic information in NSCLC patients.

  11. EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB-1 proliferation index.

    Science.gov (United States)

    Purkait, Suvendu; Sharma, Vikas; Jha, Prerana; Sharma, Mehar Chand; Suri, Vaishali; Suri, Ashish; Sharma, B S; Sarkar, Chitra

    2015-10-01

    Enhancer of zeste homolog 2 (EZH2) mediated down-regulation of CDKN2A/p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A/p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A/p16 status as well as MIB-1 labeling index (LI). Gliomas of all grades (n = 118) were studied using immunohistochemistry to assess EZH2, p16 and MIB-1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion (HD) were both significantly more frequent in high-grade gliomas (HGG). Further, strong EZH2 expression (LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non-deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non-deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB-1 LI, irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs. Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs. Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB-1 LI. Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non-deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed. © 2015 Japanese Society of Neuropathology.

  12. Culture and identification of mouse bone marrow derived DCs that induce T lymphocyte proliferation%小鼠骨髓来源树突状细胞培养鉴定和诱导T淋巴细胞增殖

    Institute of Scientific and Technical Information of China (English)

    吴昆; 拜合提亚·阿扎提; 王文光; 安尼瓦尔·牙生; 王玉杰

    2011-01-01

    Objective:To establish a method of inducing and culturing dendritic cells from mouse bone marrow in vitro,and observe their biological feature and function of stimulating T lymphocytes proliferate in different stages. Methods: Mononuclear cells isolated from mouse bone marrow were induced into dendritic cells by being cultured with GM-CSF and IL-4,and then examined from aspects of morphology,phenotype and function. Results:Modality of mononuclear cells diversified after being cultured in CM-CSF and IL-4 for 3 days,and growthing clustered-liked. When culturing for S days,typical morphology with dendritic processes can be observed. A large number of morphologically typical dendritic cells were observed after culturing for 8 days,under scan electron microscope. DCs displayed typical morphology with dendritic processes and high expressed specific marker of bone marrow derived DC-CD11c and costimulatory molecules of CD40,CD80,CD86 and MHC-Ⅱ. Mature BMDC could stimulate syngenic and allogenic mixed lymphocyte proliferation. Conclusion: A large number of dendritic cells can be generated by culturing the mononuclear cells derived from mouse bone marrow in vitro, and thus will lay a foundation for future research in producing the anti-tumor vaccine.%目的:建立一种体外诱导培养小鼠树突状细胞(DCs)的方法,并观察其不同生长阶段生物学形态及刺激淋巴细胞增殖的能力。方法:联合应用粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)诱导培养小鼠骨髓单个核细胞向DCs分化,并从形态学、表型及功能方面对其加以检测。结果:用GM-CSF和IL-4诱导培养小鼠骨髓来源的单核细胞,3 d后可见细胞形态改变,并呈集簇生长,培养至5 d可见典型的树突状突起,体外诱导培养8 d后获得大量成熟的DCs,扫描电镜可见典型的树突状细胞形态,高表达骨髓来源DCs特异性标记CD11c和共刺激分子CD40、CD80、CD86和MHC-Ⅱ

  13. The Role of HIV-1 in Affecting the Proliferation Ability of HPCs Derived From BM.

    Science.gov (United States)

    Guo, Xiaolin; He, Sijia; Lv, Xiaoyi; Ding, Haibo; Li, Sha; Kang, Jing; Liu, Jing; Qin, Chaolong; Geng, Wenqing; Jiang, Yongjun; Shang, Hong

    2016-04-15

    HIV-1 causes chronic infection characterized by the depletion of CD4+ T lymphocytes and the development of AIDS. Current antiretroviral drugs inhibit viral spread, but they do not lead to a full immune recovery. Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitor cells (HPCs) give rise to all blood and immune cells, and in HIV infection, hematological abnormalities frequently occur in patients. Here, we used bone marrow samples from HIV-1-infected people to study the relationship between the proliferation ability of HSCs/HPCs and peripheral CD4+ T lymphocytes. Three indexes were used to reflect the proliferation ability of HSCs and HPCs: (1) colony-forming units of bone marrow mononuclear cells (BMMCs), (2) amplification of CD34+ cells purified from bone marrow mononuclear cells, (3) expression of HOXB4 and HOXA9 in CD34+ cells. We observed a direct correlation between peripheral number of CD4+ T lymphocytes and the HSCs/HPCs proliferation ability in our study. We also compared HIV-infected patients with or without antiretroviral therapy (ART). Our results demonstrated that after antiretroviral therapy, CD4+ T-cell recovery and HPCs proliferation ability are correlated. Our findings have implications in understanding whether bone marrow-derived HPCs can supplement for the loss of CD4+ T lymphocytes during HIV-1 infection.

  14. 59. Protectivc effect of melatonin on genetic damage by chemical mutagen and the influence on cell prolife-ration kenetics

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: In this study, we observed the effect of melatonin on the frequency of sister chromatid exchange, micronucleus formation of binuclear cell in lymphocyte from human peripheral blood in vitro, micronucleus formation of mouse bone marrow polycychromatic erythrocyte in vivo, which were induced by chemical mutagen, and lymphocyte proliferation kenetics in vitro. Methods: ① Lymphocytes were cultured in vitro in the presence of 0.01,0.10,1.00 mmol/L melatonin, mitomycin C(MMC) (positive control), 0.5% ethanol (negative control)and 0.01,0.10,1.00 mmol/L melatonin plus MMC for 72 h at 37℃±1℃. Lymphocytes were examined for the frequence of SCE, mitotic index, cell proliferation cycle, cell cycle ratio and proliferation index. ② Lymphocytes were cultured in vitro in the presence of 0.01,0.10,1.00 mmol/L melatonin, mitomycin C(MMC) (positive control), 0.5% ethanol (negative control) and 0.01,0.10,1.00 mmol/L melatonin plus MMC for 44 h at 37℃±1℃. Then each culture was given cytochalasin B, which was cultured to 72 h. Binuclear lymphocytes were examined for the micronucleus rate. ③ The mice were administered with 0.1, 1.0,10.0 mg/kg*bw melatonin and distillated water (negative control) respectively for 7 d, then were given melatonin plus cyclophosphamide (CP) (positive control) for 2 d since the eighth day. The rate of micronulclei of mouse bone marrow polycychromatic erythrocyte was examined. Results: ① The frequences of sister chromatid exchange of lymphocytes which were cultured in the presence of 0.01,0.10,1.00 mmol/L melatonin compared with negative control exhibited no statistical significance. ② The SCE of cells treated with melatonin plus MMC compared with positive control were markedly decreased. ③ The mitotic indices of lymphocytes cultured in the presence of 0.10,1.00 mmol/L melatonin were lower than negative control. The proliferation index was significant lower than negative control only in the culture exposed to 1.00 mmol

  15. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  16. Peroxisome proliferator-activated receptor (PPAR) delta genetic polymorphism and its association with insulin resistance index and fasting plasma glucose concentrations in Chinese subjects.

    Science.gov (United States)

    Hu, C; Jia, W; Fang, Q; Zhang, R; Wang, C; Lu, J; Xiang, K

    2006-12-01

    Previous studies have shown that the peroxisome proliferator-activated receptor delta (PPARD) genetic polymorphism affects cholesterol metabolism in Whites. This association was not observed in a Korean population in a separate study, but this study showed a link between the PPARD polymorphism and body weight and fasting plasma glucose. The purpose of this study was to determine whether polymorphisms of PPARD influence glucose and cholesterol metabolism in Chinese subjects. We investigated the association between the polymorphism (-87T/C) of the human PPARD gene and phenotypes related to body weight, insulin sensitivity, glucose and lipid metabolism in Chinese subjects. Unrelated Chinese subjects (n = 663) in Shanghai were studied; 287 had newly diagnosed Type 2 diabetes mellitus and 376 were non-diabetic control subjects over 40 years old. Clinical parameters were collected and genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. In normal glucose tolerant (NGT) subjects, the C allele carriers had higher fasting plasma glucose concentrations (P = 0.0078) and a lower insulin sensitivity index (ISI) (P = 0.0365). The C allele carriers also showed higher concentrations of low-density lipoprotein cholesterol (P = 0.0261) and percentage of body fat (P = 0.0357). There was a trend towards higher visceral adiposity in C allele carriers, but the difference was not significant (P = 0.0830). In diabetes patients, similar results were detected for plasma glucose concentrations (fasting plasma glucose P polymorphism is associated with higher fasting plasma glucose concentrations in both NGT and diabetic subjects, largely due to impaired insulin sensitivity.

  17. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Science.gov (United States)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  18. Peroxisome proliferators-activated receptor γ2 Pro12Ala variant is associated with body mass index in non-alcoholic fatty liver disease patients.

    Science.gov (United States)

    Gupta, A C; Chaudhory, A K; Sukriti; Pande, C; Sakhuja, P; Singh, Y; Basir, S F; Sarin, S K

    2010-12-01

    Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and commonly associated with insulin resistance and metabolic syndrome (MS). Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor abundantly expressed in adipocytes and plays a key role in the regulation of adipocyte differentiation, lipid and glucose homeostasis. Pro12Ala variant has been earlier associated with obesity, type 2 diabetes and MS. The present study aimed to determine the genotype frequencies of the Pro12Ala variant in NAFLD patients and any further association with other phenotype in the patients. Ninety-eight NAFLD patients and 280 matched controls were genotyped for presence of the Pro12Ala variant. Genomic DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism using Bst-UI was performed for the detection of C-G change at codon 12 position of PPAR γ2 gene. Genotype and allele frequencies were compared between patients and controls. The Hardy-Weinberg equilibrium was tested by comparing expected/observed genotype frequencies by χ(2) test. The frequencies of Pro/Ala genotype were comparable between NAFLD patients and controls. In the controls, 213 (75.7%) were homozygous for the wild-type (Pro/Pro) genotype and 67 (23.9%) were heterozygous (Pro/Ala). In NAFLD patients, genotypic distribution of wild type, heterozygous and homozygous were 63 (64.3%), 34 (34.7%) and 1 (1%), respectively. Heterozygous genotype was found to be significantly higher in the patients (P = 0.01). We also analyzed related phenotypic association of the patients with Pro12Ala genotype. We observed that the Pro12Ala (heterozygous) genotype was significantly higher in the patients who had body mass index >25 kg/m(2) (P = 0.025). Pro12Ala variation of the PPAR γ2 gene is associated with NAFLD and might play a role in the pathogenesis of NAFLD.

  19. Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis.

    Science.gov (United States)

    Puttaswamy, Naveen; Pavan Kumar, G S; Al-Ghorbani, Mohammed; Vigneshwaran, V; Prabhakar, B T; Khanum, Shaukath Ara

    2016-05-23

    Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compound's effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future.

  20. 模拟微重力环境下虫草多糖促进淋巴细胞增殖和CD分子表达的实验研究%Cordyceps Sinensis Enhances Lymphocyte Proliferation and CD Markers Expression in Simulated Microgravity Environment

    Institute of Scientific and Technical Information of China (English)

    郝彤; 王妍; 李俊杰; 杜芝燕; 段翠密; 王滟濛; 王常勇; 宋锦苹; 王林杰; 李莹辉

    2012-01-01

    This study was aimed to explore the effect of cordyceps sinensis enhancing lymphocyte proliferation and surface CD marker expression in simulated microgravity environment. The splenic lymphocytes were separated from mice and cultured in the rotary cell culture system simulated microgravity environment. The cells were treated with different concentration of cordyceps sinensis solution (0, 6.25, 12.5, 25 and 50 μg/ml) for 24, 48 and 72 h respectively, then the cells were harvested, and analyzed for cell proliferation and the expression of cell surface markers(CD4 and CD8). The results showed that under simulated microgravity environment, the lymphocyte proliferation was inhibited. When the concentration of cordyceps sinensis was 25 or 50 μg/ml, the lymphocyte proliferation, CD4 and CD8 expressions all increased, but 50 μg/ml cordyceps sinensis could inhibit the proliferation ability with the time prolonging. It is concluded that the suitable concentration of cordyceps sinensis displayed the ability to enhance the lymphocyte proliferation and CD marker expression in simulated microgravity environment. These results may be valuable for screening drugs which can be potentially against immunosuppression under simulated microgravity.%本研究旨在探索旋转式细胞培养系统(RCCS)模拟微重力环境下虫草多糖促进淋巴细胞增殖和表面CD分子表达的作用.体外分离培养小鼠脾淋巴细胞,在RCCS模拟微重力环境中分别添加6.25、12.5、25和50 μg/ml的虫草多糖溶液培养,在24、48和72 h检测虫草多糖对淋巴细胞增殖及表面CD分子表达的作用.结果表明,模拟微重力环境抑制了淋巴细胞的增殖能力,25和50 μg/ml虫草多糖对淋巴细胞的增殖和CD4、CD8的表达均具有促进作用,但50μg/ml虫草多糖促进淋巴细胞增殖的作用随对间延长变为抑制作用.结论:适宜浓度范围内的虫草多糖具有对抗模拟微重力环境下淋巴细胞增殖能力下降和表

  1. 急性脑卒中病人T淋巴细胞严群变化与改良Barthel指数评分相关分析%Changes of T lymphocyte subpopulation and its relationship with Modified Bobath score in index stroke

    Institute of Scientific and Technical Information of China (English)

    张晓玲; 黄俊军; 裘秀兰; 王志刚; 殷新光

    2002-01-01

    Objective To analyze the correlation of changes of T lymphocyte subpopulation and Modified Bobath index in acute stroke.Method Peripheral blood CD3+ ,CD4+ ,CD8+ ,CD16+ 56+ and ratio of CD4+ /CD8+ were measured using bicolor fluorescent monclonal antibody and flow cytometry and compared with those of 23 healthy controls. Simultaneously,relationship between modified Bobath index and changes of T lymphocytes subpopulation was analyzed.Result Compared with healthy controls, peripheral blood percent of CD3+ ,CD4+ of subjects with acute stroke was marked lower,which was positively correlated with modified Bobath index.Conclusion Immune response is involved in development of acute cerebrovascular diseases.Improving immune function is important for prevention and treatment of cerebrovascular diseases.

  2. Effects of housefly maggots extracts on the proliferation and the CD4+/CD8+ ratio of mouser splenic lymphocytes in vitro%罗仙子提取物对小鼠脾淋巴细胞的体外增殖及CD4+/CD8+比例的影响

    Institute of Scientific and Technical Information of China (English)

    许银叶; 褚夫江; 吴玉萍; 金小宝; 朱家勇

    2013-01-01

    目的 研究罗仙子提取物(housefly maggots extracts,HME)对正常小鼠脾淋巴细胞的体外增殖,以及对小鼠淋巴细胞亚群CD4+/CD8+比例的影响.方法 不同浓度的罗仙子提取物对刀豆蛋白A(concanavalin A,ConA)体外处理的小鼠脾T淋巴细胞作用,初步确定其发挥作用的最佳浓度.采用MTT法检测罗仙子提取物在不同的时间点对ConA诱导的小鼠脾淋巴细胞的增殖能力,运用流式细胞仪检测细胞周期的分布以及CD4+/CD8+比例.结果 罗仙子提取物浓度为40 μg/mL,作用48 h后,能明显促进ConA 诱导的小鼠脾淋巴细胞增殖,并且能降低G0/G1期细胞的百分比以及升高S期和G2/M期细胞的百分比,并以48 h效果最明显.能使CD4+、CD4+/CD8+比例降低.结论 罗仙子可能通过免疫调节作用影响动脉粥样硬化.%Objective To study the effects of housefly maggots extracts ( HME ) on the proliferation and the CD4+/CD8+ ration of mouse splenic lymphocytes in vitro. Methods Mouse splenic lymphocytes stimulated by con-canavalin A ( ConA ) were treated with different concentrations of HME. The effects of splenocyte proliferation were assessed by MTT in order to select the most effective concentration of HME. Using the most effective concentration, splenic lymphocytes were treated with HME at different time points. Splenocyte cell cycle distribution and the CIM + /CD8 + ratio were observed by flow cytometry. Results HME of 40μg/mL notabty promoted the proliferation of splenic lymphocyte after cultivation for 48 hours, reduced the G0/G1 phase cells and raised the S and G2/M phase cells. HME could also reduced the CD4+ , CD8 + and CD4 + /CD8+ ratio. Conclusion HME regulates immue functions in atherosclerosis.

  3. 氧化苦参碱抑制二硝基氟苯所致小鼠接触性皮炎及淋巴细胞增殖%Restraint-effect of Oxymatrine on mouse's allergic contact dermatitis stimulated by DNFB and lymphocyte proliferation stimulated by Con A

    Institute of Scientific and Technical Information of China (English)

    陈明亮; 伍斌; 谢红付; 张江林; 杜乾君; 李建国; 李罗丝

    2006-01-01

    [Objective] To explore the restraint-effect of oxymatrine (OMT)on allergic contact dermatitis (ACD)and lymphocyte proliferation. [Methods] 1.To build up an ACD mouse model stimulated by DNFB and then to perform intraperitoneal injection with different dosages of OMT, PBS and hydrocortisone(HCT), To observe the curative effect by examining the swelling degree of mice auricles. 2. Dyed by Carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE) and then flow cytometer was used to examine the fluorescence intensity changes of lymphocyte co-influenced by polyclonal stimulator Concanavalin A (Con A) and OMT. Whereafter, analyze the efficacy of OMT on mouse lymphocyte proliferation by related software. [Results] 1. Comparing with PBS group, OMT possesses much stronger restraint-effect on ACD that caused by DNFB and depends on its injection dosage. Its restraint-effect is equivalent to the HCT of the same dosage, but brings fewer side effects. 2. In vitro expenment, it proves that OMT has the effects to restrain the proliferation of mice's lymphocyte depending on its concentration in substrate as it behaves differently in group 500, 125 and 31 μg/ml. [Conclusion] OMT possesses the obvious effect of restraining the ACD stimulated by DNFB; OMT is a kind of immunosuppressor.%目的 探讨氧化苦参碱(OMT)对二硝基氟苯(DNFB)所致小鼠变应性接触性皮炎(ACD)的抑制作用及小鼠淋巴细胞增殖的影响.方法 建立DNFB所致小鼠ACD模型,以不同剂量的OMT、PBS、氢化可的松(HCT)进行腹腔注射,检测小鼠耳廓肿胀度变化;利用羧基荧光素乙酰乙酸(CFDA-SE)染色,流式细胞术检测OMT对小鼠淋巴细胞增殖的影响.结果 OMT对DNFB所致小鼠ACD呈剂量依赖性抑制作用,且与同等剂量HCT作用效果相似,但副作用明显减小;体外实验证明,在500、125和31 μg/mL组OMT对小鼠淋巴细胞增殖呈剂量依赖性抑制.结论 OMT对DNFB所致小鼠ACD有显著的抑制作用,而且抑制小鼠淋

  4. Capsaicin from chili (Capsicum spp. inhibits vascular smooth muscle cell proliferation [v1; ref status: indexed, http://f1000r.es/4yk

    Directory of Open Access Journals (Sweden)

    Rongxia Liu

    2015-01-01

    Full Text Available Accelerated vascular smooth muscle cell (VSMC proliferation is implied in cardiovascular disease and significantly contributes to vessel lumen reduction following surgical interventions such as percutaneous transluminal coronary angioplasty or bypass surgery. Therefore, identification and characterization of compounds and mechanisms able to counteract VSMC proliferation is of potential therapeutic relevance. This work reveals the anti-proliferative effect of the natural product capsaicin from Capsicum spp. by quantification of metabolic activity and DNA synthesis in activated VSMC. The observed in vitro activity profile of capsaicin warrants further research on its mechanism of action and potential for therapeutic application.

  5. Comparison of the effects of polysaccharides from wood-cultured and bag-cultured Ganoderma lucidum on murine spleen lymphocyte proliferation in vitro%段木栽培及袋栽灵芝多糖对体外培养小鼠脾淋巴细胞增殖活性的比较

    Institute of Scientific and Technical Information of China (English)

    曹立珍; 林志彬

    2003-01-01

    目的比较段木栽培灵芝多糖(wood-cultured Ganoderma lucidum polysaccharides, Gl-PS-WC) 及袋栽灵芝多糖(bag-cultured Ganoderma lucidum polysaccharides, Gl-PS-BC)对体外培养小鼠脾淋巴细胞增殖活性的影响,探讨袋栽灵芝多糖替代段木栽培灵芝多糖的可能性. 方法检测两种灵芝多糖对混合淋巴细胞培养(MLC)反应的影响;观察对刀豆蛋白A (Con A)、细菌脂多糖(LPS)诱导淋巴细胞增殖的影响以及对环孢素A (CsA)、丝裂霉素C(Mit C)、足叶乙苷(VP-16) 等抑制MLC反应的影响.结果当质量浓度为0.2~12.8 mg*L-1时,两种灵芝多糖均可促进MLC反应,增强Con A或LPS诱导的淋巴细胞增殖,并拮抗CsA, Mit C或VP-16对MLC反应的抑制作用.未发现两种多糖之间有显著性差异.结论 Gl-PS-WC及Gl-PS-BC对体外培养脾淋巴细胞的增殖活性有类似作用.%Aim To compare the influences of wood-cultured Ganoderma lucidum polysaccharides (Gl-PS-WC) and bag-cultured Ganoderma lucidum polysaccharides (Gl-PS-BC) on the proliferation activities of murine spleen lymphocytes in vitro, and investigate whether Gl-PS-BC can be substituted for Gl-PS-WC. Methods Mixed lymphocyte culture (MLC) reaction, lymphocyte proliferation induced by concanavalin A (Con A, 1 mg*L-1) or lipopolysaccharide (LPS, 5 mg*L-1), MLC reactions inhibited by immunosuppressive drugs, cyclosporine A (CsA, 0.1 mg*L-1), mitomycin (Mit C, 0.1 mg*L-1), or antitumor drug, etoposide (VP-16, 0.1 mg*L-1), were detected in the presence or absence of Gl-PS-WC and Gl-PS-BC in the concentration range of 0.2-12.8 mg*L-1. Results Two kinds of polysaccharides were shown to promote MLC in the range of 0.2-12.8 mg*L-1, increase lymphocyte proliferation induced by Con A or LPS and antagonize the inhibitory effects of CsA, Mit C or VP-16 on MLC. No significant difference was observed between these two kinds of polysaccharides in selected concentrations. Conclusion Gl-PS-WC and Gl-PS-BC showed similar effects

  6. Developmental changes in cell proliferation and apoptosis in the normal duck thymus.

    Science.gov (United States)

    Fang, J; Cui, H; Peng, X; Chen, Z; He, M; Tang, L

    2011-12-01

    Cell proliferation and apoptosis in the normal duck thymus during embryonic and post-embryonic development were studied. The flow cytometry assay shows that the level of G(0)/G(1) thymic cell population and the proportion of apoptotic cells increased with age, while the levels of S phase, G(2) + M phase and the proliferating index decreased with age. Proliferation cell nuclear antigen (PCNA) was mainly detected in the nuclei of lymphocytes. The number of PCNA-positive cells in the cortex and medulla significantly decreased with age. Transferase-mediated dUTP nick-end labelling (TUNEL) reaction stained apoptotic bodies in the cytoplasm of macrophages and free apoptotic bodies or nuclei with condensed chromatin in lymphocytes. The number of TUNEL-positive cells in the cortex and medulla markedly increased with age. The amount of proliferation and apoptotic cells in the thymic cortex was higher than that in the medulla. The balance between proliferation and apoptosis in the duck thymus may account for the process of thymic development and involution.

  7. Primary cutaneous CD4 positive small/medium T-cell lymphoma with high proliferation index and CD30-positive large lymphoid cells.

    Science.gov (United States)

    Zhang, Ling; Shao, Haipeng

    2013-08-01

    Primary cutaneous CD4 positive small/medium pleomorphic T-cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T-cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T-cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30-positive large lymphoid cells, and few infiltrating CD8 positive T-cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T-cell markers bcl-6 and PD-1. There were approximately 20% CD30-positive large lymphoid cells, and Ki-67 showed a moderately high proliferation rate (~40%), mostly in the large lymphoid cells. CD8 infiltrating T-cells were few (cells that followed an indolent clinical course. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats

    Institute of Scientific and Technical Information of China (English)

    Shan-shan SONG; Bei HUANG; Qing-tong WANG; Yu-jing WU; Jing-jing FU; Yun-fang ZHANG; Yan CHANG

    2013-01-01

    Aim:To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function.Methods:SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad.After the onset of AA,the rats were injected BF02 (1,3,or 9 mg/kg,sc) every 3 d for a total of 15 d.Intragastric administration of methotrexate (MTX,0.5 mg/kg,every 3 d for a total of 15 d) was taken as the positive control drug.Arthritis index,swollen joint count,ankle joint histopathology,spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats.T lymphocyte function was assessed by measuring T lymphocyte cytokine levels,IL17 and TNF-α mRNA expression levels,and percentage ofT lymphocyte subsets.Results:in the AA rats,remarkable secondary inflammatory responses exhibited,accompanied by significantly higher levels of IL-1,IL-6,TNF-α,IL-17,LTα,RANKL,and MMP-13.The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats.The percentages of CD3+CD4+ and CD4+CD25+ T lymphocytes were increased,whereas the percentages of CD4+CD62L+ and CD4+CD25+FoxP3+ T lymphocytes were decreased.Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index,swollen joint count and arthritis global assessment.Moreover,both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation,and blocked the above mentioned aberrance in T lymphocyte cytokine levels,IL17 and TNF-α mRNA expression,and percentages of T lymphocyte subsets.Conclusion:BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.

