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

NARCIS (Netherlands)

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

2001-01-01

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

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

Science.gov (United States)

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

2010-02-01

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

Organ distribution of 111In-oxine labeled lymphocytes in normal subjects and in patients with chronic lymphocytic leukemia and malignant lymphoma

International Nuclear Information System (INIS)

Matsuda, Shin; Uchida, Tatsumi; Yui, Tokuo; Kariyone, Shigeo

1982-01-01

T and B lymphocyte survival and organ distribution were studied by using 111 In-oxine labeled autologous lymphocytes in 3 normal subjects, 3 patients with chronic lymphocytic leukemia (CLL) and 9 with malignant lymphoma (ML).FDisappearance curves of the labeled lymphocytes showed two exponential components in all cases. The half time of the first component was within 1 hour in all cases. That of the second one was 50.7 +- 6.4 hours for all lymphocytes, 52.0 +- 5.5 hours for T lymphocytes and 31.6 +- 4.9 hours for B lymphocytes in normal subjects, 192.6 hours for T-CLL and 57.7 +- 46.9 hours for B-CLL, and 60.2 +- 30.7 hours for T cell type of malignant lymphoma (T-ML) and 63.7 +- 24.5 hours for B cell type of malignant lymphoma (B-ML). These data might suggest that all lymphocyte disappearance curve reflected T lymphocyte disappearance curve chiefly, and the half time of B lymphocytes was shorter than that of T lymphocytes. In the T-CLL, the half time of the second component prolonged extremely in comparison with that of normal T lymphocytes. The labeled cells were accumulated in the lungs, spleen and liver immediately after the infusion, then in the spleen most remarkably 1 hour after the infusion in all cases. The radioactivity over the bone marrow was observed from 1 hour in all cases and that of lymph nodes were first noticed 18 hours after the infusion in T-CLL and T-ML, 68 hours in B-CLL but were not noticed in normal subjects and B-ML. The recovery of labeled cells in the blood was 28.5 +- 7.9% for all lymphocytes, 19.7 +- 1.9% for T lymphocytes and 11.0 +- 5.1% for B lymphocytes in normal subjects, 25.8 +- 1.6% for CLL, and 17.6 +- 11.0% for T-ML, 7.7 +- 5.2% for B-ML, respectively. (J.P.N.)

Radiosensitivity of lymphocytes in vitro

International Nuclear Information System (INIS)

Albrecht, S.

1979-01-01

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

GENERATION OF CYTOTOXIC LYMPHOCYTES IN MIXED LYMPHOCYTE REACTIONS

Science.gov (United States)

Forman, James; Möller, Göran

1973-01-01

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

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

SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

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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.

Laboratorial diagnosis of lymphocytic meningitis

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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.

Effect of radiotherapy on lymphocyte cytotoxicity in vitro

Energy Technology Data Exchange (ETDEWEB)

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

1975-11-01

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

Measurement of exercise-induced oxidative stress in lymphocytes.

Science.gov (United States)

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

2011-10-01

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

Metal ion levels and lymphocyte counts

DEFF Research Database (Denmark)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-11-15

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

A microculture technique for rat lymphocyte transformation.

Science.gov (United States)

Lindsay, V J; Allardyce, R A

1979-01-01

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

Damage of lymphocytes by ionizing irradiation

International Nuclear Information System (INIS)

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

1985-01-01

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

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.

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

NARCIS (Netherlands)

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

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

[The lymphocyte transformation test in dermatology].

Science.gov (United States)

Zinn, K; Braun-Falco, O

1976-03-01

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

Radiosensitivity of lymphocytes among Filipinos: final report

International Nuclear Information System (INIS)

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

1996-01-01

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

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

Science.gov (United States)

Häyry, P.; Defendi, V.

1970-01-01

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

Alteration of lymphocyte functions by 8-methoxypsoralen and longwave ultraviolet radiation. I. Suppressive effects of PUVA on T-lymphocyte migration in vitro

International Nuclear Information System (INIS)

Okamoto, H.; Takigawa, M.; Horio, T.