  9. 2,4-二硝基氯苯诱导超敏反应性皮炎小鼠淋巴细胞增殖与活化研究%Research on the proliferation and activation of lymphocyte of 2,4-dinitrochlorobenzene-induced hypersensitivity dermatitis mice

    Institute of Scientific and Technical Information of China (English)

    纪玉青; 贾强; 赵雪铮; 孟涛; 李园园; 李红丽; 戴宇飞

    2014-01-01

    % vs(25.70±1.47)%,(13.38±0.98)% vs(18.53±0.93)%,(7.23±0.74)% vs (10.20±0.30)%,P <0.05],耳后淋巴结 T 淋巴细胞比例、CD4+细胞比例和 CD4+/CD8+比值均低于对照组[(25.20±1.22)% vs(39.40±2.53)%,(8.20±0.66)% vs(31.30±2.84)%,(0.76±0.35)vs(5.29±1.17), P<0.05],CD8+细胞比例高于对照组[(10.90±1.31)% vs(6.20±1.99)%,P<0.05]。高剂量组耳后淋巴结CD4+细胞比例和 CD4+/CD8+比值均低于低剂量组[(8.20±0.66)% vs(20.30±2.60)%,(0.76±0.35) vs (2.64±0.03),P<0.05]。结论 T淋巴细胞介导的细胞免疫在 DNCB诱导的超敏反应性皮炎中起重要作用, CD8+细胞是主要的效应性T淋巴细胞,CD44和CD62L表达可作为T淋巴细胞活化检测指标。%Objective To investigate the lymphocyte proliferation and activation in the 2,4-dinitrochlorobenzene( DNCB)-induced hypersensitivity dermatitis mice model. Methods Specific pathogens free 8-12 week-old female C57BL/6 mice were randomly divided into control group,low- and high-dose groups,6 mice per group. Mice in 3 groups were induced daily with 100 μl mass-to-volume ratio of 0. 00%,0. 50% and 1. 00% DNCB respectively on back skin on day 1-3,no special treatment on day 4,and then stimulated once on the dorsum of left ears on day 5 with 25μl mass-to-volume ratio of 0. 25%,0. 25% and 0. 50% DNCB respectively,24 hours later the auricle allergy symptoms were observed. Flow cytometry was adopted to detect the lymphocyte proliferation,activation and subpopulations of spleens( SPs)and auricular lymph nodes( ALNs). Results The left ears of mice were swelling and angiectatic in high dose group,while symptoms were not observed in the control and low dose groups. The grade of ear swelling in high dose group was higher than that in the control[(5. 30 ± 2. 04)vs(0. 50 ± 0. 49)mg,P<0. 05]. Both the organ coefficients of SPs and ALNs in low- and high

  10. 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.

  11. 白藜芦醇对小鼠CD4+T细胞增殖、凋亡和亚群作用研究%Effects of resveratrol on the proliferation, apotosis and subsets distribution of murine CD4+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    王卓龙; 曾小峰; 李梦涛

    2013-01-01

    The purpose of the study is to investigate the effect of resveratrol (Res) on the proliferation,apotosis and subsets distribution of murine CD4+ T lymphocytes.Splenic mononuclear cells (SMC) from specific pathogen free (SPF) Balb/c mice (female,age 9-10 weeks) were cultured with Res (0,20,40,or 80 mmol/L) for 30 min in vitro,then cocultured with Ionomycin and PMA for 1 h for activation,followed by cultivation with protein transporting inhibitor Golgiplug for 4-6 hours.IL-4 and IFN-γ levels in the cultured cells were detected using intracellular cytokine staining with flow cytometry.On the other way,freshly isolated CD4+T lymphocytes using magnetic cell sorting were cultured with Res (0,10,20,or 40 mmol/L) for 36 hours.Then the cells were stained with PI and Annexin V and assayed using flow cytometry.For detecting the proliferation,CD4+T lymphocytes were stained withCFSE and cocultured with anti-CD3,anti-CD28 and IL-2 and Res (0,10,20,or 40 mmol/L) for 4 days in vitro.The results showed that Res (≥20 mmol/L) decreased IFN-γ levels and proliferation of CD4+T lymphocytes significantly in a dose-dependent manner,while Res (≥ 10 mmol/L) induced CD4+T lymphocytes apoptosis significantly in a dose-dependent manner.Thus we concluded that Res can inhibit proliferation and Th1 subset differentiation of murine CD4+ T lymphocytes and induce CD4+ T lymphocyte apoptosis in a dose-dependent manner.%目的 研究白藜芦醇对小鼠CD4+T细胞增殖、凋亡和亚群的影响.方法 Balb/c鼠(SPF,雌性,9~10周龄)脾脏单个核细胞(SMC)与不同浓度(0、20、40、80 mmol/L)白藜芦醇共培养30 min,加离子霉素和PMA共培养1h后,再加蛋白质转运阻断剂Golgiplug继续共培养4~6 h,收集细胞采用胞内细胞因子染色法结合流式细胞术检测IL-4和IFN-γ情况.免疫磁珠法从SMC分选CD4+T细胞.CD4+T细胞与不同浓度(0、10、20、40 mmol/L)白藜芦醇、抗CD3/抗CD28抗体和IL-2共培养,4d后收集细胞采用流式细

  12. The Related Glycoside Monomer of Liuwei Dihuang Decoction and Proliferation of Splenic Lymphocytes in Mice%六味地黄汤相关苷类单体对小鼠脾淋巴细胞增殖作用的研究

    Institute of Scientific and Technical Information of China (English)

    刘继平; 兰洲; 傅强; 罗建光; 马世平; 孔令义

    2011-01-01

    . Results: Proliferative activities of cells that were treated with paeoniflorin (10-5M), loganin (10-7 ~10-5M) and morroniside (10-7 ~10-5 M) were promoted without ConA or LPS; LPS - induced proliferation of B lymphocytes was significantly promoted by paeoniflorin (10-5M), loganin (10-7M), morroniside (10-7 ~10-5M) and aucubin (10-5M); ConA - induced proliferation of T lymphocytes was markedly enhanced by paeoniflorin (10 -7 ~ 10-6 M) , morroniside (10~7 ~10-5M) and aucubin (10-7 ~10-3M), diosgenin played a certain role in promoting lymphocyte proliferation, but there was no significant difference. Conclusion; Paeoniflorin, diosgenin, loganin, morroniside and aucubin in Liuwei Dihuang decoction can enhance the proliferative activities of mice splenic lymphocytes to different degrees. The effect of morroniside on proliferative activity of lymphocytes is stronger than the effects of other compounds.

  13. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    Directory of Open Access Journals (Sweden)

    Hernández-Montes Jorge

    2012-05-01

    Full Text Available Abstract Background Most infections with human papillomavirus (HPV are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL from low-grade squamous intraepithelial lesions (LSIL patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when

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

    Science.gov (United States)

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  15. Expression of B7-H4 gene from mouse in eukaryofic system and its suppressive effect on proliferation of lymphocytes cell%小鼠B7-H4基因的真核表达及其对淋巴细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    李丽; 胡为民; 王朝莉; 杨致邦

    2012-01-01

    Objective To provide subjects for lucubrating the effect of B7-H4 on T cell activation and graft rejective reaction through cloning and constructing the eukaryotic expression vector encoding the gene of extracellular region of B7-H4 from mouse, and investigate the effect of B7-H4 on the proliferation of lymphocytes in vitro. Method The total RNAs of mouse lung and spleen were extracted and cDNA was transcribed from RNA using RT-PCR technique. The gene of extracellular region nf B7-H4 was amplified according to the template of cDNA by PCR. The amplified cDNA was imported into pGEM-T Easy vector to construct TA-mB7-H4 plasmid. The plasmid was cut by restriction enzyme of XbaⅠ and HindⅢ and was identified by the agarose gel electrophoresis and sequence scanning. Then the mB7-H4 corroborated by sequencing was inserted into the fluorescence expression vector MYC-HIS-EGFP-N after cut by the restriction enzymes to construct B7-H4-EGFP and control-EGFP eukaryotic expression vectors. The recombinant plasmids were transfected into JM109 competence bacteria, and were extracted and identified by the agarose gel electrophoresis and the sequencing after cut with the restriction enzymes. They were transfect-ed into CHO cell through lipofectamine? 2000, and the CHO cell lines expressing stably the fusion protein were obtained through G418 selection. MTT colorimetry was used to assess the effect of B7-H4 on the proliferation of lymphocyte in the culture of lymphocyte from BALB/c or C57 mouse respectively and in co-culture of lymphocyte from both BALB/c and C57 mouse. Result The gene sequences of B7-H4 cDNA cloned from mouse and TA-mB7-H4 constructed were correct by sequencing. The transfective CHO cells slahly expressed the recombinant transmembrane B7-H4 protein. The B7-H4 protein suppressed the lymphocyte proliferation either in the culture of lymphocyte respectively and in co-culture of lymphocyte from BALB/c and C57 mouse. Conclusion The B7-H4 eukaryotic expression vector

  16. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

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

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

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

  18. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

    Directory of Open Access Journals (Sweden)

    Finnegan Alison

    2008-02-01

    Full Text Available Abstract Background All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s, particularly T-helper type 1 (Th1 responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs. We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. Methods Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8 were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15 with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49–80. Group 1 subjects' lymphocyte proliferation response to Aluminum+3, Cobalt+2, Chromium+3, Copper+2, Iron+3, Molybdenum+5, Manganeese+2, Nickel+2, Vanadium+3 and Sodium+2 chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl3, 0.1 mM NiCl2, 0.1 mM CoCl2 and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. Results Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p 2 fold stimulation index response, p 10 mM. The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes

  19. Comparing seven mitogens with PHA-M for improved lymphocyte stimulation in dicentric chromosome analysis for biodosimetry.

    Science.gov (United States)

    Beinke, C; Port, M; Lamkowski, A; Abend, M

    2016-02-01

    Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose estimation. Two limiting factors of DCA are the time-consuming lymphocyte stimulation and proliferation using the lectin PHA-M and the upper dose limit of individual dose assessment of ∼4 Gy. By measuring the mitotic index (MI), the authors investigated systematically whether the stimulation of lymphocytes can be improved after administration of alternative (and combined) mitogens. The authors compared the lymphocyte stimulation effectiveness of the traditionally used PHA-M (from Phaseolus vulgaris) with seven cited mitogens by determination of MIs: five lectins namely CNA (concanavalin A), PW (pokeweed), LMA (Maackia amurensis), LTV (T. vulgaris), PHA-L (P. vulgaris) as well as LPS (lipopolysaccharide, Escherichia coli) and SLO (streptolysine O, Streptococcus pyogenes) were applied. The conventional protocol using PHA-M for lymphocyte stimulation proved to be superior over lower/higher PHA-M concentrations as well as seven other mitogens administered either alone or combined with SLO or LPS.

  20. BSAP/Pax-5在B淋巴细胞发育、增殖、分化中的作用%Effect of BSAP/Pax-5 on the Development, Proliferation and Differentiation of B Lymphocyte Cell

    Institute of Scientific and Technical Information of China (English)

    谭余庆; 张永祥

    2001-01-01

    BSAP, a B cell lineage-specific activator protein, is a nucleus transcription factor and is en coded by the Pax-5 gene. It is a critical modulator of B cell development, proliferation and differentia tion. BSAP also influences B cell immunoglobulin secretion at later stages of B cell differentiation.%BSAp,一个B细胞特异性激活蛋白,由Pax-5转录的核蛋白。作为核转录因子,其在B细胞的发育、增殖和分化中起重要作用。同时也影响B细胞分化晚期的Ig的分泌。

  1. Analysis of IL-2-like factor in lymphocyte culture supernatant of olive flounder, Paralichthys oliveaceus

    Institute of Scientific and Technical Information of China (English)

    WU Riqin; ZHANG Peijun; LI Jun; XU Yongli

    2005-01-01

    To study immune mechanism of fish lymphocyte we performed a proliferation assay and ELISA using monoclonal antibody against human IL-2. The result showed that an interleukin-2 (IL-2)-like factor was detected in the supernatant of plant haemoglutinin (PHA)-stimulated lymphocyte culture from peripheral blood,spleen and head kidney of olive flounder, Paralichthys olivaceus. The quantities of IL-2-1ike factor in the supematant from different lymphoid tissues were quite different. The IL-2 like factor in the supernatant from cultured head kidney lymphocytes was much higher than those of peripheral blood lymphocytes and spleen lymphocytes (P<0.01). The IL-2 activity was found in either mouse thymocyte proliferation assay or flounder head kidney lymphocyte proliferation assay and shown to have obvious enhancing effect on proliferation of the above two types of cell. The recombinant human IL-2 (rhIL-2) was able to stimulate flounder thymocyte proliferation and used to detect the IL-2 receptor (IL-2R) on the surface of flounder lymphocyte. The cross-reaction between the lymphocytes of flounder peripheral blood and CD25(IL-2R) was detected with flow cytometry and shown that the percentage of CD25-positive cell in peripheral blood was 7.74± 0.67%.

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

    Science.gov (United States)

    2013-08-20

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

  3. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

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

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

    Science.gov (United States)

    2013-07-01

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

  5. Does programmed CTL proliferation optimize virus control?

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Thomsen, Allan Randrup

    2005-01-01

    CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferati...

  6. Effect of Oxymatrine on CD4+CD25+ regulatory T cells and lymphocyte proliferation%氧化苦参碱对CD4+CD25+调节性T细胞(Tr)和淋巴细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    李建国; 伍斌; 谢红付; 张江林; 易梅; 李吉

    2008-01-01

    目的 通过分析氧化苦参碱(oxymatrine,OMT)各剂量组对小鼠外周血调节性T细胞(regulatory Tcells,Tr细胞)数量的影响,同时检测OMT对刀豆蛋白A(ConA)刺激的小鼠淋巴结T细胞增殖的影响.探讨OMT治疗ACD的免疫学作用机制.以期为临床用OMT治疗变态反应性疾病提供更深入的理论和实验依据.方法 建立DNFB诱发的小鼠ACD模型.以不同荆量的OMT、PBS、氢化可的松(HCT)进行腹腔注射(ip),在实验进程的第1、7、14、21和28天小鼠尾静脉采血,抗-CD3、抗-CD4、抗-CD25单抗进行三色免疫荧光标记,流式细胞术检测各组CD4+CD25+T细胞数量.利用羧基荧光素乙酰乙酸(CFDA-SE)染色,流式细胞术检测OMT对小鼠淋巴结T细胞增殖的影响.实验数据以SPSS 10.0以及CELLQuest软件进行处理.结果 体外实验证明,在500、125和31μg/mL组的OMT对小鼠淋巴结T细胞增殖呈剂量依赖性抑制,而在16、8、4和2μg/mL组的OMT对小鼠淋巴结T细胞增殖起促进作用,但其剂量依赖关系不明显.腹腔注射OMT能明显提高小鼠外周血中CD4+CD25+T细胞的数量,与HCT组比较(P<0.01),与PBS组比较(P<0.01).结论 OMT对小鼠淋巴结T细胞的增殖呈双向作用;腹腔注射OMT能明显提高小鼠外周血中CD4+CD25+T细胞的数量;即OMT对免疫系统的影响呈双向作用,OMT是一种双向免疫调节剂.%[Objective]To analyse Oxymatrine's(OMT)effects on the quantity of mouse's regulatory T cells(Tr cells)in the peripheral blood and mouse lymphocyte proliferation stimulated by con A,probe into the immunological mechanism that OMT treats allergic contact dermatitis(ACD).[Methods]Building up an ACD mouse medel stimulated by Dinitrofluorobenzene(DNFB),taking intraperitoneal injection (IP)by different dosage8 of OMT,PBS and Hydrocortisone(HCT),collecting blood In 1 d,7 d,14d,21 d and 28 d via mouse tail vein,then marking the T cells with anti-CD3,anti-CD4,anti-CD25 three-colored immune fluorescence

  7. Effects of Sargassum polysaccharide on Proliferation and Oxidative Stress of Splenic Lymphocytes in Chicken%马尾藻多糖对鸡脾脏淋巴细胞增殖及氧化应激影响的实验观察

    Institute of Scientific and Technical Information of China (English)

    张玲; 胡庭俊; 陈炳全

    2011-01-01

    The isolation and purification of Sargassum polysaccharides was carried out and the physicochemical property of Sargassum poly-saccharide was analyzed. The effects of S. Polysaccharide on glutathione concentration, nitric oxide production and cell proliferation were investigated in vitro. The results showed that S. Polysaccharide was obtained with a yield of 152.8 g/L (w/w). S. Polysaccharide at concentration of 100, 200 or 400 mg/L could significantly enhance the lymphocyte proliferation (P <0. 05). Hydrogen peroxide at 50 junol/L could induce oxidative stress of splenic lymphocytes in chicken. S. Polysaccharides at 400 mg/L could increase glutathione level significantly when the incubation time were 4 hours or 12 hours (P<0.05) and could decrease the level of nitric oxide in splenic lymphocytes significantly in chicken (P <0.05) at 8 hour. From the findings, it could be concluded that S. Polysaccharides markedly enhance antioxidant activity and may have potential immunomodulatory effect in chicken.%马尾藻具有很高的食用和药用价值,分离提取马尾藻多糖(Sargassum polysaccharides,SP),对其理化性质进行分析;研究马尾藻多糖对氧化应激态鸡脾脏淋巴细胞内谷胱甘肽(GSH)和一氧化氮(NO)分泌水平及淋巴细胞体外增殖的影响.结果表明:马尾藻多糖提取率为152.8 g/L;马尾藻多糖浓度为100、200、400 mg/L时,能显著促进体外培养的鸡脾脏淋巴细胞增殖;H2O2浓度为50 μmol/L时,能诱导体外培养的鸡脾脏淋巴细胞处于氧化应激状态.马尾藻多糖浓度为400 mg/L,与细胞共孵育4h或12h,能显著增加氧化应激态细胞内GSH含量;共孵育培养8h,能显著降低氧化应激态细胞的NO水平.马尾藻多糖能促进鸡脾脏淋巴细胞增殖,并通过调节细胞内GSH和NO水平,提高免疫细胞的抗氧化能力,发挥免疫调节作用.

  8. Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Svenson, M; Theander, T G

    1987-01-01

    Effect of pyrimethamine, an antimalarial antifolate, and of mefloquine, chloroquine, and quinine, which belong to the quinoline group of antimalarials, on proliferation and interleukin 2 (IL-2) production of human lymphocytes was studied in vitro. Pyrimethamine at concentrations above therapeutic...

  9. An intrinsic GABAergic system in human lymphocytes.

    Science.gov (United States)

    Dionisio, Leonardo; José De Rosa, María; Bouzat, Cecilia; Esandi, María Del Carmen

    2011-01-01

    γ-amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central nervous system and it is also present in non-neuronal cells. In this study we investigated the presence of neuronal components of the GABAergic system in lymphocytes and its functional significance. By using RT-PCR we detected mRNA expression of different components of the GABAergic system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters (GAT-1 and GAT-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) subunits that conform ionotropic GABA receptors. The presence of VIAAT protein in resting and activated cells was confirmed by immunocytochemistry. The functionality of GABA transporters was evaluated by measuring the uptake of radioactive GABA. The results show that [(3)H]GABA uptake is 5-fold higher in activated than in resting lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist of ionotropic GABA receptors, elicit macroscopic currents in about 10-15% of the cells. Finally, by using [(3)H]thymidine incorporation assays, we determined that the presence of agonists of GABA receptor during activation inhibits lymphocyte proliferation. Our results reveal that lymphocytes have a functional GABAergic system, similar to the neuronal one, which may operate as a modulator of T-cell activation. Pharmacological modulation of this system may provide new approaches for regulation of T-cell response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Acute Lymphocytic Leukemia

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. The changes of T lymphocytes and cytokines in ICR mice fed with Fe3O4 magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Wang J

    2011-04-01

    Full Text Available Jun Wang1, Baoan Chen1, Nan Jin1, Guohua Xia2, Yue Chen1, Ying Zhou1, Xiaohui Cai1,2, Jiahua Ding1, Xiaomao Li3, Xuemei Wang41Department of Hematology, Zhongda Hospital, 2Department of Medical Laboratory, Medical School, Southeast University, Nanjing, People's Republic of China; 3Department of Physics, University of Saarland, Saarbruecken, Germany; 4National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory, Southeast University, Nanjing, People’s Republic of ChinaAbstract: The aim of this article is to study the changes inhibited T lymphocytes and cytokines related to the cellular immunity in ICR (imprinting control region mice fed with Fe3O4 magnetic nanoparticles (Fe3O4-MNPs. The Fe3O4-MNPs were synthesized, and their characteristics such as particle size, zeta potential, and X-ray diffraction patterns were measured and determined. All ICR mice were sacrificed after being exposed to 0, 300, 600, and 1200 mg/kg of Fe3O4-MNPs by single gastric administration for 14 days. Splenocytes proliferation was indicated with stimulate index by MTT assay; release of cytokines in the serum of ICR mice was detected by enzyme-linked immunosorbent assay, and the phenotypic analyses of T-lymphocyte subsets were performed using flow cytometry. Our results indicated that there were no significant differences in splenocyte proliferation and release of cytokines between exposed and control groups. Furthermore, there was no significant difference in the proportions of T-lymphocyte subsets in the low-dose Fe3O4-MNPs group when compared to the control group, but the proportions of CD3+CD4+ and CD3+CD8+ T-lymphocyte subsets both in the medium- and high-dose Fe3O4-MNPs groups were higher than those in the control group. It is concluded that a high dose of Fe3O4-MNPs, to some extent, could influence in vivo immune function of normal ICR mice.Keywords: Fe3O4, magnetic nanoparticles, splenocyte proliferation, release of cytokines, T-lymphocyte subsets, ICR

  13. Association of the peroxisome proliferator-activated receptor-gamma2 Pro12Ala but not the C1431T gene variants with lower body mass index in Type 2 diabetes.

    Science.gov (United States)

    Mohamed, M Ben Hadj; Mtiraoui, N; Ezzidi, I; Chaieb, M; Mahjoub, T; Almawi, W Y

    2007-12-01

    The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor involved in lipid metabolism, adipocyte differentiation and regulation of insulin sensitivity, and is associated with Type 2 diabetes (T2DM). The association of the C1431T silent mutation and the Pro12Ala missense transversion within the PPARgamma gene with the development of T2DM or obesity has often yielded contradictory results. We examined the association of the PPARgamma Pro12Ala and C1431T gene variants and their haplotypes with the susceptibility to T2DM. This was a retrospective study involving 491 T2DM patients and 400 age- and gender-matched controls. Pro12Ala and C1431T genotyping was done by PCR-RFLP analysis. Comparable frequencies of the mutant 12Ala (0.07 vs 0.08, p=0.216) and 1431T (0.12 vs 0.10, p=0.189) alleles, and Pro12Ala (p=0.218) and C1431T (p=0.421) genotypes were seen between patients and in nondiabetic control subjects. While no difference was noted in the distribution of Pro12Ala- C1431T haplotypes and genotypes between patients and controls, the PPARgamma 12Ala, but not 1431T, allele was significantly associated with lower body mass index (BMI) (Pro12Ala (odds ratio =5.340; 95% confidence interval =1.044-27.311) with normal (BMI<25.0) but not with overweight/obesity among T2DM patients. Despite its association with lower BMI among T2DM patients, the PPARgamma gene does not appear to markedly influence Type 2 diabetes among Tunisian subjects.

  14. Recent advances in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    N Vyas

    2012-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL was largely considered to be a disease of slow progression, standard treatment with Chlorambucil and having almost similar prognosis. With the introduction of molecular methods for understanding the disease pathophysiology in CLL there has been a remarkable change in the approach towards the disease. The variation in B-cell receptor response and immunoglobulin heavy chain variable region (IGHV mutation, genetic aberration and defect in apoptosis and proliferation has had an impact on therapy initiation and prognosis. Early diagnosis of molecular variant is therefore necessary in CLL.

  15. Genotoxic effects of the carbamate insecticide Pirimor-50® in Vicia faba root tip meristems and human lymphocyte culture after direct application and treatment with its metabolic extracts.

    Science.gov (United States)

    Valencia-Quintana, Rafael; Gómez-Arroyo, Sandra; Sánchez-Alarcón, Juana; Milić, Mirta; Olivares, José Luis Gómez; Waliszewski, Stefan M; Cortés-Eslava, Josefina; Villalobos-Pietrini, Rafael; Calderón-Segura, María Elena

    2016-12-01

    The aim of the study was to evaluate genotoxic effects of Pirimor-50®, a pirimicarb-based formulation (50 % active ingredient), in human lymphocyte cultures and Vicia faba root meristems. Furthermore, the objective was to examine a combined influence of insecticide treatment with mammalian microsomal S9 and vegetal S10 metabolic fractions or S10 mix metabolic transformation extracts (after Vicia faba primary roots treatment with Pirimor-50®). We used sister chromatid exchange assay-SCE and measured cell cycle progression and proliferation (proportion of M1-M3 metaphases and replication index ratio-RI). Two processes were used for plant promutagen activation: in vivo activation-Pirimor-50® was applied for 4 h to the plant and then S10 mix was added to lymphocytes; and, in vitro activation-lymphocytes were treated with Pirimor-50® and S10 or S9 for 2 h. Direct treatment induced significantly higher SCE frequencies in meristems at 0.01 mg mL-1. In lymphocytes, significantly higher SCE was at 1 mg mL-1 with decrease in RI and M1-M3 metaphase proportions at 0.5 mg mL-1 and cell division stop at 2.5 mg mL1. S10 mix lymphocyte treatment showed significantly elevated SCE values at 2-2.5 mg mL-1, with cell death at 3 mg mL-1. Lymphocyte treatment with Pirimor-50® together with S9 or S10 showed slightly elevated SCE frequency but had a significant influence on RI decrease, with lowest values in S9 treatment. Since no data are available on the genotoxicity of Pirimor-50®, this study is one of the first to evaluate and compare its direct effect in two bioassays, animal and vegetal, and also the effect of plant and animal metabolism on its genotoxic potential.

  16. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

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

  17. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F.S.; Cantu, A.O.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States)); Cox, A.B.; Salmon, Y.L. (Air Force Armstrong Lab., Brookes AFB, TX (United States))

    1994-10-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 [mu]g/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) that that produced by PHA (M1<0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture. (author).

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

    Science.gov (United States)

    2015-11-10

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

  19. mM-CSF 及其剪切体对淋巴细胞白血病Ramos 细胞增殖的抑制作用%Inhibitory effect of mM-CSF and its spliceosome on proliferation of lymphocytic leukemia cell line Ramos

    Institute of Scientific and Technical Information of China (English)

    马翠花; 种靖慧; 廖金凤; 林永敏; 卫佳; 郑国光

    2015-01-01

    目的:探讨膜结合型巨噬细胞集落刺激因子( mM-CSF)及其剪切体( mM-CSF-Δ)对淋巴细胞白血病Ramos细胞增殖的抑制作用。方法采用Overlap PCR法构建带有mM-CSF的真核表达质粒pTARGET-mM-CSF,再进一步构建胞内区截短30个氨基酸的表达质粒pTARGET-mM-CSF-Δ,并进行PCR及DNA双向测序鉴定。将空载体pTARGET、pTARGET-mM-CSF、pTARGET-mM-CSF-Δ质粒分别转染Ramos细胞,经G418筛选稳定表达细胞株,并用RT-PCR、Western blotting进行鉴定;MTT法检测细胞增殖,流式细胞仪检测细胞周期。结果成功构建了mM-CSF和 mM-CSF-Δ的真核表达载体,获得了稳定转染细胞株 Ramos-V、Ramos-M 和 Ramos-Δ。 Ramos-M、Ramos-Δ、Ramos-V细胞增殖能力的OD值分别为0.413±0.014、0.384±0.019、0.463±0.037,Ramos-M细胞与Ramos-Δ细胞比较,Ramos-M、Ramos-Δ细胞分别与Ramos-V细胞比较,P<0.05或<0.01。 Ramos-M、Ramos-Δ、Ramos-V细胞处于G0/G1期的比例分别为41.54%±1.22%、45.60%±1.09%、39.20%±1.53%,Ramos-M细胞与Ramos-Δ细胞比较, Ramos-M、Ramos-Δ细胞分别与 Ramos-V 细胞比较, P <0.05或<0.01。结论 mM-CSF、mM-CSF-Δ均能抑制淋巴细胞白血病Ramos细胞增殖,且后者抑制作用更强。%Objective To investigate the inhibitory effect of membrane-bound macrophage colony-stimulating factor ( mM-CSF) and its spliceosome ( mM-CSF-Δ) on proliferation of lymphocytic leukemia cell line Ramos.Methods The eukaryotic expression plasmid of pTARGET-mM-CSF with mM-CSF was constructed with Overlap PCR, and then pTAR-GET-mM-CSF-Δof 30 amino acide located in the intracellular region of brachytmema mutation was obtained; and mean-while, they were identified by PCR and DNA sequencing.The empty vector pTARGET, pTARGET-mM-CSF and pTAR-GET-mM-CSF-Δplasmid were transfected into Ramos cells, the cell line with stable expression was screened by G418 and

  20. Inhibition of lipopolysaccharide-induced myeloid-derived suppressor cells in the proliferation of spleen T lymphocytes%脂多糖诱导的CD11b+Gr-1+髓源抑制性细胞对小鼠脾脏T细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    郑燕妮; 于化鹏; 陈新; 邓火金; 樊慧珍; 龚雨新; 刘俊芳

    2012-01-01

    Objective To explore the effects of lipopolysaccharide (LPS)-induced myeloid-derived suppressor cells (MDSCs) on the proliferation of spleen T lymphocytes.Methods BALB/c mice were randomly divided into two groups:LPS group and normal control group.They were injected intraperitoneally with LPS and normal saline solution respectively.MDSCs were separated with CD11b immunomagnetic beads from the spleen extract of mice. The morphological characteristics of MDCSs were observed by Wright-Giemsa staining and the characteristic molecules on cell surface identified by flow cytometry.And the effects of MDSCs on the in vitro proliferation of T cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT).Results The proportion of MDSCs in the spleen of the LPS group was much more than that of the normal control group ( 27.4% ± 6.6% vs 5.1% ± 3.8% ; t =5.06,P =0.007 ).CD11b + Gr-1 +MDSCs could be separated by CD11b immunomagnetic beads from the spleen of mice injected with LPS at a high purity of 84.0% +4.2%.MTT method showed that the proliferation of T cells decreased significantly after a co-cultivation with CD11 b+ M DSCs versus the control group.And it was positively correlated with the number of M DSCs ( F =46.26,P =0.000 ).Conclusions A high purity of LPS-induced myeloid-derived suppressor cells may be separated with CD11 h immunomagnetic beads.And it has dose-dependent inhibitory effects on the proliferation of the spleen T lymphocytes.%目的 观察脂多糖诱导的CD11b+Gr-1+髓源抑制性细胞(MDSCs)对小鼠脾脏T细胞增殖的影响,探讨其在免疫调控可能发挥的作用.方法 10只6~8周龄BALB/c小鼠随机数字表法随机分为脂多糖组和对照组各5只,分别予脂多糖或生理盐水腹腔注射;采用CD11b磁珠从脾脏组织中分选MDSCs,通过瑞氏-姬姆萨染色观察细胞形态,并用流式细胞术检测细胞表面特征分子表达情况;四唑盐(MTT)比色法测定与MDSCs在体外共培养

  1. Beryllium Lymphocyte Proliferation Test Surveillance Identifies Clinically Significant Beryllium Disease

    Science.gov (United States)

    Mroz, Margaret M.; Maier, Lisa A.; Strand, Matthew; Silviera, Lori; Newman, Lee S.

    2011-01-01

    Background Workplace surveillance identifies chronic beryllium disease (CBD) but it remains unknown over what time frame mild CBD will progress to a more severe form. Methods We examined physiology and treatment in 229 beryllium sensitization (BeS) and 171 CBD surveillance-identified cases diagnosed from 1982 to 2002. Never smoking CBD cases (81) were compared to never smoking BeS patients (83) to assess disease progression. We compared CBD machinists to non-machinists to examine effects of exposure. Results At baseline, CBD and BeS cases did not differ significantly in exposure time or physiology. CBD patients were more likely to have machined beryllium. Of CBD cases, 19.3% went on to require oral immunosuppressive therapy. At 30 years from first exposure, measures of gas exchange were significantly worse and total lung capacity was lower for CBD subjects. Machinists had faster disease progression as measured by pulmonary function testing and gas exchange. Conclusions Medical surveillance for CBD identifies individuals at significant risk of disease progression and impairment with sufficient time since first exposure. PMID:19681064

  2. 不同生长阶段猪小肠上皮细胞增生和凋亡指数的变化规律%Variation on enterocyte apoptosis and proliferation index of pigs at different growth phases

    Institute of Scientific and Technical Information of China (English)

    赵元; 秦贵信; 张兵; 王涛; 王波; 孙泽威; 鲍男

    2011-01-01

    选取军牧一号29日龄(7.06±0.18)kg、99日龄(44.54±9.0 4)kg和169日龄(78.93±7.37)kg去势公猪各5头,分别进行仔猪、生长猪和肥育猪3个生理阶段的动物试验。仔猪于28日龄断奶,每一阶段试验期为7d。试验期结束后屠宰,迅速采集十二指肠、空肠中段和回肠组织样品。采用Ki-67抗体或TUNEL免疫组织化学染色方法分别检测小肠上皮细胞增生或凋亡情况,同时测定小肠绒毛高度和隐窝深度。结果表明,随着猪日龄的增长,小肠绒毛高度和隐窝深度增大(P〈0.01);肠上皮细胞凋亡和增生指数逐渐降低(P〈0.001)。无论哪一生长阶段的猪,不同肠段上皮细胞凋亡和增生指数有着相同的变化规律,空肠中段最高,回肠最低(P〈0.01)。%Five weanling(7.06±0.18) kg,5 growing(44.54±9.04) kg,or 5 finishing(78.93±7.37) kg General No.1 barrows,weaned on the 28 days of age,were randomly allotted to three experiments with five replicates for different growth phases,respectively.All the experimental periods were followed for 7 days.The tissue of duodenum,middle jejunum and ileum of pigs at different growth phases were collected,5 μm thick sections of small intestinal tissue were stained with the TUNEL method to assess apoptotic activity,and with Ki-67 immunohistochemistry to assess cellular proliferation.Meanwhile,villus height and crypt depth were determined.The results indicated that with the aging of pigs,the proliferative index and apoptotic index significantly decreased(P〈 0.01),and the villus height and crypt depth increased(P 〈0.01).The apoptotic and proliferative indexes had the same variation for piglets,growers and finishers(P〈0.01),the highest in the mid-jejunum and the lowest in the ileum.

  3. The in vitro genotoxic effects of a commercial formulation of alpha-cypermethrin in human peripheral blood lymphocytes.

    Science.gov (United States)

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2009-01-01

    alpha-Cypermethrin, a highly active pyrethroid insecticide, is effective against a wide range of insects encountered in agriculture and animal husbandry. The potential genotoxicity of a commercial formulation of alpha-cypermethrin (Fastac 100 EC, containing 10% alpha-cypermethrin as the active ingredient) on human peripheral lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus (MN) tests. The human lymphocytes were treated with 5, 10, 15, and 20 microg/ml of alpha-cypermethrin for 24- and 48-hr. alpha-Cypermethrin induced SCEs and CAs significantly at all concentrations and treatment times and MN formation was significantly induced at 5 and 10 microg/ml of alpha-cypermethrin when compared with both the control and solvent control. Binuclear cells could not be detected sufficiently in the highest two concentration of alpha-cypermethrin (15 and 20 microg/ml) for both the 24- and 48-hr treatment times. alpha-Cypermethrin decreased the proliferation index (PI) at three high concentrations (10, 15, and 20 microg/ml) for both treatment periods as compared with the control groups. In addition, alpha-cypermethrin reduced both the mitotic index (MI) and nuclear division index (NDI) significantly at all concentrations for two treatment periods. The PI and MI were reduced by alpha-cypermethrin in a concentration-dependent manner during both treatment times. In general, alpha-cypermethrin showed higher cytotoxic and cytostatic effects than positive control (MMC) at the two highest concentrations for the 24- and 48-hr treatment periods. The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of alpha-cypermethrin in peripheral blood lymphocytes.

  4. LYMPHOCYTE APOPTOSIS IN PSORIASIS

    Directory of Open Access Journals (Sweden)

    О. M. Kapuler

    2006-01-01

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

  5. Preconditioning with basiliximab protects renal ischemia/reperfusion injury by inhibiting T lymphocytes proliferation%巴利昔单抗预处理抑制T淋巴细胞增殖对小鼠肾脏缺血再灌注损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    吕中桥; 范钰; 张艳涛; 邱镇; 胡建鹏; 崔飞伦; 王全兴

    2014-01-01

    vein 30 min before the operation].Then we occluded the renal pedicles on both sides for 45 min.Serum creatinine (Scr),blood urea nitrogen (BUN),fractional excretion of sodium (FENa),renal histology,CD4 + T lymphocytes,CD8 +T lymphocytes,interleukin (IL)-2,tumor necrosis factor (TNF)-α,and IL-6 in blood or the kidney were examined after reperfusion for 1,4,24 h.Results Compared with the Sham group,the levels of Scr [(174.33 ± 7.69),and (51.67 ± 6.56) μmol/L],BUN [(69.90 ± 1.68),and (23.97 ± 2.12) μ mol/L],FENa,the pathological injury scores,IL-2,TNF-α,and IL-6 were increased significantly in IR group and Basiliximab group after reperfusion for 24 h.CD4 + T lymphocytes were also increased in Basiliximab and IR groups after reperfusion for 4 h.All these variables were significantly decreased in Basiliximab group as compared with IR group.Conclusion Preconditioning with basiliximab alleviated renal ischemia/reperfusion injury probably by inhibiting CD4 +T lymphocytes proliferation and decreasing the expression of pro-inflammatory cytokines.

  6. Increased production of interleukin-6 by T lymphocytes from patients with multiple myeloma.

    Science.gov (United States)

    Lapeña, P; Prieto, A; Garcia-Suarez, J; Reyes, E; San Miguel, J; Jorda, J; Alvarez-Mon, M

    1996-01-01

    Alterations in T lymphocyte functions may affect other cellular components of the immune system. Several lymphokines produced by T cells are involved in the proliferation and differentiation of human B lymphocytes. Alterations in the secretion of these molecules may be implicated in the development of B cell lymphoproliferative diseases. We have investigated the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple myeloma (MM) and 16 healthy controls. The phenotypical and functional characteristics of these T lymphocytes were also studied. The proliferative response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in T lymphocytes from MM patients (p 0.05) but not by exogenous IL-6 (p lectin stimulation, the production of IL-2 by T lymphocytes from those patients was normal, while IL-6 secretion was increased.

  7. In-vitro carbofuran induced micronucleus formation in human blood lymphocytes.

    Science.gov (United States)

    Sharma, R K; Rai, D K; Sharma, B

    2012-12-22

    The farmers in general get exposed to different chemicals including pesticides. Many of these compounds are capable of inducing mutations in DNA and lead to several diseases including cancer. Carbofuran is a broad spectrum pesticide and frequently used in agricultural practices in India. In this study we intended to evaluate DNA damage inflicted by pesticide exposure in human blood lymphocytes under in vitro condition. The lymphocytes were exposed to varying concentrations of carbofuran (0—50μM) and analyzed by means of the micronucleus (MN) test. The results obtained showed significant increase in MN frequency after exposure to 5, 10, 25 and 50μM of carbofuran as compared to the control group. The frequencies of MN were observed to be in concentration dependent manner. As we further increase the concentration of carbofuran, we observed significant decrease in the mean percentage of binucleated cells (70—49%) and increase in the number of micronuclei formed per 1000 binucleated cells. Simultaneously, we also observed reduction in Cytokinesis—Block Proliferation index (CBPI) with increase in the carbofuran concentrations. The results indicate that this pesticide may exhibit genotoxic effect at higher concentrations. This study emphasizes the need to reinforce the good practices campaigns in order to enlighten those who work with pesticides and also to make them aware about the importance of using protective measures.

  8. Selective loss of T cell functions in different stages of HIV infection. Early loss of anti-CD3-induced T cell proliferation followed by decreased anti-CD3-induced cytotoxic T lymphocyte generation in AIDS-related complex and AIDS.

    Science.gov (United States)

    Gruters, R A; Terpstra, F G; De Jong, R; Van Noesel, C J; Van Lier, R A; Miedema, F

    1990-05-01

    To investigate the effects of persistant human immunodeficiency virus (HIV) infection on T cell reactivity, functional properties of peripheral blood T cells from HIV-seropositive homosexual men in various stages of infection were studied. T cell activation via CD3 resulting in proliferation and differentiation was measured in a model system independent of accessory cells, using immobilized anti-CD3 monoclonal antibodies (mAb). T cells from HIV-infected asymptomatic men had a decreased proliferative response compared to HIV-negative controls. T cells from AIDS-related complex (ARC) and AIDS patients, compared to T cells from asymptomatic HIV-infected men, had a significantly lower proliferative response to anti-CD3 mAb. This diminished response to anti-CD3 mAb was shown to be due to decreased interleukin (IL) 2 production and could be enhanced by co-stimulation with anti-CD28 mAb or by adding IL 2. Anti-CD3-induced generation of cytotoxic T lymphocytes was fully intact in early infection but was severely decreased in T cells from ARC and AIDS patients. Cytotoxic activity could be restored to near normal levels after co-stimulation with either anti-CD28 mAb or IL 2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL 2 production after stimulation via the CD3/T cell receptor complex. In early HIV infection this seems to be predominantly caused by a specific loss of memory T cells. However, in later stages of infection when both naive and memory T cell subsets are depleted, resulting in a normal naive/memory T cell ratio, T cell functions further deteriorate probably due to intrinsic activation defects. These findings may be of pathogenic relevance since diminished T cell reactivity may facilitate spreading and replication of virulent HIV variants heralding development of ARC and AIDS.

  9. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

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

    2016-01-01

    , and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. DESCRIPTIVE DATA: To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National......, 3,082 patients have been registered. CONCLUSION: The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark......AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  10. Inhibitory effect of arctigenin on lymphocyte activation stimulated with PMA/ionomycin.

    Science.gov (United States)

    Sun, Cheng-Hong; Lai, Xin-Qiang; Zhang, Li; Yao, Jing-Chun; Guan, Yong-Xia; Pan, Li-Hong; Yan, Ying

    2014-04-01

    This study investigated the effect of arctigenin (Arc) on the cell activation, cytokines expression, proliferation, and cell-cycle distribution of mouse T lymphocytes. Mouse lymphocytes were prepared from lymph node and treated with Phorbol-12-myristate-13-acetate (PMA)/Ionimycin (Ion) and/or Arc. CD69, CD25, cytokines, proliferation and cell cycle were assayed by flow cytometry. The results showed that, at concentrations of less than 1.00 micromol x L(-1), Arc expressed non-obvious cell damage to cultured lymphocytes, however, it could significantly down-regulate the expression of CD69 and CD25, as well as TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6 and IL-10 on PMA/Ion stimulated lymphocytes. At the same time, Arc could also inhibit the proliferation of PMA/Ion-activated lymphocytes and exhibited lymphocyte G 0/G1 phase cycle arrest. These results suggest that Arc possesses significant anti-inflammatory effects that may be mediated through the regulation of cell activation, cytokines expression and cell proliferation.

  11. Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

    Science.gov (United States)

    Rithidech, Kanokporn Noy; Tungjai, Montree; Whorton, Elbert B.

    2005-01-01

    The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

  12. Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy.

    Science.gov (United States)

    Fujimura, Masato; Masuda, Kenichi; Hayashiya, Makio; Okayama, Taro

    2011-10-01

    Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (Pfood allergens may be involved in the pathogenesis of canine FA.

  13. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Science.gov (United States)

    2011-01-01

    Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

  14. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

    Science.gov (United States)

    Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

    2011-03-25

    Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  15. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Directory of Open Access Journals (Sweden)

    Chang Shwu-Fen

    2011-03-01

    Full Text Available Abstract Background Arctium lappa (Niubang, a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC, isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2 and interferon-γ (IFN-γ production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  16. D-ribose inhibits DNA repair synthesis in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Zunica, G.; Marini, M.; Brunelli, M.A.; Chiricolo, M.; Franceschi, C.

    1986-07-31

    D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks.

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

    Science.gov (United States)

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

    1985-01-01

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

  18. Automated Scoring and Analysis of Micronucleated Human Lymphocytes.

    Science.gov (United States)

    Callisen, Hannes Heinrich

    Physical and chemical mutagens and carcinogens in our environment produce chromosome abberations in the circulating peripheral blood lymphocytes. The abberations, in turn, give rise to micronuclei when the lymphocytes proliferate in culture. In order to improve the micronucleus assay as a method for screening human populations for chromosome damage, I have (1) developed a high-resolution optical low-light-level micrometry expert system (HOLMES) to digitize and process microscope images of micronuclei in human peripheral blood lymphocytes, (2) defined a protocol of image processing techniques to objectively and uniquely identify and score micronuclei, and (3) analysed digital images of lymphocytes in order to study methods for (a) verifying the identification of suspect micronuclei, (b) classifying proliferating and non-proliferating lymphocytes, and (c) understanding the mechanisms of micronuclei formation and micronuclei fate during cell division. For the purpose of scoring micronuclei, HOLMES promises to (a) improve counting statistics since a greater number of cells can be scored without operator/microscopist fatigue, (b) provide for a more objective and consistent criterion for the identification of micronuclei than the human observer, and (c) yield quantitative information on nuclear and micronuclear characteristics useful in better understanding the micronucleus life cycle. My results on computer aided identification of micronuclei on microscope slides are gratifying. They demonstrate that automation of the micronucleus assay is feasible. Manual verification of HOLMES' results show correct extraction of micronuclei from the scene for 70% of the digitized images and correct identification of the micronuclei for 90% of the extracted objects. Moreover, quantitative analysis on digitized images of lymphocytes using HOLMES has revealed several exciting results: (a) micronuclear DNA content may be estimated from simple area measurements, (b) micronuclei seem to

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

    Science.gov (United States)

    2016-10-04

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

  20. 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.

  1. 术前不同药物干预对人垂体生长激素腺瘤增殖指标数的影响%Effects from preoperative interventions of different drugs on the proliferation indexes of human growth hormone-secreting pituitary adenomas

    Institute of Scientific and Technical Information of China (English)

    徐钰; Michael Buchfelder; 雷霆

    2012-01-01

    Objective To study the influences of different preoperative treatments on proliferation index of somatotrophic adenoma[ monoclonal antibody of cell proliferation associated nuclear antigen ( Mib1 ) and topoisomerase Ⅱ α (Topo Ⅱ α) ] in groups,and to provide instructions for the best treatments.Methods 362 cases of diagnosed acromegaly.Using immunohistochemical staining method to show the positive tumor cells that express Mib-1 and Topo Ⅱα,and comprehensive analysis theLabeling indexs with other clinical data statistically.Result:The Labeling indexes of Mib-1 and Topo Ⅱ α are significantly relative to Hardy classification and invasiveness (all P <0.01 ),only Mib-1 Labeling index correlated the total resection rate significantly (P < 0.01 ).Different preoperative drug interventions have significant effects on the labeling indexes of Mib-1 and Topo Ⅱ α (P <0.01,respectively),and Somatostatin analogue can effectively reduce the tumor proliferation index (P < 0.05).However,Somatostatin analogue contributed not significantly to the tumor proliferation labeling indexes when used along with growth hormone receptor antagonists (P > 0.05).Administer of only dopamine agonists,or together with Sandostatin analogue,and administer of Sandostatin analogues together with growth hormone receptor antagonist showed no significant influences on tumor proliferation index(all P > 0.05).Conclusion The Labeling indexes of Mib-1 and Topo Ⅱ α could be the indicator to estimate invasiveness and prognosis of somatotrophic adenoma.Preoperative administration of Somatostatin analogues help reducing postoperative recurrence and invasiveness of tumor.Growth hormone receptor inhibitors are not suitable for single use but recommended to apply together with Somatostatin analogue.Dopamine agonists are suitable for somatoprolactinomas.%目的 观察术前不同给药对垂体生长激素(GH)腺瘤增殖指标细胞周期相关核抗原Ki-67的抗体(Mib-1)和DNA拓扑异

  2. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

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

  3. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  4. Lymphocytic Interstitial Pneumonia.

    Science.gov (United States)

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

    2016-09-01

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

  5. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  6. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  7. [Proliferative activity parameters and their correlation with genetic damage of blood lymphocytes during cultivation under the conditions of cytokinetic block].

    Science.gov (United States)

    Ingel', F I; Iurchenko, V V; Gus'kov, A S; Krivtsova, E K; Iurtseva, N A

    2006-01-01

    The subjects of the study were 15 volunteers aged 22 to 25 years, who underwent 25 air ionization sessions. The effects of genome instability were evaluated, and correlations between indicators of genome damage (lesions of micronuclei and nucleoplasmatic bridges) and parameters of proliferative and replicative activity (mitotic index, proliferative pool, the fraction of rapidly dividing cells, and replication index) of blood lymphocytes in the culture were studied. In order to establish the associations between the parameters, the parallel cultures were exposed to 0.07 mM of the standard mutagen MNNG during 5 hours. The study showed that the course of air ionization did not induce the micronuclei and nucleoplasmatic bridges in binuclear cells, but increased proliferative cell activity. This effect was accompanied by an increase in the fraction of rapidly dividing cells among all the dividing cells, and an increase in the dispersion of all proliferation parameters. MNNG induced a constant level of micronuclei in binuclear cells during the whole course, but not before the beginning of air ionization. The changes in the parameter "the fraction of dividing cells" (proliferative pool) were the most prominent manifestation of the suppression of proliferation by MNNG. MNNG loading inhibited the formation of binuclear cells most of all. The results demonstrate a non-random character of the correlation between the level of micronuclei in binuclear cells and proliferative activity parameters during cell cultivation under the conditions of cytokinetic block.

  8. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  9. Chronic lymphocytic leukaemia

    Science.gov (United States)

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

    2017-01-01

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

  10. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    Science.gov (United States)

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

    2015-01-01

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

  11. Reduced lymphocyte activation in space - Role of cell-substratum interactions

    Science.gov (United States)

    Gmuender, F. K.; Kiess, M.; Lee, J.; Cogoli, A.; Sonnenfeld, G.

    1992-01-01

    The effect of substratum adhesiveness on lymphocyte responsiveness was investigated by reducing and blocking cell adhesion with poly-HEMA in a simple on ground system. Cells grown on medium thick and thick poly-HEMA films were rounded in shape and displayed no signs of spreading. By contrast, on tissue culture plastic and very thin poly-HEMA films, they showed clear signs of spreading. The mitogenic response of lymphocytes grown on thick poly-HEMA films was reduced by up to 68 percent of the control (tissue culture plastic). Interferon gamma production was virtually nil when the cells were grown on the least adhesive substratum. These results show that activated lymphocytes need to anchor and spread prior to achieving an optimal proliferation response. It is concluded that decreased lymphocyte adhesion could contribute to the depressed in vitro lymphocyte responsiveness found in the microgravity conditions of space flight.

  12. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

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

  13. Virus Location and Lymphocyte Apoptosis in Lymph Nodes of Piglets Infected with PCV-2

    Institute of Scientific and Technical Information of China (English)

    SHI Lü-juan; HAN Hui-li; ZHANG Shu-xia

    2008-01-01

    The present study has been performed to understand the location of the virus, type of apoptotic cells, and their relation to lymph nodes of piglets infected with porcine circovirus type II (PCV-2). Nine 32-day-old conventional piglets free of infection with PCV-2 were used, and distributed into three groups: control group (n=3), piglets inoculated with PCV-2 alone (PCV-2, n = 3), and PCV-2 inoculated and KLH immunostimulated group (PCV-2+KLH, n=3). Superficial inguinal lymph nodes from all piglets were collected for histological examination after 32 days postinoculation, and immunohistochemistry for PCV-2 detection. Location of apoptotic cells was detected with TdT-mediated dUTP nick end labeling (TUNEL) and cell cycle, and the apoptotic rates were measured by flow cytometry. The characteristic histopathological lesions of the piglets in PCV-2 and PCV-2 + KLH were lymphocyte depletions in the cortex and paracortex of the lymph nodes, epithelioid-like macrophage infiltration, and intracytoplasmic inclusion bodies presented in epithelioid-like macrophages. PCV-2 was mainly found in epithelioid-like macrophages by immunohistochemistry. In the lymph nodes, lymphocytes presented higher apoptotic rates in the cortex by TUNEL, special B-cell areas, and similar apoptotic cells were found in this compartment in the control. The apoptotic rates of the lymph nodes were 0.41, 3.34, and 4.88% in the control, PCV-2, and PCV-2 + KLH groups by flow cytometry, respectively. The apoptotic rates of lymph nodes for PCV-2 and PCV-2 + KLH piglets were significantly higher than those for the control group (P<0.05 and P<0.01). The proliferation index (PI) was 0.17±0.01,0.12±0.01 and 0.12±0.04 in the control, PCV-2, and PCV-2 + KLH group, the PI of the control group was higher than that of the other groups, but without the statistical difference. PCV-2 can induce lymphocyte depletion in lymph nodes of piglets by blocking cell proliferation and promoting apoptosis. This is one of the

  14. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes.

    Science.gov (United States)

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2010-04-01

    The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.