1985-01-01

We investigated the influence of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet radiation (PUVA) on lymphocyte migration in vitro. Nylon wool-purified, mouse splenic T lymphocytes showed locomotive responses to casein, normal mouse serum (NMS), and zymosan-activated mouse serum (ZAS). Migratory responses to casein and NMS, and to ZAS were remarkably suppressed in lymphocytes exposed to 0.5 J/cm2 UVA plus 0.1 micrograms/ml 8-MOP and to 0.8 J/cm2 UVA plus 8-MOP, respectively. The PUVA treatment used in the present study had no effect on random movement and lymphocyte viability. T lymphocytes cultured in the absence of mitogenic agent for 24 h demonstrated a greater increase in their migration activity than noncultured cells, while lymphocytes cultured after 1.0 J/cm2 PUVA pretreatment remained low. These findings suggest that the therapeutic effect of PUVA on inflammatory skin disorders may be due in part to the suppression of lymphocyte migration

B-lymphocytes as key players in chemical-induced asthma.

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Vanessa De Vooght

Full Text Available T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE. We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO mice or severe combined immunodeficiency (SCID mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI (20 µl/ear. On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+ were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl or vehicle (acetone/olive oil (AOO (controls. Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40 and consisted of B effector (Be2- (IL-4 and Be1-lymphocytes (IFN-γ. The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.

Effect of postirradiation anoxia on radiosensitivity of lymphocytes

International Nuclear Information System (INIS)

Schrek, R.

1976-01-01

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

The behavior of pig lymphocyte populations in vivo

International Nuclear Information System (INIS)

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

1986-01-01

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

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

NARCIS (Netherlands)

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

2017-01-01

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

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

NARCIS (Netherlands)

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

1977-01-01

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

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

OpenAIRE

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

2011-01-01

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

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

Science.gov (United States)

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

2017-04-01

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

Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection.

Science.gov (United States)

Ferraz, Marcela L; Gazzinelli, Ricardo T; Alves, Rosana O; Urbina, Julio A; Romanha, Alvaro J

2009-01-01

We investigated the influence of CD4(+) T lymphocytes, CD8(+) T lymphocytes, and B lymphocytes on the efficacy of posaconazole (POS) and the reference drug benznidazole (BZ) during treatment of acute Trypanosoma cruzi infection in a murine model. Wild-type mice infected with T. cruzi and treated with POS or BZ presented no parasitemia, 100% survival, and 86 to 89% cure rates, defined as the percentages of animals with negative hemocultures at the end of the observation period. CD4(+)-T-lymphocyte-knockout (KO) mice infected with T. cruzi and treated with BZ or POS controlled parasitemia during treatment, although circulating parasites reappeared after drug pressure cessation, leading to only a 6% survival rate and no cure. CD8(+)-T-lymphocyte-KO mice infected with T. cruzi and treated with POS or BZ had intermediate results, displaying discrete parasitemia after the treatment was ended, 81 and 86% survival, and cure rates of 31 and 66%, respectively. B-lymphocyte-KO mice infected with T. cruzi and treated with BZ relapsed with parasitemia 1 week after the end of treatment and had a 67% survival rate and only a 22% cure rate. In contrast, the activity of POS was much less affected in these animals, with permanent suppression of parasitemia, 100% survival, and a 71% cure rate. Our results demonstrate that abrogation of different lymphocytes' activities has distinct effects on the efficacy of POS and BZ in this experimental model, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune system.

Increased periodontal bone loss in temporarily B lymphocyte-deficient rats

DEFF Research Database (Denmark)

Klausen, B; Hougen, H P; Fiehn, N E

1989-01-01

In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T-lym......-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss.......In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T...... had significantly less periodontal bone support than controls. Anti-mu treated inoculated rats had significantly less periodontal bone support than nude and normal rats, whereas no difference was found between normal, nude, and thymus-grafted rats. It is concluded that permanent T...

Lymphocytic Pleural Effusion in Acute Melioidosis

Directory of Open Access Journals (Sweden)

Kuo-Mou Chung

2007-10-01

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

Role of interferon in lymphocyte recruitment into the skin

International Nuclear Information System (INIS)

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

1986-01-01

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

Lymphocyte receptors for pertussis toxin

Energy Technology Data Exchange (ETDEWEB)

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

1990-12-01

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

Mechanism of chlorphentermine-induced lymphocyte toxicity: initial investigations

International Nuclear Information System (INIS)

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

1986-01-01

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

Chronic lymphocytic leukemia: concepts and observations

Energy Technology Data Exchange (ETDEWEB)

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

1977-01-01

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

[Occurrence of associated tumours in chronic lymphocytic leukemia].

Science.gov (United States)

Szerafin, László; Jakó, János; Varju, Lóránt

2016-10-01

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

The effects of low dose radiation (LDR) on lymphocytes

International Nuclear Information System (INIS)

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

2001-01-01

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

Corrected Lymphocyte Percentages Reduce the Differences in Absolute CD4+ T Lymphocyte Counts between Dual-Platform and Single-Platform Flow Cytometric Approaches.