  15. Effect of North American ginseng on 137Cs-induced micronuclei in human lymphocytes: a comparison with WR-1065.

    Science.gov (United States)

    Lee, Tung-Kwang; Wang, Weidong; O'Brien, Kevin F; Johnke, Roberta M; Wang, Tao; Allison, Ron R; Diaz, Angelica L

    2008-12-01

    To explore the radioprotective effect of a standardized North American ginseng extract (NAGE) on human peripheral blood lymphocytes (PBL), a micronuclei (MN) assay was conducted in PBL obtained from 12 volunteers. NAGE (50-1000 microg/mL) and WR-1065 (1 mM and 3 mM) were applied to PBL cultures at 0 h and 90 min post-irradiation. It was found that (1) the baseline MN yield of PBL ranged from 14.4 +/- 1.5 to 15.9 +/- 1.5 per 1000 binucleated cells (p > 0.05); after irradiation (1 Gy and 2 Gy), the MN yield increased sharply; (2) MN yields declined with increasing concentrations of NAGE and WR-1065. Even at 90 min post-irradiation of 1 Gy, the maximum level of MN reduction rate caused by NAGE and WR-1065 was 53.8% and 59.2%, respectively; after 2 Gy irradiation, it was 37.3% and 42%, respectively; (3) the MN distribution in PBL followed a non-Poisson distribution in all cases; and (4) both NAGE and WR-1065 showed no significant effect on the proliferation index of lymphocytes. The results indicate that NAGE is a relatively non-toxic natural product, which can be administered as a dietary supplement and has the potential to be a radiation countermeasure. (c) 2008 John Wiley & Sons, Ltd.

  16. Study on psoriatic peripheral blood T-lymphocytes:effects of CD147-targeting small interfering RNA on the expression of CD147 and on cell proliferation and activation%CD147 siRNA转染对银屑病患者外周血T淋巴细胞CD147的表达及细胞增殖、活化的影响

    Institute of Scientific and Technical Information of China (English)

    常静; 陈翔; 粟娟; 匡叶红; 鲁慧; 彭胜

    2008-01-01

    Objective To investigate the effects of small interfering RNA(siRNA)on the expression of CD147 on peripheral blood T-lymphocytes from patients with psoriasis vulgaris,and its effect on the proliferation and activation of these cells.Methods Peripheral blood monouclear cells(PBMC)were obtained from 10 patients with psoriasis vulgaris,and T lymphocytes were isolated.CD147 siRNA was chemically synthesized,then electroporated into the peripheral T-lymphocytes.Untransfected cells,blank-transfected cells and unspecifically transfected cells served as the control.After 24-,48-,72-and 96-hour incubation,RT-PCR was used to detect the mRNA expression of CD147 in these cells.MTT assay and flow cytometry were utilized to assess the proliferation of these cellas,and the expression Of CD25 at 24,48,and 72 hours after the transfection.Results Compared with untransfected cells,the mRNA expression of CD147 declined significantly in CD147 siRNA-transfected cells at 24 hours(P<0.05),reached to the minimum at 48 hours (P<0.01):there was no significant difierence in the expression of CD147 between the two groups of cells at 96 hours after the transfection(P>0.05).There was a decrease of cell proliferation level by(44.5±3.13)%,(50.7±3.5)%and(53.98±4.15)%in CD147 siRNA-transfected cells 24,48 and 72 hours following the transfection,respectively;the corresponding decrease in blank-transfected cells was (37.28±3.56)%,(33.73±3.29)%,and(28.80±1.49)%,respectively,and that in unspecifically transfected cells,(31.29±2.46)%,(36.1±2.62)%and(32.08±2.78)%,respectively.A significant decrease was observed in the proliferation of CD147 siRNA-transfected cells compared with that of blank-transfected cells and unspecifically transfected cells at these three time points(P<0.05,0.01,0.01 respectively).The expression rate of CD25 at 24,48 and 72 hours was(47.23±3.65)%,(31.50±4.22)%and(23.05±4.15)%,respectively,on CD147 siRNA-transfected cells,and,(80.2±4.8)%,(81.6±3.35)%and(83.5±4

  17. In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes.

    Directory of Open Access Journals (Sweden)

    Maciej Guzera

    Full Text Available Mycophenolic acid (MPA is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations- 1 μM (10-3 mol/m3, 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD. The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA] was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance-expansion of Treg cells and lymphocyte apoptosis-was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog.

  18. Testicular Sertoli cells influence the proliferation and immunogenicity of co-cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Ping, E-mail: fanpinggoodluck@163.com [Department of Rheumatism and Immunity, The First Affiliated Hospital Xi' an Jiaotong University School of Medicine, Xi' an, Shaanxi 710061 (China); He, Lan; Pu, Dan; Lv, Xiaohong; Zhou, Wenxu; Sun, Yining; Hu, Nan [Department of Rheumatism and Immunity, The First Affiliated Hospital Xi' an Jiaotong University School of Medicine, Xi' an, Shaanxi 710061 (China)

    2011-01-21

    Research highlights: {yields} The proliferation of dramatic increased by co-cultured with Sertoli cells. {yields} VEGF receptor-2 expression of ECs was up-regulated by co-cultured with Sertoli cells. {yields} The MHC expression of ECs induced by INF-{gamma} and IL-6, IL-8 and sICAM induced by TNF-{alpha} decreased respectively after co-cultured with Sertoli cells. {yields} ECs co-cultured with Sertoli cells also didn't increase the stimulation index of spleen lymphocytes. -- Abstract: The major problem of the application of endothelial cells (ECs) in transplantation is the lack of proliferation and their immunogenicity. In this study, we co-cultured ECs with Sertoli cells to monitor whether Sertoli cells can influence the proliferation and immunogenicity of co-cultured ECs. Sertoli cells were isolated from adult testicular tissue. ECs were divided into the control group and the experimental group, which included three sub-groups co-cultured with 1 x 10{sup 3}, 1 x 10{sup 4} or 1 x 10{sup 5} cell/ml of Sertoli cells. The growth and proliferation of ECs were observed microscopically, and the expression of vascular endothelial growth factor (VEGF) receptor-2 (KDR) was examined by Western blotting. In another experiment, ECs were divided into the control group, the single culture group and the co-culture group with the optimal concentration of Sertoli cells. After INF-{gamma} and TNF-{alpha} were added to the culture medium, MHC II antigen expression was detected by immunofluorescence staining and western blotting; interleukin (IL)-6, IL-8 and soluble intercellular adhesion molecule (sICAM) were measured in the culture medium by ELISA. We demonstrated that 1 x 10{sup 4} cell/ml Sertoli cells promoted the proliferation of co-cultured ECs more dramatically than that in other groups (P < 0.05). Western blotting showed that 1 x 10{sup 4} cell/ml of the Sertoli cells was most effective in the up-regulation of KDR expression in the co-cultured ECs (P < 0.05). Sertoli

  19. 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.

  20. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2007-10-01

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

  1. Kinetics of circulating B lymphocytes in human myeloma

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-04-01

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

  2. Activation of lymphocytes induced by bronchial epithelial cells with prolonged RSV infection.

    Directory of Open Access Journals (Sweden)

    Ling Qin

    Full Text Available Respiratory syncytial virus (RSV preferentially infects airway epithelial cells,which might be responsible for susceptibility to asthma; however, the underlying mechanism is not clear. This study determined the activation of lymphocytes and drift of helper T (Th subsets induced by RSV-infected human bronchial epithelial cells (HBECs in vitro. HBECs had prolonged infection with RSV, and lymphocytes isolated from human peripheral blood were co-cultured with RSV-infected HBECs. Four groups were established, as follows: lymphocytes (group L; lymphocytes infected with RSV (group RL; co-culture of lymphocytes with non-infected HBECs (group HL; and co-culture of lymphocytes with infected HBECs (group HRL. After co-culture with HBECs for 24 hours, lymphocytes were collected and the following were determined in the 4 groups: cell cycle status; apoptosis rate; and concentrations of IL-4, IFN-γ, and IL-17 in the supernatants. Cell cycle analysis for lymphocytes showed a significant increase in S phase cells, a decrease in G1 phase cells, and a higher apoptosis rate in group HRL compared with the other three groups. In group HRL, the levels of IL-4, IFN-γ, and IL-17 in supernatants were also higher than the other three groups. For further study, lymphocytes were individually treated with supernatants from non-infected and RSV-infected HBECs for 24 h. We showed that supernatants from RSV-infected HBECs induced the differentiation of Th2 and Th17 subsets, and suppressed the differentiation of Treg subsets. Our results showed that HBECs with prolonged RSV infection can induce lymphocyte proliferation and apoptosis, and enhance the release of cytokines by lymphocytes. Moreover, subset drift might be caused by RSV-infected HBECs.

  3. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia

    Institute of Scientific and Technical Information of China (English)

    赵霞

    2014-01-01

    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  4. In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Treetip Ratanavalachai

    2008-09-01

    Full Text Available The genotoxic and antigenotoxic effects of Noni fruit juice produced in Thailand have been studied in human lymphocytes for chromosome aberration assay and sister chromatid exchange (SCE assay in vitro. Treatment of Noni fruit juice(3.1-50 mg/ml alone for 3 h did not significantly induce chromosomal aberration or SCE (p<0.05. Noni fruit juice at 6.2 mg/ml is the optimum dose for cell survival and cell replication as demonstrated by the highest value of mitotic index and proliferation index (P.I.. Interestingly, pretreatment of Noni fruit juice at the same concentration of 6.2 mg/ml for 2 hfollowed by mitomycin C treatment at 3 μg/ml for 2 h significantly reduced SCE level induced by mitomycin C (p<0.05. However, these treatments did not show significant decrease in chromatid-type aberrations. Our data indicate that Thai Noni fruit juice is not genotoxic against human lymphocytes in vitro. In addition, pretreatment of Noni fruit juice at 6.2 mg/ml demonstrated no anticlastogenic effect while had some antigenotoxic effects as demonstrated by significant decrease in the SCE level induced by mitomycin C (p<0.05. Therefore, the optimum dose of Noni fruit juice used as a traditional medicine is required and needs to be studied further for the benefit of human health.

  5. Electrostimulation of rat callus cells and human lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aro, H.; Eerola, E.; Aho, A.J.; Penttinen, R.

    1984-01-01

    Asymmetrical pulsing low voltage current was supplied via electrodes to cultured rat fracture callus cells and human peripheral blood lymphocytes. The (/sup 3/H)thymidine incorporation of the callus cells and 5-(/sup 125/I)iodo-2'-deoxyuridine incorporation of the lymphocytes were determined. The growth pattern of callus cells (estimated by cellular density) did not respond to electrical stimulation. However, the uptake of (/sup 3/H)thymidine was increased at the early phase of cell proliferation and inhibited at later phases of proliferation. The (/sup 3/H)thymidine uptake of confluent callus cell cultures did not respond to electrical stimulation. Lymphocytes reacted in a similar way; stimulated cells took up more DNA precursor than control cells at the early phase of stimulation. During cell division, induced by the mitogens phytohemagglutinin and Concanavalin-A, the uptake of DNA precursor by stimulated cells was constantly inhibited. The results suggest that electrical stimuli affect the uptake mechanisms of cell membranes. The duality of the effect seems to be dependent on the cell cycle.

  6. Indexing Images.

    Science.gov (United States)

    Rasmussen, Edie M.

    1997-01-01

    Focuses on access to digital image collections by means of manual and automatic indexing. Contains six sections: (1) Studies of Image Systems and their Use; (2) Approaches to Indexing Images; (3) Image Attributes; (4) Concept-Based Indexing; (5) Content-Based Indexing; and (6) Browsing in Image Retrieval. Contains 105 references. (AEF)

  7. ROLE OF B LYMPHOCYTE AND ITS SUBPOPULATIONS IN PATHOGENESIS OF IMMUNORELATED PANCYTOPENIA

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia (IRP) and explore the action of B lymphocyte in the pathogenic mechanism of IRP.Methods Quantities of whole B lymphocytes and CD5 + B lymphocytes as well as the expressions of Fas and Bcl-2in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission (CR), and 10 normal controls were assayed by flow cytometry.Results The percentages of B lymphocyte and CD5 + B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls ( P < 0. 05 ), and there was no significant difference between the latter two groups (P > 0. 05). There was no significant difference of Fas expression in B lymphocyte among three groups (P >0. 05). The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls (P <0. 01 ), and significantly higher in CR patients than in normal controls (P <0. 01 ). The apoptosisrelated index was significantly lower in untreated patients than in CR patients or normal controls ( P < 0. 05 ), and significantly lower in CR patients than in normal controls ( P < 0. 05 ). The percentage of B lymphocyte was positively correlated with post-treated response time ( r = 0. 53, P < 0. 01 ).Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantities of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.

  8. Resveratrol Alters Proliferative Responses and Apoptosis in Human Activated B Lymphocytes In Vitro

    Science.gov (United States)

    We hypothesized that resveratrol, a polyphenol found in grapes, peanuts, and berries would modulate B lymphocyte proliferation, immunoglobulin synthesis, and apoptosis after activation with T-cell dependent pokeweed mitogen. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of ...

  9. SERUM HAPTOGLOBIN SUPPRESSES T-LYMPHOCYTE FUNCTIONS FOLLOWING BURNS

    Institute of Scientific and Technical Information of China (English)

    王凤君; 黄文华; 黎鳌

    1996-01-01

    It is well known that serum immunosuppressive factors play an important role in the mechanismi of postburn immunosuppression.This study was intended to investigate the effect of haptoglobin,purified from the serum of burned patients by affinity chromatography,on the proliferation and interleukin-2(IL-2)secretion of normal nurine thymocytes induced by conA and the proliferation of IL-2 dependent cell line (CTLL-2) stimulated by recombinant human IL-2,so as to elucidate the role of serum haptoglobin in postburn T-lymphocyte dysfunction.The results showed that purified haptoglobin,at the level equivalent to the concentration found in serum of burned patients,significantly inhibited the prolifration and IL-2 secretion of normal murine thymocytes as well as CTLL-2 proliferation;wheres it exhibited no immunosuppressive effects at the level equivalent to the concentration found in serum of normal vohmteers.According to the results reported here,it is suggested that extraordinary increase in serum haptoglobin level may be an important factor of impaired T-lymphocyte responses following burns.

  10. Potentiation of lymphocyte proliferative responses by nickel sulfide

    Science.gov (United States)

    Jaramillo, A.; Sonnenfeld, G.

    1992-01-01

    Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

  11. Glucose-dependent de Novo Lipogenesis in B Lymphocytes

    Science.gov (United States)

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

    2014-01-01

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

  12. Investigating the in vitro effect of taurine on the infant lymphocytes by sister chromatid exchange.

    Science.gov (United States)

    Ergun, Mehmet Ali; Soysal, Yasemin; Kismet, Erol; Akay, Cemal; Dundaroz, Rusen; Ilhan, Mustafan; Imirzalioglu, Necat

    2006-06-01

    Taurine (2-aminoethane sulphonic acid) is normally present in most mammalian tissues and the most abundant free amino acid in lymphocytes. It participates in various important physiological activities including modulation of the functioning of the central nervous system, cell proliferation, viability and prevention of oxidant-induced injury in many tissues. Its levels in human milk are very high which may be the most important difference from cow's milk. In contrast, an inverse association between breast-feeding and carcinogenesis in childhood or later in life has been suggested by several studies. The study group consisted of eight healthy infants. Peripheral blood was collected and lymphocytes were cultured with either Taurine or Mitomycin C (MMC). Sister chromatid exchange in lymphocytes of the infants were calculated. Statistical differences were found between untreated and MMC-treated lymphocytes, untreated and MMC plus taurine-treated lymphocytes, and between MMC and MMC plus taurine-treated lymphocytes (P = 0.012). The results indicated that taurine plays a protective role in MMC-induced sister chromatid exchange in human lymphocytes. The authors suggest that the high levels of taurine found in human milk may induce protecting effects from breast-feeding against DNA damage and malignancy.

  13. Abnormal lipid rafts related ganglioside expression and signaling in T lymphocytes in immune thrombocytopenia patients.

    Science.gov (United States)

    Zhang, Xian; Zhang, Donglei; Liu, Wenjie; Li, Huiyuan; Fu, Rongfeng; Liu, Xiaofan; Xue, Feng; Yang, Renchi

    2016-01-01

    Aberrant T lymphocytes signaling is considered to play a crucial role in the abnormal immune state of primary immune thrombocytopenia (ITP). Lipid raft has been verified to engage in the T cell receptor (TCR)-mediated T lymphocytes signal transduction. Whether lipid raft-associated T cells signal transduction has impact on the pathogenesis of ITP is still unconfirmed. In this study, we aimed to reveal the abnormality in structure and function of lipid rafts (LRs) in CD4(+) and CD8(+) T lymphocytes of patients with ITP. Our results showed that there was an increased lipid raft aggregation in ITP patients, while this kind of increase would not be influenced by platelet counts or therapeutic regimes. Stimulation by anti-CD3/CD28 monoclonal antibodies promoted enhanced lipid raft clustering in T lymphocytes of ITP patients compared with negative controls. Methyl-β-cyclodextrin (MβCD) could block the abnormal lipid raft aggregation and disrupt the TCR-mediated T cells proliferation and cytokines secretion, including both proinflammatory cytokines and anti-inflammatory cytokines. The spontaneous activation of T lymphocytes from ITP patients might be due to the elevated co-localization of protein tyrosine phosphatase (PTP) CD45 and lipid rafts in patients' CD4(+) and CD8(+) T lymphocytes. These findings suggest that the autoactivation of T lymphocytes from ITP patients may lead to the abnormality in lipid raft structure and raft-anchored proteins, and the changes conversely promote the TCR-mediated T cells activation of ITP patients.

  14. Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced by Mycobacterium bovis BCG▿

    Science.gov (United States)

    Souza, Mariana C.; Penido, Carmen; Costa, Maria F. S.; Henriques, Maria Graças

    2008-01-01

    Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 × 105 bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-γ). Accordingly, in vivo IL-2 or IFN-γ neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ. PMID:18809659

  15. Inhibitory Effects of Berberine on the Activation and Cell Cycle Progression of Human Peripheral Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Lihui Xu; Yi Liu; Xianhui He

    2005-01-01

    The immunosuppressive property of berberine, an isoquinoline alkaloid, has been well documented, but the mechanism of its action on lymphocytes has not been completely elucidated. The present study is to investigate the effect of berberine on the activation and proliferation of lymphocytes, in particular T lymphocytes. Whole peripheral blood from healthy donors was stimulated with phytohemagglutinin (PHA) alone or phorbol dibutyrate (PDB) plus ionomycin, and the expression of CD69 and CD25 on T lymphocytes was evaluated with flow cytometry.The distribution of cell cycles and cell viability were analyzed by staining with propidium iodide (PI) and 7-aminoactinomycin D (7-AAD), respectively. The results showed that 100 μmol/L and 50 μmol/L of berberine significantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA, whereas the effect of 25 μmol/L berberine was not significant. As the incubation time increased, the extent of inhibition decreased.Similarly, the expression of CD25 was also reduced by berberine in a dose-dependent manner over the concentration range of 25-100 μmol/L. Besides, this alkaloid could block lymphocyte cell cycle progression from G0/G1 phase to S and G2/M phase without phase specificity. Moreover, analysis following 7-AAD staining revealed that berberine had no significant cytotoxicity on lymphocytes. Taken together, berberine significantly inhibits the expression of activation antigens on T lymphocytes and also blocks the progression of cell cycles of lymphocytes,suggesting that berberine may exert immunosuppressive effect through inhibiting the activation and proliferation of T cells.

  16. Changes in count and function of splenic lymphocytes from patients with portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Zong-Fang Li; Shu Zhang; Gao-Bo Lv; Ying Huang; Wei Zhang; Song Ren; Jun Yang; Shuang-Suo Dang

    2008-01-01

    AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH.METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function.RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decrease in density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly [(0.822±0.157) × 108 vs (1.174±0.254) × 108, P < 0.01];(3) with the significant increase in the weight of the PH spleen (832.6±278.2 g vs 211.7±85.6 g, P < 0.01),the total quantity of lymphocytes (absolute quantity)increased significantly [(0.685±0.072) × 1011 vs (0.366±0.057) × 1011, P < 0.01]; and (4) the proliferative function of lymphocytes was enhanced: T lymphocytes,(0.022±0.005 vs 0.015±0.003, P < 0.05), and B lymphocytes (0.034±0.006 vs 0.023±0.001, P < 0.01).CONCLUSION: Although lymphocyte density in the spleen decreased in patients with PH, the total quantity of lymphoytes increased because spleen weight increased greatly, along with the proliferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However,complete evaluation of the immune function of the spleenin PH

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

    Directory of Open Access Journals (Sweden)

    Ilaria ePanzeri

    2015-04-01

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

  18. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Liz Carmem Silva-Pereira

    2014-09-01

    Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

  19. Genotoxicity study in lymphocytes of offset printing workers.

    Science.gov (United States)

    Aksoy, Hüseyin; Yilmaz, Serkan; Celik, Mustafa; Yüzbaşioglu, Deniz; Unal, Fatma

    2006-01-01

    The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers.

  20. The Stromal Microenvironment Modulates Mitochondrial Oxidative Phosphorylation in Chronic Lymphocytic Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Hima V. Vangapandu

    2017-10-01

    Full Text Available Peripheral blood chronic lymphocytic leukemia (CLL cells are replicationally quiescent mature B-cells. In short-term cultures, supporting stromal cells provide a survival advantage to CLL cells by inducing transcription and translation without promoting proliferation. We hypothesized that the stromal microenvironment augments malignant B cells' metabolism to enable the cells to cope with their energy demands for transcription and translation. We used extracellular flux analysis to assess the two major energy-generating pathways, mitochondrial oxidative phosphorylation (OxPhos and glycolysis, in primary CLL cells in the presence of three different stromal cell lines. OxPhos, measured as the basal oxygen consumption rate (OCR and maximum respiration capacity, was significantly higher in 28 patients' CLL cells cocultured with bone marrow–derived NK.Tert stromal cells than in CLL cells cultured alone (P = .004 and <.0001, respectively. Similar OCR induction was observed in CLL cells cocultured with M2-10B4 and HS-5 stromal lines. In contrast, heterogeneous changes in the extracellular acidification rate (a measure of glycolysis were observed in CLL cells cocultured with stromal cells. Ingenuity Pathway Analysis of CLL cells' metabolomics profile indicated stroma-mediated stimulation of nucleotide synthesis. Quantitation of ribonucleotide pools showed a significant two-fold increase in CLL cells cocultured with stromal cells, indicating that the stroma may induce CLL cellular bioenergy and the RNA building blocks necessary for the transcriptional requirement of a prosurvival phenotype. The stroma did not impact the proliferation index (Ki-67 staining of CLL cells. Collectively, these data suggest that short-term interaction (≤24 hours with stroma increases OxPhos and bioenergy in replicationally quiescent CLL cells.

  1. 同种异体淋巴细胞与黑素细胞混合培养的实验研究%Allogeneic Mixed Melanocyte-Lymphocyte Culture: An Experimental Study

    Institute of Scientific and Technical Information of China (English)

    项蕾红; 郑志忠; 祝绿川; 廖康煌; 傅雯雯

    2001-01-01

    Objective To investigate the melanocyte-lymphocyte reacion when the allogeneic lymphocytes are cultured with normal melanocytes. Methods 3H - thymidine was incorporated into the mixed culture and the transformation and proliferation rates of lymphocytes were detected by liquid scintillation counting and expressed as cpm. Electron microscopy was used to observe the ultrastructure of melanocytes after mixed culture.Results The results of lymphocyte proliferation were expressed by the stimulation indexes. The stimulation indexes in active vitiligo group was significantly different from that in stable vitiligo group and normal controls. The stimulation indexes of the melanocyte-stimulated group was significantly different from that of ConA-stimulated group. In the mixed melanocyte-lymphocyte reaction, the allogeneic lymphocytes had little effect on the melanocytes. The ultrastructure of the melanocytes in the mixed culture showed normal morphology and normal function of synthesis of melanin. Conclusion As a specific antigen in mixed melanocyte-lymphocyte reaction, melanocyte has a weak effect on the lymphocytes. The melanocytes from stable stage vitiligo patients seem more suitble to be allografted.%目的黑素细胞与同种异体淋巴细胞混合培养,从体外实验来研究排斥反应的可能性。方法采用3H-dTR掺入同位素液态闪烁计数法测定淋巴细胞的转化增殖率,并用透射电镜观察混合培养后黑素细胞的超微结构。结果黑素细胞对同种异体淋巴细胞的转化增殖率与ConA刺激淋巴细胞转化增殖的阳性对照比较,结果显示黑素细胞的促淋巴细胞转化增殖的特异性抗原作用较弱。进一步比较黑素细胞对不同病期白癜风患者淋巴细胞的影响,发现黑素细胞对活动期白癜风患者淋巴细胞的刺激作用相对较强,而稳定期患者和正常人对照组结果差异无显著性。同时电镜观察结果显示同种异体的淋巴细胞对黑

  2. Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases.

    Science.gov (United States)

    Kazama, Itsuro; Tamada, Tsutomu; Tachi, Masahiro

    2015-10-01

    T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes. Patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies further revealed the clinically relevant relationship between the channel expression and the development of chronic respiratory diseases, in which chronic inflammation or the overstimulation of cellular immunity in the airways is responsible for the pathogenesis. In chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive management for the symptoms, the anti-inflammatory effects of macrolide antibiotics were shown to be effective against the over-activation or proliferation of T lymphocytes. Recently, we provided physiological and pharmacological evidence that macrolide antibiotics, together with calcium channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti-inflammatory drugs, effectively suppress the Kv1.3-channel currents in lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In this review article, based on the findings obtained from recent in vivo and in vitro studies, we address the novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory diseases.

  3. REPRESENTATION OF DIFFERENT LYMPHOCYTES' POPULATIONS IN PERIPHERAL BLOOD OF PATIENTS WITH UTERINE MYOMA

    Directory of Open Access Journals (Sweden)

    Ye. E. Zueva

    2014-07-01

    Full Text Available Abstract. Uterine myoma is one of the most widespread gynecological pathology among reproductive women older than 30 years. It is known, that often progress of this pathology is associated with genetic and endocrinologic factors. The immune system is not evident still. The aim of this study was to analyze the state of patient's immune system using flow cytometry assessment of different subpopulations of lymphocytes in peripheral blood. We have examined 46 patients with simple and proliferating forms of the myoma, with different variants of clinical symptoms. Absolute and relative content of different subpopulations of lymphocytes was not differed from normal population's standard. Significant differences of B-lymphocytes and natural killers content were observed between groups with simple and proliferating forms of disease. It was shown that metrorrhagia is associated with high level of T-lymphocytes and T-killers. It was noted that decreasing of B-lymphocytes content took place in cases with large number of uterine nodes. Obtained data are not sufficient for complete understanding of the role of immune system in pathogenesis of this disease, but they confirm that using of immunomodulating therapy is expedient for complex treatment of uterine myoma.

  4. Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barsegian, Vahe; Moeckel, Daniel [Helios Kliniken, Institute of Nuclear Medicine, Schwerin (Germany); Mueller, Stefan P.; Bockisch, Andreas [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Horn, Peter A.; Lindemann, Monika [University Hospital Essen, Institute for Transfusion Medicine, Essen (Germany)

    2017-02-15

    Therapy with the alpha-emitter radium-223 chloride ({sup 223}Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if {sup 223}Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving {sup 223}Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after {sup 223}Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

  5. Emerging roles of L-type voltage gated and other calcium channels in T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Abdallah eBadou

    2013-08-01

    Full Text Available In T lymphocytes, calcium ion controls a variety of biological processes including development, survival, proliferation, and effector functions. These distinct and specific roles are regulated by different calcium signals, which are generated by various plasma membrane calcium channels. The repertoire of calcium-conducting proteins in T lymphocytes includes store-operated CRAC channels, transient receptor potential (TRP channels, P2X channels, and L-type voltage-gated calcium (Cav1 channels. In this paper, we will focus mainly on the role of the Cav1 channels found expressed by T lymphocytes, where these channels appear to operate in a TCR stimulation-dependent and voltage-sensor independent manner. We will review their expression profile at various differentiation stages of CD4 and CD8 T lymphocytes. Then, we will present crucial genetic evidence in favor of a role of these Cav1 channels and related regulatory proteins in both CD4 and CD8 T cell functions such as proliferation, survival, cytokine production and cytolysis. Finally, we will provide evidence and speculate on how these voltage-gated channels might function in the T lymphocyte, a non-excitable cell.

  6. Studies on rabbit lymphocytes in vitro

    Science.gov (United States)

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

    1969-01-01

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

  7. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    Science.gov (United States)

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

    2017-01-01

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

  8. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

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

  9. The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard

    Institute of Scientific and Technical Information of China (English)

    Yi-Zhou Mei; Xiao-Rui Zhang; Ning Jiang; Jun-Ping Cheng; Feng Liu; Pan Zheng; Wen-Xia Zhou; Yong-Xiang Zhang

    2014-01-01

    Background: In clinical studies, the findings on sulfur mustard (SM) toxicity for CD3+CD4+ and CD3+CD8+ T lymphocyte subsets are contradictory. In animal experiments, the effect of SM on the T cell number and proliferation is incompatible and is even the opposite of the results in human studies. In this study, we observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model. Methods: Mice were exposed to SM by subcutaneous injection (20 mg/kg) and were sacrificed 4 h, 24 h, 72 h and 168 h later. Spleen T lymphocyte proliferation was evaluated by3H-TdR. Flow cytometric analysis was used to observe the percentage of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets. The IL-1β, IL-6, IL-10 and TNF-α levels in plasma were assayed using the Luminex method. DNA damage in bone marrow cells was observed with the single cell gel electrophoresis technique (SCGE). Results: SM continuously inhibited the proliferation of lymphocytes for 7 days, and there was a significant rebound of Con A-induced T lymphocyte proliferation only at 24 h. The percentage of CD3+CD4+ and CD3+CD8+ lymphocytes was upregulated, which was accompanied by increased IL-1β and TNF-α and decreased IL-10. The IL-6 level was gradually decreased in the PG group at 4 h. The peak of lymphocytic apoptosis and DNA damage occurred at 24 h and 72 h, respectively. Conclusion: Our results show that SM significantly inhibited T lymphocyte proliferation as well as induced CD3+CD4+ and CD3+CD8+ upregulation. SM intoxication also significantly increased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and inhibited the level of anti-inflammatory cytokine IL-10. Our results may partly be due to the significant SM induced significant apoptosis and necrosis of lymphocytes as well as DNA damage of bone marrow cells. The results provided a favorable evaluation of SM immune toxicity in an animal model.

  10. The azo dyes Disperse Red 1 and Disperse Orange 1 increase the micronuclei frequencies in human lymphocytes and in HepG2 cells.

    Science.gov (United States)

    Chequer, Farah Maria Drumond; Angeli, José Pedro Friedmann; Ferraz, Elisa Raquel Anastácio; Tsuboy, Marcela Stefanini; Marcarini, Juliana Cristina; Mantovani, Mário Sérgio; de Oliveira, Danielle Palma

    2009-05-31

    The use of azo dyes by different industries can cause direct and/or indirect effects on human and environmental health due to the discharge of industrial effluents that contain these toxic compounds. Several studies have demonstrated the genotoxic effects of various azo dyes, but information on the DNA damage caused by Disperse Red 1 and Disperse Orange 1 is unavailable, although these dyes are used in dyeing processes in many countries. The aim of the present study was to evaluate the mutagenic activity of Disperse Red 1 and Disperse Orange 1 using the micronucleus (MN) assay in human lymphocytes and in HepG2 cells. In the lymphocyte assay, it was found that the number of MN induced by the lowest concentration of each dye (0.2 microg/mL) was similar to that of the negative control. At the other concentrations, a dose response MN formation was observed up to 1.0 microg/mL. At higher dose levels, the number of MN decreased. For the HepG2 cells the results were similar. With both dyes a dose dependent increase in the frequency of MN was detected. However for the HepG2, the threshold for this increase was 2.0 microg/mL, while at higher doses a reduction in the MN number was observed. The proliferation index was also calculated in order to evaluate acute toxicity during the test. No differences were detected between the different concentrations tested and the negative control.

  11. AP Index

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Planetary Amplitude index - Bartels 1951. The a-index ranges from 0 to 400 and represents a K-value converted to a linear scale in gammas (nanoTeslas)--a scale that...

  12. Speech Indexing

    NARCIS (Netherlands)

    Ordelman, R.J.F.; Jong, de F.M.G.; Leeuwen, van D.A.; Blanken, H.M.; de Vries, A.P.; Blok, H.E.; Feng, L.

    2007-01-01

    This chapter will focus on the automatic extraction of information from the speech in multimedia documents. This approach is often referred to as speech indexing and it can be regarded as a subfield of audio indexing that also incorporates for example the analysis of music and sounds. If the objecti

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

    Science.gov (United States)

    2017-03-27

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

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

    Science.gov (United States)

    2016-07-18

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

  15. 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.

  16. The Danish National Chronic Lymphocytic Leukemia Registry

    Directory of Open Access Journals (Sweden)

    da Cunha-Bang C

    2016-10-01

    Full Text Available Caspar da Cunha-Bang,1 Christian Hartmann Geisler,2 Lisbeth Enggaard,3 Christian Bjørn Poulsen,4 Peter de Nully Brown,2 Henrik Frederiksen,5 Olav Jonas Bergmann,6 Elisa Jacobsen Pulczynski,7 Robert Schou Pedersen,8 Linda Højberg Nielsen,9 Ilse Christiansen,10 Carsten Utoft Niemann2 1Department of Internal Medicine, Roskilde Hospital, Roskilde, Denmark; 2Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 3Department of Hematology, Herlev Hospital, Herlev, Denmark; 4Department of Hematology, Roskilde Hospital, Roskilde, Denmark; 5Department of Hematology, Odense University Hospital, Odense, Denmark; 6Department of Hematology, Vejle Hospital, Vejle, Denmark; 7Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 8Department of Hematology, Holstebro Hospital, Holstebro, Denmark; 9Department of Hematology, Esbjerg Hospital, Esbjerg, Denmark; 10Department of Hematology, Aalborg University Hospital, Aalborg, Denmark Aim: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL in Denmark. Secondarily, to evaluate adherence to national guidelines and to provide source data for research purposes. Study population: All patients diagnosed with CLL in Denmark from 2008 onward are included in the registry. Patients are followed in one of nine hematology centers. All centers participate in the registry and are all obliged to collect data. Main variables: Predefined data are collected at the time of diagnosis, and follow-up at the time of significant events: treatment, progression, transplantation, and death. Parameters included in the International Workshop on Chronic Lymphocytic Leukaemia criteria for diagnosis, and for decision on treatment initiation as well as characteristics included in the CLL

  17. 2-Methoxyestradiol induce the conversion of human peripheral blood memory B lymphocytes into plasma cells.

    Science.gov (United States)

    Cayer, Marie-Pierre; Drouin, Mathieu; Proulx, Maryse; Jung, Daniel

    2010-04-15

    2-Methoxyestradiol (2ME), an end-metabolite of 17beta-estradiol, is an antiproliferative agent that is currently being tested in clinical trials for cancer treatment. We hereby report that sub-cytotoxic concentrations of 2ME influence the in vitro proliferation of human peripheral blood B lymphocytes. More surprisingly, we have observed that 2ME induces the conversion of CD138(-) B lymphocytes into CD138(+) cells of phenotype similar to immunoglobulin (Ig)-secreting plasma cells. Normal human B lymphocytes expressing CD138 increased in response to 2ME in a dose-dependent fashion, from 2% at baseline up to 31% in cells cultured in the presence of 0.75 microM 2ME. Moreover, most of the converted cells were also CD27(+) and secreted high levels of IgG (151 microg/10(6)cells/24h). IEF studies revealed that conversion occurred in a polyclonal manner. We then exploited this effect of 2ME to gain further insights into the molecular mechanisms that govern changes in transcription factors involved in plasma cells differentiation. Plasma cells generated by 2ME treatment of normal human B lymphocytes expressed elevated levels of IRF4 and reduced levels of Pax5 and Bcl-6. Similarly, levels of XBP-1 and Blimp-1 transcripts were increased. Our results suggest that the differentiation of peripheral blood B lymphocytes into plasma cells requires a similar modulation of transcription factors expression that for tonsil and bone marrow B lymphocytes.

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

    Directory of Open Access Journals (Sweden)

    Jorge Escobar

    2010-01-01

    Full Text Available Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance.

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

    Science.gov (United States)

    Escobar, Jorge; Varela-Nallar, Lorena; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Valdés, Daniel; Aspee, Alexis; Espinosa, Victoria; Rozas, Carlos; Montoya, Margarita; Mandiola, Cristian; Rodríguez, Felipe E.; Acuña-Castillo, Claudio; Escobar, Alejandro; Fernández, Ricardo; Diaz, Hernán; Sandoval, Mario; Imarai, Mónica; Rios, Miguel

    2010-01-01

    Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance. PMID:21253489

  20. Effect of Spleen Lymphocytes on the Splenomegaly in Hepatocellular Carcinoma-bearing Mice

    Institute of Scientific and Technical Information of China (English)

    FANG Jing Jing; ZHU Zhen Yuan; DONG Hui; ZHENG Guo Qiang; TENG An Guo; LIU An Jun

    2014-01-01

    Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of IL-2 were measured, and two-dimensional gel electrophoresis (2-DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3+ T lymphocytes and CD8+ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.

  1. 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.

  2. Trajectory Indexing Using Movement Constraints

    DEFF Research Database (Denmark)

    Pfoser, D.; Jensen, Christian Søndergaard

    2005-01-01

    With the proliferation of mobile computing, the ability to index efficiently the movements of mobile objects becomes important. Objects are typically seen as moving in two-dimensional (x,y) space, which means that their movements across time may be embedded in the three-dimensional (x,y,t) space...... is to reduce movements to occur in one spatial dimension. As a consequence, the movement occurs in two-dimensional (x,t) space. The advantages of considering such lower-dimensional trajectories are that the overall size of the data is reduced and that lower-dimensional data is to be indexed. Since off......-the-shelf database management systems typically do not offer higher-dimensional indexing, this reduction in dimensionality allows us to use existing DBMSes to store and index trajectories. Moreover, we argue that, given the right circumstances, indexing these dimensionality-reduced trajectories can be more efficient...

  3. The toxic effects of melamine on spleen lymphocytes with or without cyanuric acid in mice.

    Science.gov (United States)

    Yin, Rong H; Liu, Jiao; Li, Hua S; Bai, Wen L; Yin, Rong L; Wang, Xin; Wang, Wen C; Liu, Bao S; Han, Xiao H; Han, Jie; He, Jian B; Han, Xiao R

    2014-12-01

    Melamine is an organic nitrogenous compound whose acute toxicity was generally thought to be low in animals. In the present work, we investigated the potential cytotoxic effects of melamine on spleen lymphocytes in mice. In the treated group, morphological changes were observed in cultured lymphocytes in vitro. The co-administration of melamine and cyanuric acid caused a declining tendency in stimulation index of spleen lymphocyte. All treated groups had lower ratios of CD4+/CD8+. Both early apoptotic and late apoptotic/necrotic rates of lymphocyte were significantly higher in the co-administration high groups of melamine and cyanuric acid. Melamine-related toxicity promoted the expression of Bax mRNA, and suppressed the expression of Bcl-2 mRNA in spleen of the treated mice. These results provided useful information for assessing the toxicity of melamine on immune system of mammals, and contributed to the existing toxic profile of melamine.

  4. Studies on poison ivy. In vitro lymphocyte transformation by urushiol-protein conjugates.

    Science.gov (United States)

    Dupuis, G

    1979-12-01

    The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy.

  5. AA Index

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The geomagnetic aa index provides a long climatology of global geomagnetic activity using 2 antipodal observatories at Greenwich and Melbourne- IAGA Bulletin 37,...

  6. Walkability Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Walkabiliy Index dataset characterizes every Census 2010 block group in the U.S. based on its relative walkability. Walkability depends upon characteristics of...

  7. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    sinister image and is today a busi- ness-oriented body whose function is to produce quality industrial solutions and adapt technology, products and...people’s image of the reactor by regular monthly visits." We will soon find out whether they will succeed in this. The reactor is ready for start. JPRS...lymphocytic choriomeningitis 300290500 1.13 Monkey Pox Pathogen 300290500 1.14 White Pox Pathogen 300290500 1.15 Pathogen of Kyasanurskaya [as

  8. Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas.

    Science.gov (United States)

    Tandon, Bevan; Peterson, Loann; Gao, Juehua; Nelson, Beverly; Ma, Shuo; Rosen, Steven; Chen, Yi-Hua

    2011-11-01

    Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So far, the data on LEF1 expression in B-cell lymphomas are limited. This study represents the first attempt to assess LEF1 by immunohistochemistry in a large series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was observed in virtually all neoplastic cells in 92 of 92 (100%) chronic lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with strongest staining in cells with Richter's transformation. LEF1 also highlighted the morphologically inconspicuous small lymphocytic lymphoma component in three composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative. In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%) of cells. Diffuse large B-cell lymphoma, however, demonstrated significant variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases. Our results demonstrate that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a convenient marker for differential diagnosis of small B-cell lymphomas. The expression of β-catenin, the coactivator of LEF1 in WNT signaling, was examined in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44 (88%) showed negative nuclear staining. The findings of universal nuclear overexpression of LEF1 but lack of nuclear β-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic

  9. Causes of upregulation of glycolysis in lymphocytes upon stimulation. A comparison with other cell types.

    Science.gov (United States)

    Stark, Heiko; Fichtner, Maximilian; König, Rainer; Lorkowski, Stefan; Schuster, Stefan

    2015-11-01

    In this review, we revisit the metabolic shift from respiration to glycolysis in lymphocytes upon activation, which is known as the Warburg effect in tumour cells. We compare the situation in lymphocytes with those in several other cell types, such as muscle cells, Kupffer cells, microglia cells, astrocytes, stem cells, tumour cells and various unicellular organisms (e.g. yeasts). We critically discuss and compare several explanations put forward in the literature for the observation that proliferating cells adopt this apparently less efficient pathway: hypoxia, poisoning of competitors by end products, higher ATP production rate, higher precursor supply, regulatory effects, and avoiding harmful effects (e.g. by reactive oxygen species). We conclude that in the case of lymphocytes, increased ATP production rate and precursor supply are the main advantages of upregulating glycolysis.

  10. In vitro effects of Thai medicinal plants on human lymphocyte activity

    Directory of Open Access Journals (Sweden)

    Pranee Chavalittumrong

    2007-03-01

    Full Text Available We assessed the effects of Cleistocalyx nervosum var paniala, Gynostemma pentaphyllum, Gynura procumbens, Houttuynia cordata, Hyptis suaveolens, Portulaca grandiflora, Phytolacca americana and Tradescantia spathacea on lymphocyte proliferation and the effects of C. nervosum, G. pentaphyllum, H. suaveolens and P. grandiflora on natural killer (NK cells activity. All of the extracts significantly stimulated human lymphocyte proliferative responses at various concentrations depending on each extract. The extracts of C. nervosum and H. suaveolens were significantly enhanced NK cells activity while those of G. pentaphyllum and P. grandiflora did not alter NK cells function. Our results suggested that the extracts of those plants have stimulating activity on human lymphocytes and could be clinically useful for modulating immune functions of the body.

  11. Virginia ESI: INDEX (Index Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector polygons representing the boundaries of all hardcopy cartographic products produced as part of the Environmental Sensitivity Index...

  12. Louisiana ESI: INDEX (Index Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector polygons representing the boundaries of all the hardcopy cartographic products produced as part of the Environmental Sensitivity Index...

  13. Maryland ESI: INDEX (Index Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector polygons representing the boundaries of all hardcopy cartographic products produced as part of the Environmental Sensitivity Index...

  14. The effect of ultraviolet radiation on early stages of activation of human lymphocytes: inhibition is independent of effects on DNA

    DEFF Research Database (Denmark)

    Castellanos, G; Owens, T; Rudd, C

    1982-01-01

    Low doses (30-84 ergs/mm2, 1 erg = 10(7) J) of ultraviolet radiation (UV) caused severe inhibition of the proliferation of human lymphocytes in vitro. Greatest inhibition was produced when resting cells were irradiated immediately prior to stimulation with concanavalin A (Con A); this was true...

  15. Effect of Regular Circus Physical Exercises on Lymphocytes in Overweight Children

    Science.gov (United States)

    Momesso dos Santos, Cesar Miguel; Sato, Fábio Takeo; Cury-Boaventura, Maria Fernanda; Guirado-Rodrigues, Silvia Helena; Caçula, Kim Guimaraes; Gonçalves Santos, Cristiane Cassoni; Hatanaka, Elaine; de Oliveira, Heloisa Helena; Santos, Vinicius Coneglian; Murata, Gilson; Borges-Silva, Cristina Neves; Hirabara, Sandro Massao; Pithon-Curi, Tania Cristina; Gorjão, Renata

    2015-01-01

    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. PMID:25826263

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

    Directory of Open Access Journals (Sweden)

    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.

  17. The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity.

    Science.gov (United States)

    Finetti, Francesca; Pellegrini, Michela; Ulivieri, Cristina; Savino, Maria Teresa; Paccagnini, Eugenio; Ginanneschi, Chiara; Lanfrancone, Luisa; Pelicci, Pier Giuseppe; Baldari, Cosima T

    2008-05-15

    The ShcA locus encodes 3 protein isoforms that differ in tissue specificity, subcellular localization, and function. Among these, p66Shc inhibits TCR coupling to the Ras/MAPK pathway and primes T cells to undergo apoptotic death. We have investigated the outcome of p66Shc deficiency on lymphocyte development and homeostasis. We show that p66Shc(-/-) mice develop an age-related lupus-like autoimmune disease characterized by spontaneous peripheral T- and B-cell activation and proliferation, autoantibody production, and immune complex deposition in kidney and skin, resulting in autoimmune glomerulonephritis and alopecia. p66Shc(-/-) lymphocytes display enhanced proliferation in response to antigen receptor engagement in vitro and more robust immune responses both to vaccination and to allergen sensitization in vivo. The data identify p66Shc as a negative regulator of lymphocyte activation and show that loss of this protein results in breaking of immunologic tolerance and development of systemic autoimmunity.

  18. Opinion: Interactions of innate and adaptive lymphocytes

    Science.gov (United States)

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

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

  19. Stochastic model for computer simulation of the number of cancer cells and lymphocytes in homogeneous sections of cancer tumors

    CERN Document Server

    Castellanos-Moreno, Arnulfo; Corella-Madueño, Adalberto; Gutiérrez-López, Sergio; Rosas-Burgos, Rodrigo

    2014-01-01

    We deal with a small enough tumor section to consider it homogeneous, such that populations of lymphocytes and cancer cells are independent of spatial coordinates. A stochastic model based in one step processes is developed to take into account natural birth and death rates. Other rates are also introduced to consider medical treatment: natural birth rate of lymphocytes and cancer cells; induced death rate of cancer cells due to self-competition, and other ones caused by the activated lymphocytes acting on cancer cells. Additionally, a death rate of cancer cells due to induced apoptosis is considered. Weakness due to the advance of sickness is considered by introducing a lymphocytes death rate proportional to proliferation of cancer cells. Simulation is developed considering different combinations of the parameters and its values, so that several strategies are taken into account to study the effect of anti-angiogenic drugs as well the self-competition between cancer cells. Immune response, with the presence ...

  20. Effect of levamisole and methisoprinol on in vitro lymphocyte reactivity in chronically irradiated subjects and patients affected by neoplasias

    Energy Technology Data Exchange (ETDEWEB)

    Campo, M.; Chiavaro, I.; Canfarotta, C.; Stivala, F.; Berrardini, A.

    1982-01-01

    The data of this experiment show that Levamisole moderately stimulates T-lymphocyte proliferation and efficiency in vitro and methisoprinol markedly does so when both drugs act in combination with PHA in subjects with severely impaired cell-mediated responsiveness, whereas they do not exert any effect on lymphocytes in normal subjects. B-lymphocyte in vitro responsiveness does not appear to be affected by the immunomodulators, except for some cases of cancer of the stomach wherein B-lymphocyte responsiveness is stimulated in vitro by Levamisole and more evidently by Methisoprinol. These data support the use of Methisoprinol or Levamisole in therapy, and further investigations regarding the mechanisms whereby they might act and the dose-effect relationship which might show to be important for the type of desired immunomodulation would appear appropriate.

  1. S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Brown, P D; Diamant, Marcus; Jensen, P O

    1999-01-01

    Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential...... of cytostatic chemotherapy in CLL and low grade NHL. Recombinant human (rh) IL-6 might increase the in vivo proliferation rate leading to a higher sensitivity for chemotherapy. We tested this hypothesis by administering rhIL-6 to 9 CLL patients and 3 NHL patients in doses of 2.5 micrograms/kg, 5 micrograms....../kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had...

  2. Sequential Assessment of Cell Cycle S Phase in Flow Cytometry: A Non-Isotopic Method to Measure Lymphocyte Activation In Vitro

    Directory of Open Access Journals (Sweden)

    Ch. Kohler

    1997-01-01

    Full Text Available Lymphocyte multiplication can be induced in vitro by mitogens or specific antigens, and is usually measured using isotopic methods involving tritiated thymidine. Cellular proliferation can also be analyzed by flow cytometry techniques based on cell cycle analysis through the measurement of DNA content. We applied this method to lymphocytes from 113 individuals, to evaluate lymphocyte proliferation after stimulation in vitro by a mitogen (phytohaemagglutinin, PHA or a recall antigen (tetanus toxoid, using a kinetic approach with four points sequential measurements of the S and G2 phases over six days of culture. The proportion of cells in S phase after PHA stimulation was significantly higher than in controls overall and as early as on day three of the culture. Activation with a recall antigen significantly induced increasing S phase cell proportions up to day six. These data suggest that flow cytometric assessment of the S phase could be a useful alternative to isotopic methods measuring lymphocyte reactivity in vitro.

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

    Science.gov (United States)

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

    2009-11-19

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

  4. 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

  5. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Suping Ren

    Full Text Available Progestagen-associated endometrial protein (PAEP is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Santina Bruzzone

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

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

    Directory of Open Access Journals (Sweden)

    Jan E. de Vries

    1998-01-01

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

  9. Evaluation of genotoxic activity of tenofovir disoproxil fumarate in human peripheral lymphocytes

    OpenAIRE

    Kubra Kurt; Lale Donbak; Ahmet Kayraldiz

    2016-01-01

    Purpose: Antiretroviral drugs used in the treatment of HIV (Human Immunodeficiency Virus) iinfection, treat by preventing the proliferation of HIV in human body. People with HIV have to use this drugs for lifelong because of inability of the drugs to eradicate the viruses. In this study, we investigated the in vitro genotoxic activity of tenofovir disoproxil fumarate one of the antiretroviral drugs, in human peripheral lymphocytes. Material and Methods: The cells were treated with four d...

  10. Bursa of Fabricius--mitotic index in the follicles of immunized and non-immunized chicks (Gallus domesticus).

    Science.gov (United States)

    Betti, F; Borella, M I

    1979-01-01

    The mitotic index in the cortical compartment of the follicles of the bursa of Fabricius from chicks immunized with sheep red blood cells (SRBC) is always higher when compaired with non-immunized ones. This mitotic index reachs its maximum 6 days after the SRBC injection, coincident with the highest serum antibody titer. The mitotic activity in the cortex of the follicles of the bursa of Fabricius is always higher than that of the medulla during the postembryonic development of chickens (PROCHAZKA, RODAK, KREJCI 1967). Otherwise it is almost established that the cortex is a zone of continuous lymphocyte proliferation, not occuring the same with the medulla. In addition these bursal histological structures are considered as 2 distinct compartments (GROSSI et al. 1974). The purpose of this paper is to study the response in the mitotic index of the cortical and medullary compartments of the follicles of the bursa of immunized and non-immunized chicks. To correlate possible changes in the mitotic index with circulating antibody levels, the serum antibody titer from the same birds was also recorded.

  11. The Assessment of Cytotoxicity and Genotoxicity of Mirtazapine in Human Blood Lymphocytes Using Micronucleus Test

    Directory of Open Access Journals (Sweden)

    M Norizadeh tazehkand

    2015-02-01

    Results: MN formation was not significantly induced at 24- and 48-h treatment periods when compared with control but Nuclear division index (NDI significantly decreased at all concentrations for two treatment periods. Conclusion: Mirtazapine was not genetoxic but was cytotoxic in human peripheral blood lymphocytes. According to this study mirtazapine has cytotoxic effects on human's cells.

  12. Is there a difference between T- and B-lymphocyte morphology?

    NARCIS (Netherlands)

    Strokotov, D.I.; Yurkin, M.A.; Gilev, K.V.; van Bockstaele, D.R.; Hoekstra, A.G.; Rubtsov, N.B.; Maltsev, V.P.