Science.gov (United States)

Noulsri, Egarit; Abudaya, Dinar; Lerdwana, Surada; Pattanapanyasat, Kovit

2018-03-13

To determine whether a corrected lymphocyte percentage could reduce bias in the absolute cluster of differentiation (CD)4+ T lymphocyte counts obtained via dual-platform (DP) vs standard single-platform (SP) flow cytometry. The correction factor (CF) for the lymphocyte percentages was calculated at 6 laboratories. The absolute CD4+ T lymphocyte counts in 300 blood specimens infected with human immunodeficiency virus (HIV) were determined using the DP and SP methods. Applying the CFs revealed that 4 sites showed a decrease in the mean bias of absolute CD4+ T lymphocyte counts determined via DP vs standard SP (-109 vs -84 cells/μL, -80 vs -58 cells/μL, -52 vs -45 cells/μL, and -32 vs 1 cells/μL). However, 2 participating laboratories revealed an increase in the difference of the mean bias (-42 vs -49 cells/μL and -20 vs -69 cells/μL). Use of the corrected lymphocyte percentage shows potential for decreasing the difference in CD4 counts between DP and the standard SP method.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Detection of cardiac transplant rejection with radiolabeled lymphocytes

International Nuclear Information System (INIS)

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

1982-01-01

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

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

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Jacobsen, N

1987-01-01

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

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

Science.gov (United States)

Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

2018-05-22

The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNF-α therapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNF-α therapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on

Lymphocytic gastritis--prospective study of its relationship with varioliform gastritis.

Science.gov (United States)

Haot, J; Jouret, A; Willette, M; Gossuin, A; Mainguet, P

1990-01-01

Lymphocytic gastritis is a new histopathological entity characterised by a dense lymphocytic infiltration of surface and pit gastric epithelium. Previous retrospective work has suggested that lymphocytic gastritis is related to an endoscopic form of gastropathy comprising enlarged folds, nodules and erosions, commonly denoted as varioliform gastritis. In the present prospective study, the relationship is clearly shown; nearly 82% (54/66) of the varioliform gastritis observed in four different endoscopy units correspond histologically to lymphocytic gastritis. The correlation is even better if cases showing strictly antral localisation are excluded (53/55) - that is, more than 96%. The histological concept of lymphocytic gastritis seems, however, to extend beyond varioliform gastritis as of 67 cases of lymphocytic gastritis diagnosed during the period under study, one third had no particular endoscopic expression. Images Figure 1 Figure 2 PMID:2323590

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...

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

Science.gov (United States)

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

2016-07-01

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

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

DEFF Research Database (Denmark)

Langhoff, E; Ladefoged, J; Ødum, Niels

1986-01-01

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

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

OpenAIRE

Shiratsuchi, H; Tsuyuguchi, I

1981-01-01

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

21 CFR 864.8500 - Lymphocyte separation medium.

Science.gov (United States)

2010-04-01

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

Cellular energy metabolism in T-lymphocytes.

Science.gov (United States)

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

2015-01-01

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

Kinetics of small lymphocytes in normal and nude mice after splenectomy

DEFF Research Database (Denmark)

Hougen, H P; Hansen, F; Jensen, E K

1977-01-01

Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...... thymic activity and diminished numbers of T lymphocytes in peripheral lymphoid tissues. The total number of cells in these tissues as well as the blast cell activity, were within normal limits. Bone marrow lymphocyte numbers and kinetics as well as blood lymphocyte levels in splenectomized and sham......-splenectomized normal animals were comparable. Blood lymphocyte numbers were at normal levels in splenectomized nude mice, in spite of reduced numbers of bone marrow and thoracic duct lymphocytes. It is suggested that increased number of newly-formed lymphocytes, found in lymph nodes and blood of splenectomized mice...

Acute Lymphocytic Leukemia

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

S. V. Khaidukov

2009-01-01

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

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

Lifescience Database Archive (English)

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

Application of rosula-formation tests for determining man lymphocyte radiosensitivity

International Nuclear Information System (INIS)

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

1982-01-01

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

Radioprotective effect of flavonoid quercetin on human lymphocytic cells

International Nuclear Information System (INIS)

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

2017-01-01

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

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: are they useful for predicting gestational diabetes mellitus during pregnancy?