    2009-01-01

    We characterize T- and B-lymphocytes from several donors, determining cell diameter, ratio of nucleus to cell diameter, and refractive index of the nucleus and cytoplasm for each individual cell. We measure light-scattering profiles with a scanning flow cytometer and invert the signals using a coate

  13. The influence of microcystin-LR on monocytes and lymphocytes of mice

    Institute of Scientific and Technical Information of China (English)

    黄夏宁

    2013-01-01

    Objective To investigate the influence of microcystin-LR (MC-LR) on monocytes and lymphocytes in blood of mice and to find a sensitive index of toxic effects.Methods Specific pathogen free Kunming male mice,aging 1 month-old,were randomly divided into 5 groups by

  14. [Adoptive transfer of T lymphocytes].

    Science.gov (United States)

    Vié, H; Clémenceau, B

    2017-09-01

    Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells. Indeed, the management of patients is made very complex both for medical reasons, because the toxicities associated with these treatments are important, and for technical reasons, because the preparation of T lymphocytes for therapeutic use requires dedicated structures. During this same period, knowledge of the mechanisms of regulation of T lymphocytes and the possibilities offered by synthetic biology and techniques of genome engineering have progressed considerably. Combined, they allow envisaging a true "programming" of the T lymphocytes, intended to improve the efficiency of the treatments and the safety of the patients. Medical and industrial perspectives and the role of these approaches in the arsenal of cancer therapies will depend largely on two conditions: the emergence of a robust demonstration of their effectiveness in solid tumors, and the establishment of an acceptable production and distribution model 1. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Lymphocyte subpopulations in Sheehan's syndrome.

    Science.gov (United States)

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

    2013-06-01

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

  16. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

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

    2009-12-01

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

  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. 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 < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in 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.

  19. INDEXING MECHANISM

    Science.gov (United States)

    Kock, L.J.

    1959-09-22

    A device is presented for loading and unloading fuel elements containing material fissionable by neutrons of thermal energy. The device comprises a combination of mechanical features Including a base, a lever pivotally attached to the base, an Indexing plate on the base parallel to the plane of lever rotation and having a plurality of apertures, the apertures being disposed In rows, each aperture having a keyway, an Index pin movably disposed to the plane of lever rotation and having a plurality of apertures, the apertures being disposed in rows, each aperture having a keyway, an index pin movably disposed on the lever normal to the plane rotation, a key on the pin, a sleeve on the lever spaced from and parallel to the index pin, a pair of pulleys and a cable disposed between them, an open collar rotatably attached to the sleeve and linked to one of the pulleys, a pin extending from the collar, and a bearing movably mounted in the sleeve and having at least two longitudinal grooves in the outside surface.

  20. 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.

  1. The nuclear proliferation; La proliferation nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Gere, F. [Ecole Polytechnique, 91 - Palaiseau (France)

    1995-04-01

    In this book is detailed the beginning of nuclear military power, with the first bomb of Hiroshima, the different ways of getting uranium 235 and plutonium 239, and how the first countries (Usa, Ussr, China, United kingdom, France) got nuclear weapons. Then the most important part is reviewed with the details of non-proliferation treaty and the creation of IAEA to promote civilian nuclear power in the world and to control the use of plutonium and uranium in nuclear power plants. The cases of countries who reached the atom mastery, such Israel, South Africa, Pakistan, Iraq, North Korea, Argentina, Brazil, Iran, Algeria, Taiwan and the reasons which they wanted nuclear weapon for or why they gave up, are exposed.

  2. Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1.

    Science.gov (United States)

    Debacq, Christophe; Héraud, Jean-Michel; Asquith, Becca; Bangham, Charles; Merien, Fabrice; Moules, Vincent; Mortreux, Franck; Wattel, Eric; Burny, Arsène; Kettmann, Richard; Kazanji, Mirdad; Willems, Luc

    2005-11-17

    Understanding cell dynamics in animal models have implications for therapeutic strategies elaborated against leukemia in human. Quantification of the cell turnover in closely related primate systems is particularly important for rare and aggressive forms of human cancers, such as adult T-cell leukemia. For this purpose, we have measured the death and proliferation rates of the CD4+ T lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T-lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys with normal CD4 cell counts. In contrast, a substantial decrease in the proliferation rate of the CD4+ T population was observed in lymphocytic monkeys (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This dynamics significantly differs from the generalized activation of the T-cell turnover induced by other primate lymphotropic viruses like HIV and SIV.

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

    NARCIS (Netherlands)

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

    1973-01-01

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

  4. Astaxanthin, a Carotenoid, Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo.

    Science.gov (United States)

    Lin, Kuan-Hung; Lin, Kao-Chang; Lu, Wan-Jung; Thomas, Philip-Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

    2015-12-29

    Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70-300 nM) did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL)- or concanavalin A (Con A, 10 µg/ mL)-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of splenic lymphocytes (p astaxanthin, alone or with Con A, had no apparent effect on interferon (INF-γ) and interleukin (IL-2) production in primary cultured lymphocytes, it enhanced LPS-induced INF-γ production. In an ex vivo experiment, oral administration of astaxanthin (0.28, 1.4 and 7 mg/kg/day) for 14 days did not cause alterations in the body or spleen weights of mice and also was not toxic to lymphocyte cells derived from the mice. Moreover, treatment with astaxanthin significantly increased LPS-induced lymphocyte proliferation ex vivo but not Con A-stimulated lymphocyte proliferation ex vivo. Enzyme linked immunosorbent assay (ELISA) analysis revealed that administration of astaxanthin significantly enhanced INF-γ production in response to both LPS and Con A stimulation, whereas IL-2 production increased only in response to Con A stimulation. Also, astaxanthin treatment alone significantly increased IL-2 production in lymphocytes derived from mice, but did not significantly change production of INF-γ. These findings suggest that astaxanthin modulates lymphocytic immune responses in vitro, and that it partly exerts its ex vivo immunomodulatory effects by increasing INF-γ and IL-2 production without inducing cytotoxicity.

  5. High endothelial venule-like vessels and lymphocyte recruitment in testicular seminoma.

    Science.gov (United States)

    Sakai, Y; Hoshino, H; Kitazawa, R; Kobayashi, M

    2014-03-01

    Seminoma, the most common testicular malignant neoplasm, originates from germ cells and is characterized by the presence of numerous tumour-infiltrating lymphocytes (TILs). Although it is widely accepted that TILs function in surveillance and cytotoxicity in various tumours including seminoma, detailed mechanisms governing TIL recruitment are not fully understood. It has been shown that high endothelial venule (HEV)-like vessels are induced in inflamed and neoplastic tissues and contribute to lymphocyte recruitment in a manner similar to the way physiological lymphocyte homing occurs in secondary lymphoid organs. Here, we report that HEV-like vessels, which express MECA-79(+) 6-sulfo sialyl Lewis X-capped structures, are induced in TIL aggregates in seminoma, and that such vessels potentially recruit circulating lymphocytes, as an E-selectin•IgM chimera bound these vessels in a calcium-dependent manner. These HEV-like vessels express intercellular adhesion molecule 1 (ICAM-1), but not vascular cell adhesion molecule 1 (VCAM-1) or mucosal addressin cell adhesion molecule 1 (MAdCAM-1), which likely contributes to lymphocyte firm attachment. We also found that the number of T cells attached to the luminal surface of HEV-like vessels was greater than the number of B cells (p seminoma tissues via HEV-like vessels, and that tumour-infiltrating CTLs then undergo proliferation after transmigration through HEV-like vessels in testicular seminoma. © 2014 American Society of Andrology and European Academy of Andrology.

  6. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Science.gov (United States)

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  7. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    James R C Miller

    Full Text Available Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  8. Glutamate decreases the secretion of IL-10 by peripheral blood lymphocytes in persons with autoimmune thyroiditis.

    Science.gov (United States)

    Kvaratskhelia, E; Dabrundashvili, N; Gagua, M; Maisuradze, E; Mikeladze, D

    2008-11-01

    Human T lymphocytes expose ionotropic and metabotropic glutamate receptors, which control immune responses, cell activation, maturation, and death. Several cytokines release during inflammation which identification may have important physiological and clinical implications. Main biological function of IL-10 is limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells. Various inflammatory molecules regulated the secretion of IL-8 and IL-10, but the action of glutamate on the biosynthesis of cytokines is unknown. We have found that in peripheral blood lymphocytes glutamate at the concentrations within normal plasma levels (1 x 10(-5) M), as well as at lower concentration (0.3 x 10(-6) M) changes the secretion of immunosuppressive cytokine IL-10, whereas synthesis of proinflammatory chemokine, IL-8 did not changed significantly. Moreover, our results have shown that peripheral blood lymphocytes from patients with autoimmune thyroiditis release less IL-10 at both concentration of glutamate than peripheral blood lymphocytes from healthy persons. These data suggest that glutamate decrease the secretion of IL-10 by peripheral blood lymphocytes, especially in patients with autoimmune thyroiditis that may be responsible for prolongation of inflammation.

  9. Lack of genotoxic effects (micronucleus induction) in human lymphocytes exposed in vitro to 900 MHz electromagnetic fields.

    Science.gov (United States)

    Zeni, O; Chiavoni, A S; Sannino, A; Antolini, A; Forigo, D; Bersani, F; Scarfì, M R

    2003-08-01

    In the present study, we investigated the induction of genotoxic effects in human peripheral blood lymphocytes after exposure to electromagnetic fields used in mobile communication systems (frequency 900 MHz). For this purpose, the incidence of micronuclei was evaluated by applying the cytokinesis-block micronucleus assay. Cytotoxicity was also investigated using the cytokinesis-block proliferation index. The experiments were performed on peripheral blood from 20 healthy donors, and several conditions were tested by varying the duration of exposure, the specific absorption rate (SAR), and the signal [continuous-wave (CW) or GSM (Global System of Mobile Communication) modulated signal]. The following exposures were carried out: (1) CW intermittent exposure (SAR = 1.6 W/kg) for 6 min followed by a 3-h pause (14 on/off cycles); (2) GSM signal, intermittent exposure as described in (1); (3) GSM signal, intermittent exposure as described in (1) 24 h before stimulation with phytohemagglutinin (8 on/off cycles); (4) GSM signal, intermittent exposure (SAR = 0.2 W/kg) 1 h per day for 3 days. The SARs were estimated numerically. No statistically significant differences were detected in any case in terms of either micronucleus frequency or cell cycle kinetics.

  10. Investigating chromosome damage and gammaH2AX response in human lymphocytes and lymphocyte subsets as potential biomarkers of radiation sensitivity

    Science.gov (United States)

    Beaton, Lindsay A.

    This thesis examines in vitro irradiated blood samples from prostate cancer patients exhibiting late normal tissue damage after receiving radiotherapy, for lymphocyte response. Chromosomal aberrations, translocations and proliferation rate are measured, as well as gammaH2AX response in lymphocytes and lymphocyte subsets. The goal of this thesis is to determine whether the lymphocyte response to in vitro radiation could be used as a marker for radiosensitivity. Patients were selected from a randomized clinical trial evaluating the optimal timing of Dose Escalated Radiation and short course Androgen Deprivation Therapy. Of 438 patients, 3% developed Grade 3 late radiation proctitis and were considered to be radiosensitive. Blood was drawn from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated and were analyzed for dicentric chromosomes, excess fragments and proliferation rates (at 6 Gy), translocations, stable and unstable damage (at 4 Gy), and dose response (up to 10 Gy), along with time response after 2 Gy (0 -- 24 h). Chromosome aberrations, excess fragments per cell, translocations per cell and proliferation rates were analyzed by brightfield and fluorescent microscopy, while the gammaH2AX response in lymphocytes and lymphocyte subsets was analyzed by flow cytometry. Both groups were statistically similar for all endpoints at 0 Gy. At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for three endpoints; the mean number of dicentric chromosomes per cell, the mean number of excess fragments per cell and the proportion of cells in second metaphase. At 4 Gy, there were statistically significant differences between the two cohorts for three endpoints; the mean number of translocations per cell, the mean number of dicentric chromosomes per cell and the mean number of deletions per cell. There were no significant differences between the gammaH2AX

  11. Effect of endogenous catecholamines on apoptosis of Con A-activated lymphocytes of rats.

    Science.gov (United States)

    Jiang, Jian-Lan; Peng, Yu-Ping; Qiu, Yi-Hua; Wang, Jian-Jun

    2007-12-01

    Our previous studies show that lymphocytes express tyrosine hydroxylase (TH) and synthesize catecholamines (CAs) including dopamine, epinephrine and norepinephrine, and that the lymphocytes-derived endogenous CAs affect function of lymphocytes via autocrine/paracrine pathways. Over recent years, induction of apoptosis has been suggested to be a possible mechanism underlying the endogenous CAs-mediated lymphocyte proliferation, differentiation and activation. However, direct effect of the lymphocytes-synthesized CAs on lymphocyte apoptosis is less known. In the present study, TH inhibitor alpha-methyl-p-tyrosine (alpha-MT) and monoamine oxydase inhibitor pargyline were employed to block the synthesis and degradation of CAs in lymphocytes activated by concanavalin A (Con A). Apoptotic cells and apoptosis-related genes and proteins, Bax, Bcl-2, Fas, Fas-Ligand (FasL) and caspase-3, were examined in the lymphocytes treated with alpha-MT or pargyline by means of Annexin V/propidium iodide (PI) staining, real-time PCR and Western blot analyses, respectively. The treatment with alpha-MT of 10(-6) M and 10(-5) M (not 10(-7) M) notably reduced intracellular and supernatant DA, E and NE of the Con A-activated lymphocytes in a dose-dependent manner, and correspondingly, the treatment induced a remarkable decrease of apoptotic lymphocytes but not necrotic cells. The expression of Bax, Fas, FasL and caspase-3 mRNAs and proteins was significantly inhibited in the Con A-activated lymphocytes after the cells were treated with alpha-MT of 10(-6) M and 10(-5) M; but the expression of Bcl-2 mRNA and protein was dramatically increased by the alpha-MT treatment. Contrarily, the treatment with pargyline of 10(-6) M and 10(-5) M (not 10(-7) M) evidently increased the intracellular and supernatant DA, E and NE contents of the Con A-activated lymphocytes in a dose-dependent manner, and meanwhile, it caused a striking increase of apoptotic lymphocytes but not necrotic cells. The expression

  12. Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes

    Directory of Open Access Journals (Sweden)

    Halickman Isaac

    2005-06-01

    Full Text Available Abstract Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF. In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs, which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA. WEB 2170 (10-6 to 10-8 M inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.

  13. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    1 Editorials on Faliero’s Parliamentary Address... Parliamentary Address dence-building measures it would promote in the region to realise the objective of non-proliferation. New Delhi Rejects U.S...takes about 250 tonnes of used at Manuguru in the face of advice from juniors that heavy water to run each nuclear reactor. But during the all but a

  14. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers , books, and periodicals. Items...COMMERCE 8NATIONAL TECHNICAL INFORMATION SERVICE ’TIC Q.,’U ’ SPRINGFIELD, VA. 22161 PROLIFERATION ISSUES JPRS-TND-92-023 CONTENTS 16 July 1992 [This...Experts To Tour Azerbaijan ........................................................................................ 12 To Conduct Biochemical Analysis

  15. Battling Nuclear Proliferation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    As the North Korean and Iranian nuclear issues develop and efforts to resolve them continue, global attention to anti-nuclear proliferation and the work of the International Atomic Energy Agency (IAEA) has become even more intense. Pang Sen, Chairman of

  16. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    competence in handling delicate and agricultral projects, medical research, sterilizing issues. tools, and digging oilfields. Electricity Minister Engineer ...CONTENTS 21 October 1992 [This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear...be built by shipping plutonium through the Strait of Malacca, For- the year 2006 to meet the soaring electricity demand, eign Ministry officials said

  17. The Nightmare of Proliferation

    Institute of Scientific and Technical Information of China (English)

    PANG SEN; ZHOU WENYI

    2010-01-01

    @@ The year 2010 unfolded with conflicting developments in the arena of nuclear non-proliferation. Positive news foreshadowed the resumption of the once "dead" six-party talks regarding hostilities on the Korean Peninsula. On the other hand, the Iranian nuclear issue took a downward turn.

  18. Afghanistan Index

    DEFF Research Database (Denmark)

    Linnet, Poul Martin

    2007-01-01

    The Afghanistan index is a compilation of quantitative and qualitative data on the reconstruction and security effort in Afghanistan. The index aims at providing data for benchmarking of the international performance and thus provides the reader with a quick possibility to retrieve valid...... basis. The data are divided into different indicators such as security, polls, drug, social, economic, refugees etc. This represents a practical division and does not indicate that a picture as to for instance security can be obtained by solely looking at the data under security. In order to obtain...... a more valid picture on security this must incorporate an integrated look on all data meaning that for instance the economic data provides an element as to the whole picture of security....

  19. SUBJECT INDEX

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    2, 4, 6-trinitrobenzenesulphonic acid, zinc sulfate, experimental colitis, 2003328AC133 antigen, hematopoietic stem cells, fetal blood, immunophe-notyping, 2003138ALR2 gene, eNOS gene, PON1 gene, RAGE gene, 2003179 ATN-ISI, prognosis, acute renal failure, acute tubular necrosis-individual severity index, acute physiology and chronic health evaluation, 2003118 Alzheimer disease, interleukin-1 beta, tumor necrosis factor alpha,

  20. Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs.

    Science.gov (United States)

    Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra

    2016-01-01

    Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT

  1. Serotonin transporter in lymphocytes of rats exposed to physical restraint stress.

    Science.gov (United States)

    Medina-Martel, Matilde; Urbina, Mary; Fazzino, Fili; Lima, Lucimey

    2013-01-01

    Glucocorticoids and stress cause transcriptional and functional changes on the serotonin transporter (SERT) in the central nervous system. Stress can produce specific modifications of SERT in lymphocytes, which could be associated with alterations in immune response. The aim of this study was to evaluate the effect of a physical restraint stress protocol on (1) rat lymphocyte proliferation in the presence of the selective serotonin reuptake inhibitor fluoxetine and (2) SERT kinetic parameters, i.e. binding capacity (Bmax), affinity (Kd) and Hill coefficient (nH). Male adult Sprague-Dawley rats were placed in Plexiglass boxes (5 h daily for 5 days), and blood was obtained by cardiac puncture on day 6. Serum corticosterone was quantitated by an immunoenzymatic assay. Lymphocytes were isolated by density gradients and adhesion to plastic, of which there was sufficient material for further experiments, then cultured with or without the mitogen concanavalin A (Con A, 2 μg/ml) and fluoxetine (1-50 μM). Cell proliferation was measured with tetrazolium salts, and [(3)H]paroxetine was used as a SERT-specific ligand for binding assays. Restraint produced a significant increase in serum corticosterone of stressed rats. The proliferative response to Con A was similar in the controls and stressed animals. Fluoxetine reduced cell proliferation with and without Con A. Restraint diminished the inhibitory effect of fluoxetine on proliferation. Restraint also increased Bmax and Kd, but decreased nH. Treatment of rats with actinomycin D, a transcription inhibitor, reduced Bmax in stressed animals. Restraint stress modulated the effect of fluoxetine on cell proliferation, probably through the modification of the presence and the function of SERT. Copyright © 2013 S. Karger AG, Basel.

  2. Interpretation of NCCN Guideline: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017

    Directory of Open Access Journals (Sweden)

    Lei XIA

    2016-12-01

    Full Text Available Chronic lymphocytic leukemia (CLL is a kind of chronic lymphocyte proliferative disease with corresponding clinical symptoms caused by the accumulation of mature B lymphocytes in peripheral blood, bone marrow and lymphatic tissues. In recent years, great achievements have been reached on the basic research, new prognostic markers, diagnostic criteria and therapeutic methods in CLL. This study mainly interpreted the corresponding diagnosis and treatment of CLL in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017.

  3. Genetics Home Reference: bare lymphocyte syndrome type I

    Science.gov (United States)

    ... Home Health Conditions bare lymphocyte syndrome type I bare lymphocyte syndrome type I Enable Javascript to view ... boxes. Download PDF Open All Close All Description Bare lymphocyte syndrome type I (BLS I) is an ...

  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. Activation-induced cell death in B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCγ, Ras, and PI3K, which generally speaking, lead to survival However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

  6. The invasive chytrid fungus of amphibians paralyzes lymphocyte responses.

    Science.gov (United States)

    Fites, J Scott; Ramsey, Jeremy P; Holden, Whitney M; Collier, Sarah P; Sutherland, Danica M; Reinert, Laura K; Gayek, A Sophia; Dermody, Terence S; Aune, Thomas M; Oswald-Richter, Kyra; Rollins-Smith, Louise A

    2013-10-18

    The chytrid fungus, Batrachochytrium dendrobatidis, causes chytridiomycosis and is a major contributor to global amphibian declines. Although amphibians have robust immune defenses, clearance of this pathogen is impaired. Because inhibition of host immunity is a common survival strategy of pathogenic fungi, we hypothesized that B. dendrobatidis evades clearance by inhibiting immune functions. We found that B. dendrobatidis cells and supernatants impaired lymphocyte proliferation and induced apoptosis; however, fungal recognition and phagocytosis by macrophages and neutrophils was not impaired. Fungal inhibitory factors were resistant to heat, acid, and protease. Their production was absent in zoospores and reduced by nikkomycin Z, suggesting that they may be components of the cell wall. Evasion of host immunity may explain why this pathogen has devastated amphibian populations worldwide.

  7. Occult Celiac Disease Associated with Lymphocytic Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    1994-01-01

    Full Text Available A 60-year-old male with dermatitis herpetiformis and a previously treated lymphoma involving an inguinal lymph node developed abnormal liver chemistry tests. Because of intermittent diarrhea, additional studies revealed lymphocytic colitis and occult celiac disease that responded to a gluten-free diet. A liver biopsy done to explore persistently abnormal liver chemistry tests showed a portal tract-centred inflammatory process characterized by biliary ductal proliferation, epithelial lymphocytosis and concentric lamellar fibrosis. Quantitation of immunoglobulins was normal and antimitochondrial antibodies were negative. Retrograde cholangiograms showed radiological features typical of primary sclerosing cholangius. The epithelial lymphocycosis reported in gastric, small and large intestinal mucosa of some patients with celiac disease may also be present in the biliary ductal columnar epithelium. This report provides additional evidence that celiac disease may be a far more extensive pathological process.

  8. Is Low Non-Lethal Concentration of Methylmercury Really Safe? A Report on Genotoxicity with Delayed Cell Proliferation

    Science.gov (United States)

    Crespo-Lopez, María Elena; Costa-Malaquias, Allan; Oliveira, Edivaldo H. C.; Miranda, Moysés S.; Arrifano, Gabriela P. F.; Souza-Monteiro, José R.; Sagica, Fernanda Espirito-Santo; Fontes-Junior, Enéas A.; Maia, Cristiane S. F.; Macchi, Barbarella M.; do Nascimento, José Luiz M.

    2016-01-01

    Human exposure to relatively low levels of methylmercury is worrying, especially in terms of its genotoxicity. It is currently unknown as to whether exposure to low levels of mercury (below established limits) is safe. Genotoxicity was already shown in lymphocytes, but studies with cells of the CNS (as the main target organ) are scarce. Moreover, disturbances in the cell cycle and cellular proliferation have previously been observed in neuronal cells, but no data are presently available for glial cells. Interestingly, cells of glial origin accumulate higher concentrations of methylmercury than those of neuronal origin. Thus, the aim of this work was to analyze the possible genotoxicity and alterations in the cell cycle and cell proliferation of a glioma cell line (C6) exposed to a low, non-lethal and non-apoptotic methylmercury concentration. Biochemical (mitochondrial activity) and morphological (integrity of the membrane) assessments confirmed the absence of cell death after exposure to 3 μM methylmercury for 24 hours. Even without promoting cell death, this treatment significantly increased genotoxicity markers (DNA fragmentation, micronuclei, nucleoplasmic bridges and nuclear buds). Changes in the cell cycle profile (increased mitotic index and cell populations in the S and G2/M phases) were observed, suggesting arrest of the cycle. This delay in the cycle was followed, 24 hours after methylmercury withdrawal, by a decrease number of viable cells, reduced cellular confluence and increased doubling time of the culture. Our work demonstrates that exposure to a low sublethal concentration of MeHg considered relatively safe according to current limits promotes genotoxicity and disturbances in the proliferation of cells of glial origin with sustained consequences after methylmercury withdrawal. This fact becomes especially important, since this cellular type accumulates more methylmercury than neurons and displays a vital role protecting the CNS, especially in

  9. Analysis of Delphinidin and Luteolin Genotoxicity in Human Lymphocyte Culture

    Directory of Open Access Journals (Sweden)

    Jasmin Ezić

    2015-08-01

    Full Text Available Introduction: Bioflavonoids delphinidin (2-(3,4,5-Trihydroxyphenylchromenylium-3,5,7-triol and luteolin (2-(3,4-Dihydroxyphenyl-5,7-dihydroxy-4-chromenone have been recognized as promising antioxidants and anticancer substances. Due to their extensive use, the goal of the research was to determine whether they have any genotoxic potential in vitro.Methods: Analysis of genotoxic potential was performed applying chromosome aberrations test in human lymphocyte culture, as this kind of research was not conducted abundantly for these two bioflavonoids. Delphinidin and luteolin were dissolved in DMSO and added to cultures in final concentrations of 25, 50 and 100 μM.Results: In human lymphocytes cultures Delphinidin induced PCDs in all treatments, potentially affecting the cell cycle and topoisomerase II activity. In concentration of 50 μM luteolin showed strong genotoxic effects and caused significant reduction of cell proliferation.Conclusion: Luteolin exhibited certain genotoxic and cytostatic potential. Delphinidin was not considered genotoxic, however its impact on mitosis, especially topoisomerase II activity, was revealed.

  10. Effects of budlein A on human neutrophils and lymphocytes

    Science.gov (United States)

    KNOB, Carollinie Dias; SILVA, Milena; GASPAROTO, Thaís Helena; OLIVEIRA, Carine Ervolino; AMÔR, Nádia Ghinelli; ARAKAWA, Nilton Syogo; COSTA, Fernando Batista; CAMPANELLI, Ana Paula

    2016-01-01

    ABSTRACT Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases and other ailments. Objective In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. Material and Methods Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. Results Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death. Conclusions Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells. PMID:27383709

  11. Indexing of Network-Constrained Moving Objects

    DEFF Research Database (Denmark)

    Pfoser, Dieter; Jensen, Christian Søndergaard

    2003-01-01

    With the proliferation of mobile computing, the ability to index efficiently the movements of mobile objects becomes important. Objects are typically seen as moving in two-dimensional (x,y) space, which means that their movements across time may be embedded in the three-dimensional (x,y,t) space...... management systems typically do not offer higher-dimensional indexing, this reduction in dimensionality allows us to use such DBM- Ses to store and index trajectories. Moreover, we argue that, given the right circumstances, indexing these dimensionality-reduced trajectories can be more efficient than using...

  12. SPONTANEOUS IMMUNOGLOBULIN-SYNTHESIZING ACTIVITY OF B LYMPHOCYTES IN INFLAMMATORY RHEUMATIC DISEASES

    Directory of Open Access Journals (Sweden)

    A.T. T. Mamasaidov

    2007-01-01

    Full Text Available Abstract. The aim of present work was to evaluate clinical significance of B-lymphocytes spontaneous antibody-synthesizing activity by B-lymphocytes (LASA in patients with rheumatic inflammatory diseases (RD, i.e., reactive arthritis (ReA, ankylosing spondylitis (AS, rheumatoid arthritis (RA, and systemic lupus erythematosus (SLE. Significantly higher LASA levels were revealed in the patients with ReA, AS, RA, and SLE, as compared with healthy persons and patients with osteoarthrosis. Clinical significance of LASA indexes and their changes may reflect manifestation and degree of immunological activities in ReA, AS, RA, and SLE.

  13. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

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

  14. Evaluation of the Cell Proliferation Process of Ovarian Follicles in Hypothyroid Rats by Proliferation Cell Nuclear Antigen Immunohistochemical Technique

    Directory of Open Access Journals (Sweden)

    M. Moghaddam Dorafshani

    2012-10-01

    Full Text Available Introduction & Objective: The normal females reproductive function , needs hypothalamus-hypophysis-ovarian extensive hormonal messages. Primary hypothyroidism is characterized by reduced production and secretion of thyroid hormones. During follicular growth PCNA (Proliferating Cell Nuclear Antigen and cycklin D complex play an important role in regulating cell proliferation .This study aimed to determine the cell proliferation index and how this process changes induced by thyroid hormone decreased in rat ovarian follicles.Materials & Methods: In this experimental study, 20 Wistar female rats were divided into experimental and control groups. Experimental group was chemically thyroidectomized by administering propylthiouracil (PTU (500 mg per liter of drinking water. The control group received normal drinking water. After three weeks rats were killed and their ovaries dissected and fixed for the histological preparation. Cell proliferation was determined by PCNA and stereological methods were used for counting cells.Results: Cell proliferation index showed a significant decrease in the frequency of follicular growth from prenatal to graafian follicles in hypothyroidism groups(P0.05 . PCNA expression determined that Primary follicle growth begins earlier. Positive PCNA cells were not observed in primordial follicles of the groups.Conclusion: According to the results of our study, this hypothesis is raised that granulosa cells in growing follicles may be increased by follicle adjacent cells in ovarian stroma . Hormonal changes following the reduction of thyroid hormones may greatly affect the cell proliferation index and lead to faster follicle degeneration.(Sci J Hamadan Univ Med Sci 2012; 19 (3:5-15

  15. Proliferation in cycle

    Energy Technology Data Exchange (ETDEWEB)

    Piao Yunsong [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: yspiao@gucas.ac.cn

    2009-06-15

    In the contracting phase with w{approx_equal}0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w{approx_equal}0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

  16. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    TECHNICAL INFORMATION SERVICE SPRINGFIELD, VA 22161 PROLIFERATION ISSUES JPRS-TND-93-011 CONTENTS 23 April 1993 [This report contains foreign media ...likely after the U.N. Security [Text] Pyongyang, April 17 (KCNA)-Mass media of the Council adopts its first resolution against Pyongyang United States...his interview to the ARGUMENTY I FAKTY upon the path of confrontation and violence . We do not weekly President Leonid Kravchuk dismissed reports want

  17. Study of response of thymic and submaxillary lymph node lymphocytes to administration of lead by different routes.

    Science.gov (United States)

    Teijón, César; Blanco, María Dolores; Romero, Carlos Santiago; Beneit, Juan Vicente; Villarino, Antonio Luis; Guerrero, Sandra; Olmo, Rosa

    2010-06-01

    A number of studies have reported that heavy metals are not only toxic for the organism but they may modulate immune responses. In the current study, the effect of 4-week administration of 200 ppm of PbAc(2), using different routes of administration (orally and intraperitoneal injection), on lymphatic organs was evaluated. In the thymus, the number of lymphocyte cells and the cellularity diminished significantly for both routes of treatment. Regarding the submaxillary lymph nodes, no significant variations took place. Cell-mediated immune response is commonly evaluated by cell proliferation assays. Mitogens are known to induce a vigorous proliferative response in lymphoid cells from mammals. An increase in the proliferation of T lymphocytes stimulated by concanavalin A and the proliferation of B lymphocytes stimulated with lipopolysaccharides was found in thymus for both routes of administration, whereas in the lymph nodes, there was a decrease in proliferation of T lymphocytes. Furthermore, lead administration by intraperitoneal route caused an effect on B and T lymphocyte subpopulations. Thus, there was an increase in B+ cells and a decrease in T+ cells. Regarding CD4+ and CD8+ T cells, there were only variations, concretely a drop in both subpopulations, in lymph nodes when lead was administered intraperitoneally. It is important to emphasize that an increase in apoptosis was found in this tissue. At the histological level, evident alterations were described in thymus both for the oral and for the intraperitoneal route. Therefore, it is possible to show that lead administered by both routes generated effects on an immunological level.

  18. Multiple in vitro and in vivo regulatory effects of budesonide in CD4+ T lymphocyte subpopulations of allergic asthmatics.

    Directory of Open Access Journals (Sweden)

    Elisabetta Pace

    Full Text Available BACKGROUND: Increased activation and increased survival of T lymphocytes characterise bronchial asthma. OBJECTIVES: In this study the effect of budesonide on T cell survival, on inducible co-stimulator T cells (ICOS, on Foxp3 and on IL-10 molecules in T lymphocyte sub-populations was assessed. METHODS: Cell survival (by annexin V binding and ICOS in total lymphocytes, in CD4+/CD25+ and in CD4+/CD25- and Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25-cells was evaluated, by cytofluorimetric analysis, in mild intermittent asthmatics (n = 19 and in controls (n = 15. Allergen induced T lymphocyte proliferation and the in vivo effects of budesonide in mild persistent asthmatics (n = 6 were also explored. RESULTS: Foxp3 was reduced in CD4+/CD25- and in CD4+/CD25+ cells and ICOS was reduced in CD4+/CD25+ cells but it was increased in CD4+CD25-in asthmatics when compared to controls. In asthmatics, in vitro, budesonide was able to: 1 increase annexin V binding and to reduce ICOS in total lymphocytes; 2 increase annexin V binding and Foxp3 and to reduce ICOS in CD4+/CD25- cells; 3 reduce annexin V binding and to increase IL-10 and ICOS in CD4+/CD25+ cells; 4 reduce cell allergen induced proliferation. In vivo, budesonide increased ICOS in CD4+/CD25+ while it increased Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25- cells. CONCLUSIONS: Budesonide modulates T cell survival, ICOS, Foxp3 and IL-10 molecules differently in T lymphocyte sub-populations. The findings provided shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation.

  19. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  20. [Evolution and phylogeny of B lymphocytes].

    Science.gov (United States)

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

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

  1. Assessment of genotoxicity of Lannate-90® and its plant and animal metabolites in human lymphocyte cultures.

    Science.gov (United States)

    Valencia-Quintana, Rafael; Gómez-Arroyo, Sandra; Sánchez-Alarcón, Juana; Milić, Mirta; Olivares, José Luis Gómez; Waliszewski, Stefan M; Cortés-Eslava, Josefina; Villalobos-Pietrini, Rafael; Calderón-Segura, María Elena

    2016-06-01

    This study evaluated direct and metabolic genotoxic effects caused by Lannate-90®, a methomyl-based formulation (90 % active ingredient), in human lymphocyte cultures using sister chromatid exchange assay (SCE). Two processes were used for the plant promutagens evaluation: in vivo activation, applying the insecticide systemically in plants for 4 h and subsequently adding plant metabolites containing extracts to lymphocyte cultures; and in vitro activation, where the insecticide was incubated with Vicia faba S10 mix plus human lymphocyte culture. Direct treatment with the insecticide significantly increased SCE frequency in human lymphocytes (250-750 mgL-1), with cellular death observed at 1000 mgL-1 concentration. Using the extracts of Vicia faba treated with Lannate-90® to treat human lymphocytes, a dose-response relationship was observed. In lymphocyte cultures treated directly with the insecticide for 2 h, a negative response was obtained. When S10 mix was added, SCE frequency did not change significantly. Meanwhile, a mixture of S9 mammalian metabolic mix and Lannate-90® increased the SCE frequency, with an observed concentration-dependent response. Although Lannate-90® induced cellular death at the highest concentrations, it did not cause a delay in cell proliferation in any of the treatments, confirming its genotoxic action. This study is one of the first to evaluate and compare the direct effect of Lannate-90® in two bioassays, animal and vegetal, and the effect of plant and animal metabolism on its genotoxic potential.

  2. Metabolism of peripheral lymphocytes, interleukin-2-activated lymphocytes and tumor-infiltrating lymphocytes from sup 31 P NMR studies

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, O.; Cohen, J.S.; Aebersold, P.

    1989-11-20

    {sup 31}O NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly diefferent form those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase in ATP levels. In all lumphocytes the phosphomonoester (PME) region is dominated by phosphoethanolamine (PE), while there is an unusual absence of phosphocholine (PC). Perfusion of these cells with high concentrations of choline caused only a minimal increase in PC, indicating that choline kinase is not the rate limiting step of lecithin synthesis in lymphocytes. (author). 13 refs.; 3 figs.; 1 tab.

  3. Is there a difference between T- and B-lymphocyte morphology?

    Science.gov (United States)

    Strokotov, Dmitry I; Yurkin, Maxim A; Gilev, Konstantin V; van Bockstaele, Dirk R; Hoekstra, Alfons G; Rubtsov, Nikolay B; Maltsev, Valeri P

    2009-01-01

    We characterize T- and B-lymphocytes from several donors, determining cell diameter, ratio of nucleus to cell diameter, and refractive index of the nucleus and cytoplasm for each individual cell. We measure light-scattering profiles with a scanning flow cytometer and invert the signals using a coated sphere as an optical model of the cell and by relying on a global optimization technique. The main difference in morphology of T- and B-lymphocytes is found to be the larger mean diameters of the latter. However, the difference is smaller than the natural biological variability of a single cell. We propose nuclear inhomogeneity as a possible reason for the deviation of measured light-scattering profiles from real lymphocytes from those obtained from the coated sphere model.

  4. Genotoxicity and cytotoxicity of copper oxychloride in cultured human lymphocytes using cytogenetic and molecular tests.

    Science.gov (United States)

    Bayram, Suleyman; Genc, Ahmet; Buyukleyla, Mehmet; Rencuzogullari, Eyyup

    2016-10-01

    The genotoxicity of copper oxychloride was investigated in human lymphocytes using chromosome aberration (CA) and micronucleus (MN) tests and the randomly amplified polymorphic DNA-polymerase chain reaction technique. The lymphocytes were treated with 3, 6, and 12 µg/mL of copper oxychloride for 24 and 48 h. Copper oxychloride increased CA and abnormal cells in a dose-dependent manner. The frequency of MN and micronucleated binuclear cells also increased at all concentrations and treatment periods. However, copper oxychloride cytotoxicity, observed through lower mitotic and nuclear division index, was significantly lower only at the higher concentrations (6 and 12 µg/mL). Copper oxychloride increased the polymorphic bands and decreased genomic template stability. In conclusion, in this study it was confirmed that copper oxychloride has genotoxic potential for human lymphocytes in vitro. Additionally, caution is advised for its use as a fungicide, because it may increase the risk of exposure through the food chain.

  5. Proliferation of CD8-positive T cells in blood vessels of rat renal allografts.

    Science.gov (United States)

    Grau, V; Fuchs-Moll, G; Wilker, S; Weimer, R; Padberg, W

    2011-09-01

    It is still disputed in which anatomical compartments of allograft recipients T-cells proliferate. After experimental renal transplantation, host monocytes and lymphocytes accumulate in the lumina of graft blood vessels. In this study, we test the hypothesis that T lymphocytes proliferate in the vascular bed of the graft. Kidneys were transplanted in the Dark Agouti to Lewis rat strain combination, an established experimental model for acute rejection. Isogeneic transplantation was performed as a control. Cells in the S-phase of mitosis were detected in situ three days posttransplantation by pulse-labeling with BrdU and by immunohistochemical detection of the proliferating cell nuclear antigen (PCNA). More than 20% of all T-cells in the lumina of allograft blood vessels incorporated BrdU and approximately 30% of them expressed PCNA. In the blood vessels of isografts as well as in other organs of allograft recipients, only few BrdU(+) cells were detected. A majority of the BrdU(+) cells in graft blood vessels expressed CD8. In conclusion, we demonstrate that CD8(+) T lymphocytes proliferate in the lumina of the blood vessels of renal allografts during the onset of acute rejection.

  6. Seasonal changes in haematology, lymphocyte transferrin receptors and intracellular iron in Ironman triathletes and untrained men.

    Science.gov (United States)

    Broadbent, Suzanne

    2011-01-01

    We investigated whether 12 months of chronic endurance training would affect haematology, CD4(+) lymphocyte transferrin receptor (CD71) expression, CD4(+) intracellular iron and the incidence of upper respiratory tract illnesses (URTI) in Ironman triathletes compared with untrained men. Resting venous blood samples were taken from 15 Ironman triathletes (TR 30 ± 5 year) and 12 untrained men (UT 30 ± 6 year) every 4 weeks for 12 months. Erythrocyte, leukocyte and platelet concentration, haematocrit, haemoglobin (Hb) and mean corpuscular haemoglobin (MCHC) were measured with a full blood count. CD4(+) lymphocytes were analysed for changes in transferrin receptor (CD71) expression (CD4(+)CD71(+)), and intracellular iron (Fe(3+)), by flow cytometry. The TR group had significantly lower Hb, MCHC, and platelets for 10, 9 and 11 months, respectively; lower CD4(+)CD71(+) (3 months) and Fe(3+) (1 month), respectively; higher CD4(+)CD71(+) (1 month); a higher lymphocyte count for 4 months. There were no between-group differences in other variables. In both groups haematology and lymphocytes increased during spring, early summer and winter and decreased during late summer/late winter, with an inverse relationship between CD4(+)CD71(+) and Fe(3+). The TR group reported significantly fewer URTI than the UT. Low Hb and MCHC suggest an iron deficiency which may affect triathlete performance. Monthly changes in lymphocytes, CD4(+)CD71(+) and Fe(3+) suggested that spring, summer and late autumn are associated with CD4(+) proliferation. There may be seasonal relationships between haematology and lymphocyte function, independent of endurance training, possibly affecting performance but not the incidence of URTI.

  7. Immunotoxicity of bisphenol A to Carassius auratus lymphocytes and macrophages following in vitro exposure

    Institute of Scientific and Technical Information of China (English)

    YIN Da-qiang; HU Shuang-qing; GU Ying; WEI Li; LIU Shu-shen; ZHANG Ai-qian

    2007-01-01

    Bisphenol A (BPA) is the monomer component of polycarbonate plastics and classified as an endocrine disrupting chemical (EDC).The reproductive toxicity of BPA has been extensively studied in mammals; however, relatively little information is available on the immunotoxic responses of fish to BPA. In this study, we investigated the effects of BPA on the immune functions of lymphocytes and macrophages in Carassius auratus. The effects of BPA were compared with those of two natural steroid hormones, estradiol and hydrocortisone. Proliferation of the two types of cells in response to PHA was measured using colorimetric MTT assay. Macrophage respiratory burst stimulated by Con A was measured using chemiluminescence assay. Results showed that BPA (0.054-5.4 mg/L),estradiol (0.0002-2.0 mg/L) and hydrocortisone (5-50 mg/L) significantly induced Carassius auratus lymphocyte proliferation while higher doses of hydrocortisone (500-5000 mg/L) appeared to be inhibitory. BPA (0.005-50 mg/L), estradiol (0.005-800 mg/L) and hydrocortisone (0.005-500 mg/L) markedly enhanced macrophage proliferation, whereas higher doses of BPA (500-1000 mg/L)appeared to inhibit cell proliferation. Furthermore, higher dosage of BPA (50 mg/L) and hydrocortisone (50 and 500 mg/L) suppressed the macrophages respiratory burst while estradiol is stimulative all the doses tested (0.05-500 mg/L). In conclusion, BPA could have immunotoxicity to Carassius auratus and functional changes of lymphocyte and macrophage in Carassius auratus may be different between low and high dosages.

  8. JPRS Report: Proliferation Issues

    Science.gov (United States)

    2016-03-24

    Industry (MITI) plans to hold a seminar on arms export control as early as this fall in an Asian country. The countries include Indonesia, Malaysia ...NPT BK1703072393 Kuala Lumpur BERNAMA in English 0604 GMT 17 Mar 93 [Text] Kuala Lumpur, March 17 (OANA/ BERNAMA)— Malaysia Wednesday, expressed ...JPRS-TND-93-009 29 March 1993 !■■■■! FOREIGN BROADCAST INFORMATION SERVICE JPRS Report— Proliferation Issues Sapsevsd tea ßubSa t©l©ɛ

  9. NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

    Science.gov (United States)

    Teixeira, Leonardo K; Carrossini, Nina; Sécca, Cristiane; Kroll, José E; DaCunha, Déborah C; Faget, Douglas V; Carvalho, Lilian D S; de Souza, Sandro J; Viola, João P B

    2016-09-01

    The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

  10. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

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

    2006-09-01

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

  11. Chronic lymphocytic leukemia: present status.

    Science.gov (United States)

    Montserrat, E; Rozman, C

    1995-03-01

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

  12. Lymphocyte subsets in pediatric migraine.

    Science.gov (United States)

    Cseh, Aron; Farkas, Kristof Mark; Derzbach, Laszlo; Muller, Katalin; Vasarhelyi, Barna; Szalay, Balazs; Treszl, Andras; Farkas, Viktor

    2013-07-01

    Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

  13. Obinutuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

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

  14. 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.

  15. Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

    Science.gov (United States)

    Benitez-Trinidad, A B; Herrera-Moreno, J F; Vázquez-Estrada, G; Verdín-Betancourt, F A; Sordo, M; Ostrosky-Wegman, P; Bernal-Hernández, Y Y; Medina-Díaz, I M; Barrón-Vivanco, B S; Robledo-Marenco, M L; Salazar, A M; Rojas-García, A E

    2015-06-01

    Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 μM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect.

  16. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG; Yong; LI; Ming-chun; FU; Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation. Methods Animals were divided into three groups (n = 10), they were animals exposed to radiation (Rad), normal control animals (Ctr), and irradiated animals treated with LTN (Rad + LTN). Animal model of chronic radiation stress injury was induced by irradiating mice with 60 Co γ-ray for 6 weeks from Monday to Friday consecutively. Before radiation, the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL), whereas mice in other groups were injected with 0.9% physiological saline. The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen. The cell numbers and viability of T lymphocytes, which were isolated from the spleen, were determined by Trypan blue staining. Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured. Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes, associated with reduced T lymphocytes viability and functions, and elevated NO production. Treatment with LTN significantly normalized the elevated NO production, and attenuated the negative outcomes resulting from radiation mentioned above. Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  17. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; LI Ming-chun; FU Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation.Methods Animals were divided into three groups (n =10),they were animals exposed to radiation (Rad),normal control animals (Ctr),and irradiated animals treated with LTN (Rad + LTN).Animal model of chronic radiation stress injury was induced by irradiating mice with 60Co γ-ray for 6 weeks from Monday to Friday consecutively.Before radiation,the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL),whereas mice in other groups were injected with 0.9% physiological saline.The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen.The cell numbers and viability of T lymphocytes,which were isolated from the spleen,were determined by Trypan blue staining.Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured.Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes,associated with reduced T lymphocytes viability and functions,and elevated NO production.Treatment with LTN significantly normalized the elevated NO production,and attenuated the negative outcomes resulting from radiation mentioned above.Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  18. Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Monobe, Manami [Chiba Univ. (Japan). Graduate School of Science and Technology; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-09-01

    We here investigated and reported the effects of beer drinking on radiation-induced chromosome aberrations in blood lymphocytes. Human blood that was collected either before or after drinking a 700 ml beer was in vitro irradiated with 200 kVp X rays or 50 keV/{mu}m carbon ions. The relation between the radiation dose and the aberration frequencies (fragments and dicentrics) was significantly (P<0.05) lower for lymphocytes collected 3 h after beer drinking than those before drinking. Fitting the dose response to a linear quadratic model showed that the alpha term of carbon ions was significantly (P<0.05) decreased by beer drinking. A decrease of dicentric formation was detected as early as 0.5 h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of lymphocytes was higher after beer drinking than before, indicating that a division delay would not be responsible for the low aberrations induced by beer drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which corresponded to a concentration of 6-times higher than the maximum ethanol concentration in the blood after beer drinking, reduced the dicentric formation caused by X-ray irradiation, but not by carbon-ion irradiation. The beer-induced reduction of dicentric formation was not affected by serum. It is concluded that beer could contain non-ethanol elements that reduce the chromosome damage of lymphocytes induced by high-LET radiation. (author)

  19. Bilateral dacryoadenitis complicated by lymphocytic hypophysitis.

    Science.gov (United States)

    Baoke, Hou; Shihui, Wei; Maonian, Zhang; Zhaohui, Li; Zhitong, Zou; Zhigang, Song; Yan, Hei

    2009-09-01

    Three patients developed dacryoadenitis (DA) or lymphocytic pneumonitis before the diagnosis of lymphocytic hypophysitis (LyH). There were two previous reports of concurrence of DA and LyH. Our patients add support to the idea that DA and LyH are manifestations of a systemic autoimmune disease. We suggest that the discovery of DA should prompt imaging and endocrine investigation of LyH.

  20. Expression of tenascin in lymphocytic autoimmune thyroiditis.

    OpenAIRE

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

    1997-01-01

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

  1. Role of extracellular signal-regulated kinase in regulating expression of interleukin 13 in lymphocytes from an asthmatic rat model

    Institute of Scientific and Technical Information of China (English)

    LI Yuan-yuan; LIU Xian-sheng; LIU Chang; XU Yong-jian; XIONG Wei-xing

    2010-01-01

    Background The extracellular signal-regulated kinase (ERK) is widely expressed in mammal cells and involved in airway proliferation and remodeling in asthma. In this study, we intend to explore the role of ERK in the expression of the Th2 cytokine, interleukin 13 (IL-13) in lymphocytes in asthma.Methods Forty Sprague-Dawley rats were randomly divided into two groups: normal control and asthmatic groups. Peripheral blood lymphocytes were isolated and purified from the blood of each rat and divided into five groups: control, asthmatic lymphocytes, asthmatic cells stimulated with ERK activator epidermal growth factor (EGF), or with ERK inhibitor PD98059, or with EGF and PD98059 together. The expression of phosphorylated-ERK (p-ERK) was observed by immunocvtochemical staining, the expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein in supernatants was measured by ELISA.Results (1) The ERK mRNA level and the percentage of cells with p-ERK in lymphocytes from asthmatic rats were significantly higher than those in normal controls, and were significantly increased by EGF administration. This effect of EGF was significantly inhibited by PD98059 pretreatment. (2) IL-13 protein in supematants of asthmatic lymphocytes was higher than that produced by normal control lymphocytes, and was significantly increased by EGF treatment. This EGF effect was partly blocked by PD98059 pretreatment. (3) There was a significant positive correlation between the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13 protein in supematants of lymphocytes from asthmatic rats.Conclusions In asthma the ERK expression and activation levels were increased, as was the protein level of IL-13. The ERK signaling pathway may be involved in the increased expression of the Th2 cytokine IL-13 in asthma.

  2. Initiatives for proliferation prevention

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy`s (DOE`s) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway.

  3. Lymphocyte migration into syngeneic implanted lymph nodes

    Energy Technology Data Exchange (ETDEWEB)

    Gordeeva, M.S.

    1986-03-01

    To judge the functional activity of lymphocytes of an implanted lymph node (LN), the proliferative response of lymphocytes of the implanted organ in the blast-transformation reaction in vitro and their ability to induce a local graft versus host reaction (GVHR) were determined. The lymphocyte suspension for labeling with /sup 51/Cr was obtained from peripheral LN in different situations from syngeneic mice. The resulting lymphocyte suspension was labeled with a solution of sodium chromate-/sup 51/Cr in a concentration of 20-40 microCi/100.10/sup 6/ cells in 1 ml for 40 min at 37/sup 0/C. The proliferative activity of a suspension of lymphocytes was estimated as incorporation of /sup 3/H-thymidine into DNA during incubation of the cell suspension for 3 days. Data on migration of /sup 51/Cr-labeled cells and the results of the morphological observations revealed marked ability of lymphocytes of the peripheral pool to colonize the regenerating stroma.

  4. Prenatal ontogeny of lymphocyte subpopulations in pigs.

    Science.gov (United States)

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

    1998-12-01

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

  5. 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.

  6. Anergy in self-directed B lymphocytes from a statistical mechanics perspective

    CERN Document Server

    Agliari, Elena; Del Ferraro, Gino; Guerra, Francesco; Tantari, Daniele

    2012-01-01

    The ability of the adaptive immune system to discriminate between self and non-self mainly stems from the ontogenic clonal-deletion of lymphocytes expressing strong binding affinity with self-peptides. However, some self-directed lymphocytes may evade selection and still be harmless due to a mechanism called clonal anergy. As for B lymphocytes, two major explanations for anergy developed over three decades: according to "Varela theory", it stems from a proper orchestration of the whole B-repertoire, in such a way that self-reactive clones, due to intensive interactions and feed-back from other clones, display more inertia to mount a response. On the other hand, according to the `two-signal model", which has prevailed nowadays, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. The first result we present, achieved through disordered statistical mechanics, shows that helper cells do not prompt the activation and proliferation of a certain sub-group of ...

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

    Directory of Open Access Journals (Sweden)

    Li-Xin Sun

    2014-01-01

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

  8. Construction of HA-1-DC Nucleic-acid Vaccine and Induction of Specific Cytotoxic T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    WANG Yaya; ZHANG Donghua; HU Jinmei; LIU Wenli; ZHOU hongsheng; ZHANG Lu; LIU Dan; HUANG Zhenqian; TAN Huo

    2007-01-01

    An HA-1-DC nucleic-acid vaccine was constructed to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). DCs were generated from HSCT donors in vitro, and its immunologic activity was assayed by using flow cytometry and mixed lymphocytes reaction.HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic-acid vaccine. After transfection for 48 h, the expression of HA-1 protein could be detected by using Western blot. The DCs were cultured with syngenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs).The cytoxicity of the CTLs was detected by LDH assay. The results showed that The DCs derived from peripheral blood monocytes (PBMCs) expressed the phenotype of DCs, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48-h, HA-1 protein was detected by using Western blot. The cytotoxity of inducing CTLs was higher than the control group. It was suggested that minor histocompatibility antigen HA-1 could be considered as a target of immunotherapy against leukemia after HSCT.

  9. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

    Science.gov (United States)

    Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos

    2014-06-01

    Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.

  10. Cytotoxic T lymphocyte antigen-4 (CTLA-4 A49G polymorphism and autoimmune blood diseases

    Directory of Open Access Journals (Sweden)

    Faruk Aktürk

    2010-06-01

    Full Text Available Objective: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4 is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. Material and Methods: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA, 62 patients with immune thrombocytopenic purpura (ITP, and 150 healthy individuals. Results: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL patients with AIHA (n=4, all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG. There was no significant statistical association between G allele and systemic lupus erythematosus (SLE or AIHA.Conclusion: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

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

    Science.gov (United States)

    2017-07-24

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

  12. The anticancer homeopathic composite "Canova Method" is not genotoxic for human lymphocytes in vitro.

    Science.gov (United States)

    Seligmann, Igor C; Lima, Patrícia D L; Cardoso, Plínio C S; Khayat, André S; Bahia, Marcelo O; Buchi, Dorli de Freitas; Cabral, Isabel R; Burbano, Rommel R

    2003-06-30

    The Canova Method (CM) is a homeopathic medicine indicated for the treatment of patients with cancer and for pathologies that involve a depressed immune system, such as AIDS. This product is composed of homeopathic dilutions of Aconitum napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom and Thuya occidentalis. It stimulates the immune system by activating macrophages. Activated macrophages stimulate the lymphocytes so that they increase their cytotoxic action in response to tumoral growth or infection. Given that the CM stimulates and accelerates the activity of macrophages and lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated with this homeopathic medication in vitro. Structural and numerical chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index was considered as a monitor for induced cellular toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following final concentrations of the medicinal composite CM: 4, 8 and 12%. Treatments with the CM did not affect mitotic indexes, nor did they provoke chromosomal aberrations, when compared with untreated controls. There was no cytotoxicity or genotoxicity at the chromosomal level.

  13. Chromosomal aberrations in ovine lymphocytes exposed in vitro to tolylfluanid.

    Science.gov (United States)

    Sutiaková, Irena; Kovalkovičová, Natália; Sutiak, Václav

    2012-01-01

    Chromosomal aberrations have been used as important cytogenetic biomarkers to study the mutagenic effects of different chemicals in vivo and in vitro. Chromosomal aberrations were evaluated in cultures of sheep lymphocytes in vitro exposed to the fungicide tolylfluanid. Lymphocyte cultures from three donors were exposed to four different concentrations of fungicide (1.10(-4) M(.)L; 1.10(-5) M(.)L; 1.10(-6) M(.)L; 1 × 10(-7) M(.)L). Chromosomal analysis showed a significant (P = 0.018 and 0.038 respectively, Anova test, P Tukey test) increase in the frequency of aberrant cells (ABC) in cultures treated with the highest negative experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L) compared to control. Significantly increased numbers of chromatid breaks (7.67 ± 0.58% against 1.67 ± 2.08%, P = 0.009, Anova test, P Tukey test) and chromatid gaps (7.67 ± 1.15% against 2.67 ± 0.58%, P = 0.003, Anova test, P Tukey test) were observed in ovine cultures treated with the highest experimental concentration of tolylfluanid (1.10(-4) M(.)L). Tolylfluanid induced also chromosomal exchanges (P = 0.038, and 0.016 respectively, Anova test, P Tukey test) in ovine cultures treated with the highest experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L). The mitotic index has not shown any statistical differences between the various treatments and control groups. Our results suggest a significant genotoxic effect of tolylfluanid only at the highest concentration in sheep peripheral lymphocytes in vitro.

  14. Uncertainties in Nuclear Proliferation Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chul Min; Yim, Man-Sung; Park, Hyeon Seok [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2015-05-15

    There have been various efforts in the research community to understand the determinants of nuclear proliferation and develop quantitative tools to predict nuclear proliferation events. Such systematic approaches have shown the possibility to provide warning for the international community to prevent nuclear proliferation activities. However, there are still large debates for the robustness of the actual effect of determinants and projection results. Some studies have shown that several factors can cause uncertainties in previous quantitative nuclear proliferation modeling works. This paper analyzes the uncertainties in the past approaches and suggests future works in the view of proliferation history, analysis methods, and variable selection. The research community still lacks the knowledge for the source of uncertainty in current models. Fundamental problems in modeling will remain even other advanced modeling method is developed. Before starting to develop fancy model based on the time dependent proliferation determinants' hypothesis, using graph theory, etc., it is important to analyze the uncertainty of current model to solve the fundamental problems of nuclear proliferation modeling. The uncertainty from different proliferation history coding is small. Serious problems are from limited analysis methods and correlation among the variables. Problems in regression analysis and survival analysis cause huge uncertainties when using the same dataset, which decreases the robustness of the result. Inaccurate variables for nuclear proliferation also increase the uncertainty. To overcome these problems, further quantitative research should focus on analyzing the knowledge suggested on the qualitative nuclear proliferation studies.

  15. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  16. INTENSITY OF APOPTOTIC AND PROLIFERATIVE EVENTS IN LYMPHOCYTES UNDER DYSLIPIDEMIC CONDITIONS AT EARLY STAGES OF CHRONIC BRAIN ISCHEMIA

    Directory of Open Access Journals (Sweden)

    A. V. Zurochka

    2014-01-01

    Full Text Available Incidence of different types of dislipoproteinemias (DLPs and a balance between apoptosis andproliferation of lymphocytes were studied in males exhibiting initial manifestations of cerebral blood flowinsufficiency (ICBI. In general, high intensity of lymphocyte activation was revealed in patients with ICBI,with amplified proliferative potential demonstrable in this group. We have also shown a trend to increasednumbers of T and B lymphocytes expressing antiapoptogenic bcl-2 protein. The changes in apoptosis and cellproliferation intensity were more pronounced in IIA and IIB types of DLP. In these groups, unidirectionalchanges of FasR expression were observed. However, the parameters reflecting readiness to apoptosis werechanged multidirectionally. Cholesterol and oxysterols transported to the cells under excessive dyslipidemiamay influence activities of transcription factor genes (bcl-2, Fas-regulatory gene (TDAG51, thus, probably,causing an imbalance between cellular proliferation and apoptosis.

  17. Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin

    Directory of Open Access Journals (Sweden)

    Hansen Peter J

    2008-01-01

    Full Text Available Abstract Background Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS, inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3 cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL-8 by PC-3 cells was also determined. Finally, it was tested whether OvUS blocks specific steps in the cell cycle using both PC-3 cells and lymphocytes. Results Recombinant OvUS blocked proliferation of PC-3 cells at concentrations as low as 8 μg/ml as determined by measurements of [3H]thymidine incorporation or ATP content per well. Treatment of PC-3 cells with OvUS did not cause cytotoxicity or apoptosis or alter interleukin-8 secretion into medium. Results from flow cytometry experiments showed that OvUS blocked the entry of PC-3 cells into S phase and the exit from G2/M phase. In addition, OvUS blocked entry of lymphocytes into S phase following activation of proliferation with phytohemagglutinin. Conclusion Results indicate that OvUS acts to block cell proliferation through disruption of the cell cycle dynamics rather than induction of cytotoxicity or apoptosis. The finding that OvUS can regulate cell proliferation makes this one of only a few serpins that function to inhibit cell growth.

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

    Science.gov (United States)

    2013-06-03

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

  19. DNA strand breaks (comet assay) in blood lymphocytes from wild bottlenose dolphins.

    Science.gov (United States)

    Lee, Richard F; Bulski, Karrie; Adams, Jeffrey D; Peden-Adams, Margie; Bossart, Gregory D; King, Lydia; Fair, Patricia A

    2013-12-15

    The comet assay was carried out on blood lymphocytes from a large number of wild dolphins (71 from Indian River Lagoon, FL, USA; 51 from Charleston Harbor, SC, USA) and provides a baseline study of DNA strand breaks in wild dolphin populations. There were no significant differences in the comet assay (% DNA in tail) results between the different age and sex categories. Significant difference in DNA strand breaks were found between Charleston Harbor dolphins (median--17.4% DNA in tail) and Indian River Lagoon dolphins (median--14.0% DNA in tail). A strong correlation found between T-cell proliferation and DNA strand breaks in dolphin lymphocytes suggests that dolphins with a high numbers of DNA strand breaks have a decreased ability to respond to infection. Higher concentrations of genotoxic agents in Charleston Harbor compared with Indian River lagoon may have been one of the causes of higher DNA strand breaks in these dolphins.

  20. Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.

    Science.gov (United States)

    Grzegorzewska, Alicja E; Leander, Magdalena

    2005-01-01

    Dietary deficiency causes abnormalities in circulating lymphocyte counts. For the present paper, we evaluated correlations between total and subpopulation lymphocyte counts (TLC, SLCs) and parameters of nutrition in peritoneal dialysis (PD) patients. Studies were carried out in 55 patients treated with PD for 22.2 +/- 11.4 months. Parameters of nutritional status included total body mass, lean body mass (LBM), body mass index (BMI), and laboratory indices [total protein, albumin, iron, ferritin, and total iron binding capacity (TIBC)]. The SLCs were evaluated using flow cytometry. Positive correlations were seen between TLC and dietary intake of niacin; TLC and CD8 and CD16+56 counts and energy delivered from protein; CD4 count and beta-carotene and monounsaturated fatty acids 17:1 intake; and CD19 count and potassium, copper, vitamin A, and beta-carotene intake. Anorexia negatively influenced CD19 count. Serum albumin showed correlations with CD4 and CD19 counts, and LBM with CD19 count. A higher CD19 count was connected with a higher red blood cell count, hemoglobin, and hematocrit. Correlations were observed between TIBC and TLC and CD3 and CD8 counts, and between serum Fe and TLC and CD3 and CD4 counts. Patients with a higher CD19 count showed a better clinical-laboratory score, especially less weakness. Patients with a higher CD4 count had less expressed insomnia. Quantities of ingested vitamins and minerals influence lymphocyte counts in the peripheral blood of PD patients. Evaluation of TLC and SLCs is helpful in monitoring the effectiveness of nutrition in these patients.

  1. Small B cell lymphocytic lymphoma presenting as obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Chang Weng-Cheng

    2004-07-01

    Full Text Available Abstract Background Most lymphomas that involve the tonsil are large B cell lymphomas. Large B-cell lymphoma is a high grade malignancy which progresses rapidly. Tonsillar lymphoma usually presents as either a unilaterally enlarged palatine tonsil or as an ulcerative and fungating lesion over the tonsillar area. Small lymphocytic lymphomas (SLL of the Waldeyer's ring are uncommon. Case presentation We report a 41-year-old male who presented with a ten-year history of snoring. Physical examination revealed smooth bilateral symmetrically enlarged tonsils without abnormal surface change or cervical lymphadenopathy. Palatal redundancy and a narrowed oropharyngeal airway were also noted. The respiratory disturbance index (RDI was 66 per hour, and severe obstruction sleep apnea (OSA was suspected. No B symptoms, sore throat, odynophagia or dysphagia was found. We performed uvulopalatopharyngoplasty (UPPP and pathological examination revealed incidental small B-cell lymphocytic lymphoma (SLL. Conclusion It is uncommon for lymphoma to initially present as OSA. SLL is an indolent malignancy and is not easy to detect in the early stage. We conclude that SLL may be a contributing factor of OSA in the present case.

  2. Cyclosporin A Inhibits Smooth Muscle Proliferation in the Vascular Response to Injury

    Science.gov (United States)

    Jonasson, Lena; Holm, Jan; Hansson, Goran K.

    1988-04-01

    The arterial response to injury is dominated by proliferation of smooth muscle cells and infiltration of blood-borne cells in the vascular intima. Arterial smooth muscle cell proliferation is under growth factor control, but how this regulation operates in vivo is unclear. We studied the effect on arterial response to mechanical injury of cyclosporin A, a drug that inhibits T-lymphocyte activation. Cyclosporin A treatment at surgery caused a persistent inhibition of the intimal proliferative lesion. Cyclosporin A also inhibited expression of Ia antigens on smooth muscle cells in situ but had no direct effects on smooth muscle cell proliferation in culture. Therefore, the inhibition of intimal cell proliferation appears to be mediated via the immune system.

  3. Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry

    Science.gov (United States)

    Orr, Stephen J; Boutz, Daniel R; Wang, Rong; Chronis, Constantinos; Lea, Nicholas C; Thayaparan, Thivyan; Hamilton, Emma; Milewicz, Hanna; Blanc, Eric; Mufti, Ghulam J; Marcotte, Edward M; Thomas, N Shaun B

    2012-01-01

    Regulating the transition of cells such as T lymphocytes from quiescence (G0) into an activated, proliferating state involves initiation of cellular programs resulting in entry into the cell cycle (proliferation), the growth cycle (blastogenesis, cell size) and effector (functional) activation. We show the first proteomic analysis of protein interaction networks activated during entry into the first cell cycle from G0. We also provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells. We employed a proteomic profiling method to identify large-scale changes in chromatin/nuclear matrix-bound and unbound proteins in human T lymphocytes during the transition from G0 into the first cell cycle and mapped them to form functionally annotated, dynamic protein interaction networks. Inhibiting the induction of two proteins involved in two of the most significantly upregulated cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4), showed, respectively, that human T cells can enter the cell cycle without growing in size, or increase in size without entering the cell cycle. PMID:22415777

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

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

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

  5. The cytogenetic effects of black tea and green tea on cultured human lymphocytes

    Directory of Open Access Journals (Sweden)

    Halil Erhan Eroğlu

    2011-12-01

    Full Text Available In this study, the cytogenetic effects of black tea and green tea were determined in cultured peripheral blood lymphocytes. Results showed that black tea and green tea induced the mitotic and replication indexes and decreased micronuclei. But these data were not statistically significant for green tea. The effects of black tea on the micronucleus formation and mitotic index were statistically significant. The decrease in micronucleus counts indicated that black tea and green tea had considerable anticlastogenic and antigenotoxic effects as observed in vitro in human lymphocytes. Thus, it could be concluded that tea polyphenols protected the normal cells from genotoxic or carcinogenic agents, which indicated the therapeutic and antioxidative role of catechins, flavonoids or other tea compounds.

  6. Lymphopenia-induced proliferation in the absence of functional Autoimmune regulator (Aire) induces colitis in mice.

    Science.gov (United States)

    Kekäläinen, Eliisa; Lehto, Maija-Katri; Smeds, Eero; Pöntynen, Nora; Pekkarinen, Pirkka T; Ulmanen, Ismo; Miettinen, Aaro; Arstila, T Petteri

    2015-09-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in Autoimmune regulator (Aire), a transcriptional regulator of negative selection in thymus. However, Aire is also expressed in periphery, but the full range of Aire's peripheral function is unknown. Here, we transferred lymphocytes from wildtype donors into lymphopenic recipients with or without functional Aire. Following cell proliferation thus took place in Aire-sufficient or deficient environment. The wildtype lymphocytes hyperproliferated and induced disease in lymphopenic Aire(-/-) but not in Aire(+/+) recipients. The disease was characterized by diarrhea, inflammation, and colitis, and in some recipients pancreatitis, gastritis, and hepatitis was also found. Our results identify Aire as an important regulator of peripheral T cell homeostasis in gastrointestinal tissues. Given a suitable trigger the absence of peripheral Aire leads to dysregulated T cell proliferation and disease. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  7. Carbon nanotube-mediated delivery of nucleic acids does not result in non-specific activation of B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Cai Dong [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Doughty, Cheryl A [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Potocky, Terra B [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Dufort, Fay J [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Huang Zhongping [NanoLab, Incorporated, Newton, MA 02458 (United States); Blair, Derek [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Kempa, Krzysztof [Department of Physics, Boston College, Chestnut Hill, MA 02467 (United States); Ren, Z F [Department of Physics, Boston College, Chestnut Hill, MA 02467 (United States); Chiles, Thomas C [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States)

    2007-09-12

    The efficient delivery of genes and proteins into primary mammalian cells and tissues has represented a formidable challenge. Recent advances in the research of carbon nanotubes (CNTs) offer much promise for their use as delivery platforms into mammalian cells. Ideally, CNT-mediated applications should not result in cellular toxicity nor perturb cellular homeostasis (e.g., result in non-specific activation of primary cells). It is therefore critical to evaluate the impact of CNT exposure on the cellular metabolism, proliferation and survival of primary mammalian cells. We investigated the compatibility of a recently developed CNT-mediated delivery method, termed nanospearing, with primary ex vivo cultures of B lymphocytes. Several parameters were evaluated to assess the impact of CNTs on naive B lymphocytes, including cell survival, activation, proliferation and intracellular signal transduction. Our results indicate that nanospearing does not result in the activation of naive primary B lymphocytes nor alter survival in ex vivo cultures. Herein, B cells exposed to CNTs were capable of responding to extrinsic pro-survival signals such as interleukin-4 and signaling by the B-cell antigen receptor in a manner similar to that of B cells cultured in the absence of CNTs. Our study demonstrates the biocompatibility of the CNT-mediated nanospearing procedure with respect to primary B lymphocytes.

  8. Anti-inflammatory effects of novel barbituric acid derivatives in T lymphocytes.

    Science.gov (United States)

    Xu, Chenjia; Wyman, Arlene R; Alaamery, Manal A; Argueta, Shannon A; Ivey, F Douglas; Meyers, John A; Lerner, Adam; Burdo, Tricia H; Connolly, Timothy; Hoffman, Charles S; Chiles, Thomas C

    2016-09-01

    We have used a high throughput small molecule screen, using a fission yeast-based assay, to identify novel phosphodiesterase 7 (PDE7) inhibitors. One of the most effective hit compounds was BC12, a barbituric acid-based molecule that exhibits unusually potent immunosuppressive and immunomodulatory actions on T lymphocyte function, including inhibition of T cell proliferation and IL-2 cytokine production. BC12 treatment confers a >95% inhibition of IL-2 secretion in phytohaemagglutinin (PHA) plus phorbol-12-myristate-13-acetate (PMA) stimulated Jurkat T cells. The effect of BC12 on IL-2 secretion is not due to decreased cell viability; rather, BC12 blocks up-regulation of IL-2 transcription in activated T cells. BC12 also inhibits IL-2 secretion in human peripheral T lymphocytes stimulated in response to CD3/CD28 co-ligation or the combination of PMA and ionomycin, as well as the proliferation of primary murine T cells stimulated with PMA and ionomycin. A BC12 analog that lacks PDE7 inhibitory activity (BC12-4) displays similar biological activity, suggesting that BC12 does not act via PDE7 inhibition. To investigate the mechanism of inhibition of IL-2 production by BC12, we performed microarray analyses using unstimulated and stimulated Jurkat T cells in the presence or absence of BC12 or BC12-4. Our studies show these compounds affect the transcriptional response to stimulation and act via one or more shared targets to produce both anti-inflammatory and pro-stress effects. These results demonstrate potent immunomodulatory activity for BC12 and BC12-4 in T lymphocytes and suggest a potential clinical use as an immunotherapeutic to treat T lymphocyte-mediated diseases.

  9. Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

    OpenAIRE

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Despite significant advances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cel...

  10. Trajectory Indexing Using Movement Constraints

    DEFF Research Database (Denmark)

    Pfoser, D.; Jensen, Christian Søndergaard

    2005-01-01

    With the proliferation of mobile computing, the ability to index efficiently the movements of mobile objects becomes important. Objects are typically seen as moving in two-dimensional (x,y) space, which means that their movements across time may be embedded in the three-dimensional (x,y,t) space....... Further, the movements are typically represented as trajectories, sequences of connected line segments. In certain cases, movement is restricted; specifically, in this paper, we aim at exploiting that movements occur in transportation networks to reduce the dimensionality of the data. Briefly, the idea...... is to reduce movements to occur in one spatial dimension. As a consequence, the movement occurs in two-dimensional (x,t) space. The advantages of considering such lower-dimensional trajectories are that the overall size of the data is reduced and that lower-dimensional data is to be indexed. Since off...

  11. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

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

  12. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

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

    2016-01-01

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

  13. 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......+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months...... to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p Breastfeeding might have both a current and long...

  14. 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.

  15. Induction of chromosomal aberrations in human lymphocytes by fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da; Coelho, Paulo Rogerio Pinto; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br

    2009-07-01

    Chromosome aberrations induced by sparsely ionizing radiation (low-LET) are well known and cytogenetic analyses of irradiated human lymphocytes have been widely applied to biological dosimetry. However, much less is known about chromosome aberrations induced by densely ionizing radiation (high LET), such as that of alpha particles or neutrons. Such particles induce DNA strand breaks, as well as chromosome breakage and rearrangements of high complexity. This damage is more localized and less efficiently repaired than after X- or {gamma}-ray irradiation. This preferential production of complex aberrations by densely ionizing radiation is related to the unique energy deposition patterns, which produces highly localized multiple DNA damage at the chromosomal level. A better knowledge of the interactions between different types of radiation and cellular DNA is of importance, not only from the radiobiological viewpoint but also for dosimetric and therapeutic purposes. The objective of the present study was to analyse the cytogenetic effects of fission neutrons on peripheral blood lymphocytes in order to evaluate structural and numerical aberrations and number of cells in the different mitotic cycles. So, blood samples from five healthy donors, 22-25 years old, of both sexes, were irradiated in the Research Reactor IEA-R1 of our Institute (IPEN/CNEN-SP) with thermal and fast neutrons at doses of 0.2; 0.3; 0.5 and 1.0 Gy. The {gamma} contribution to the total absorbed dose was about 30%. These doses were monitored by thermoluminescent dosemeters: LiF-600 (for neutrons) and LiF-700 (for {gamma}-rays). The data concerning structural aberrations were evaluated with regard to three parameters: percentage of cells with aberrations, number of aberrations/cell and number of dicentric/cell. The cytogenetic results showed an increase in the three parameters after irradiation with neutrons, as a function of radiation dose. Apparently, there was no influence of neutrons on the

  16. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    OpenAIRE

    2011-01-01

    INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulate...

  17. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon mi...

  18. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon...

  19. Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine

    Directory of Open Access Journals (Sweden)

    Li B

    2016-11-01

    Full Text Available Bo Li,1,2 Michael Siuta,1 Vanessa Bright,1,2 Dmitry Koktysh,3,4 Brittany K Matlock,5 Megan E Dumas,1 Meiying Zhu,1 Alex Holt,1 Donald Stec,3,6 Shenglou Deng,7 Paul B Savage,7 Sebastian Joyce,8,9 Wellington Pham1,2,6,10–12 1Institute of Imaging Science, Vanderbilt University School of Medicine, 2Department of Radiology and Radiological Sciences, 3Department of Chemistry, Vanderbilt University, 4Vanderbilt Institute of Nanoscale Science and Engineering, 5Vanderbilt Flow Cytometry Shared Resource, Vanderbilt University, 6Vanderbilt Institute of Chemical Biology, 7Department of Chemistry and Biochemistry, Brigham Young University, 8Department of Pathology, Microbiology and Immunology, Vanderbilt University, 9Veterans Administration Tennessee Valley Healthcare System, 10Department of Biomedical Engineering, 11Vanderbilt Ingram Cancer Center, 12Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA Abstract: The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova and an adjuvant within the poly(lactic-co-glycolic acid nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days. The in vivo immunization studies exhibited that the nanovaccine induced stronger and longer immune responses compared to its soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced more robust antigen-specific CD8+ T cell response than intraperitoneal injection of nanovaccine. Keywords: nanovaccine, dendritic cells, GalCer, inhalable vaccine

  20. Consequences of TCDD treatment on intra-hepatic lymphocytes during liver regeneration.

    Science.gov (United States)

    Horras, Christopher J; Lamb, Cheri L; King, Allie L; Hanley, Jason R; Mitchell, Kristen A

    2012-01-01

    Increasing evidence demonstrates a physiological role for the aryl hydrocarbon receptor (AhR) in regulating hepatocyte cell cycle progression. Previous studies have used a murine model of liver regeneration to show that exposure to the potent exogenous AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), suppresses hepatocyte proliferation in vivo. Based on recent reports that natural killer (NK) cells negatively regulate liver regeneration, coupled with the well-established immunomodulatory effects of TCDD, it was hypothesized that alterations in lymphocyte activation contribute to the suppression of liver regeneration in TCDD-treated mice. To test this, mice were treated with TCDD (20 μg/kg) 1 day prior to 70% partial hepatectomy (PH), in which two-thirds of the liver was surgically resected. Lymphocytes were collected from the remnant liver and analyzed by flow cytometry. Whereas exposure to TCDD did not alter the number of NK cells or CD3(+) T-cells recovered from the regenerating liver, it reduced the percentage and number of intra-hepatic NKT cells 42 h after PH. With regard to lymphocyte activation, TCDD treatment transiently increased CD69 expression on NK and NKT cells 12 h after PH, but had no effect on intracellular levels of IFNγ in NK, NKT, or CD3(+) T-cells. To determine the relevance of NK cells to the suppression of liver regeneration by TCDD, mice were treated with anti-Asialo GM-1 (ASGM-1) antibody to deplete NK cells prior to TCDD treatment and PH, and hepatocyte proliferation was measured using bromodeoxyuridine incorporation. Exposure to TCDD was found to inhibit hepatocyte proliferation in the regenerating liver of NK cell-depleted mice and control mice to the same extent. Hence, it is unlikely that enhanced numbers or increased activation of NK cells contribute to the suppression of liver regeneration in TCDD-treated mice.

  1. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Klein, George, E-mail: Georg.Klein@ki.se [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden); Klein, Eva; Kashuba, Elena [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden)

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  2. Hepatic granulomas induced by Schistosoma mansoni in mice deficient for connexin 43 present lower cell proliferation and higher collagen content.

    Science.gov (United States)

    Oloris, Silvia Catarina Salgado; Mesnil, Marc; Reis, Viviane Neri de Souza; Sakai, Mônica; Matsuzaki, Patrícia; Fonseca, Evelise de Souza Monteiro; da Silva, Tereza Cristina; Avanzo, José Luís; Sinhorini, Idércio Luiz; Guerra, José Luiz; Costa-Pinto, Frederico Azevedo; Maiorka, Paulo Cesar; Dagli, Maria Lúcia Zaidan