Directory of Open Access Journals (Sweden)

Sargın MA

2016-04-01

Full Text Available Mehmet Akif Sargın, Murat Yassa, Bilge Dogan Taymur, Ayhan Celik, Emrah Ergun, Niyazi Tug Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey Objective: We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR could be utilized to screen for gestational diabetes mellitus (GDM.Subjects and methods: NLR and PLR were assessed by retrospective analysis of 762 healthy and pregnant women with GDM. The patients were stratified into four groups, as follows: GDM (n=144, impaired glucose tolerance (n=76, only screen positive (n=238, and control (n=304.Results: The leukocyte, neutrophil, and lymphocyte counts were significantly higher in the study groups compared with the control group (P=0.001; P<0.01. There were no statistically significant differences between the groups with respect to the NLR and PLR (P>0.05.Conclusion: We do not recommend that blood NLR and PLR can be used to screen for GDM. However, increase in the leukocyte count is an important marker for GDM as it provides evidence of subclinical inflammation. Keywords: inflammation, lymphocytes, neutrophils, platelets, pregnancy

Characterization of cat dander-specific T lymphocytes from atopic patients

NARCIS (Netherlands)

van Neerven, R. J.; van de Pol, M. M.; van Milligen, F. J.; Jansen, H. M.; Aalberse, R. C.; Kapsenberg, M. L.

1994-01-01

Fel d I, the major cat dander allergen, is recognized by serum IgE of more than 80% of all cat-allergic patients. Because IgE synthesis by B lymphocytes is under the control of T lymphocytes, we studied the specificity and lymphokine production profiles of cat dander-specific T lymphocytes.

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

International Nuclear Information System (INIS)

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

1992-07-01

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

Response of human lymphocytes to low gamma ray doses

International Nuclear Information System (INIS)

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

2001-01-01

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

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp

DEFF Research Database (Denmark)

Nielsen, Jeppe Sylvest; A, Larsson; Brix-Christensen, Vibeke

2005-01-01

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors...... hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis...... sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number...

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

OpenAIRE

van Attekum, Martijn HA; Eldering, Eric; Kater, Arnon P

2017-01-01

The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenv...

Cell kinetic and radiosensitivity of PHA stimulated goat lymphocytes

International Nuclear Information System (INIS)

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

1982-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

T gamma/delta lymphocytes in renal transplant recipients

NARCIS (Netherlands)

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

1992-01-01

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

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

Science.gov (United States)

2018-05-10

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

Is total lymphocyte count related to nutritional markers in hospitalized older adults?

Directory of Open Access Journals (Sweden)

Vânia Aparecida LEANDRO-MERHI

Full Text Available ABSTRACT BACKGROUND Older patients are commonly malnourished during hospital stay, and a high prevalence of malnutrition is found in hospitalized patients aged more than 65 years. OBJECTIVE To investigate whether total lymphocyte count is related to other nutritional markers in hospitalized older adults. METHODS Hospitalized older adults (N=131 were recruited for a cross-sectional study. Their nutritional status was assessed by the Nutritional Risk Screening (NRS, anthropometry, and total lymphocyte count. The statistical analyses included the chi-square test, Fisher's exact test, and Mann-Whitney test. Spearman's linear correlation coefficient determined whether total lymphocyte count was correlated with the nutritional markers. Multiple linear regression determined the parameters associated with lymphocyte count. The significance level was set at 5%. RESULTS According to the NRS, 41.2% of the patients were at nutritional risk, and 36% had mild or moderate depletion according to total lymphocyte count. Total lymphocyte count was weakly correlated with mid-upper arm circumference (r=0.20507; triceps skinfold thickness (r=0.29036, and length of hospital stay (r= -0.21518. Total lymphocyte count in different NRS categories differed significantly: older adults who were not at nutritional risk had higher mean and median total lymphocyte count ( P =0.0245. Multiple regression analysis showed that higher lymphocyte counts were associated with higher triceps skinfold thicknesses and no nutritional risk according to the NRS. CONCLUSION Total lymphocyte count was correlated with mid-upper arm circumference, triceps skinfold thickness, and nutritional risk according to the NRS. In multiple regression the combined factors that remained associated with lymphocyte count were NRS and triceps skinfold thickness. Therefore, total lymphocyte count may be considered a nutritional marker. Other studies should confirm these findings.

Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy

Directory of Open Access Journals (Sweden)

Fatih Mehmet Yazar

2015-11-01

Full Text Available Acute appendicitis (AA is not uncommon during pregnancy but can be difficult to diagnose. This study evaluated the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR in addition to conventional diagnostic indicators of the disease to diagnose AA during pregnancy. Age, gestational age, white blood cell (WBC count, Alvarado scores, C-reactive protein (CRP, lymphocyte count, NLR and PLR were compared among 28 pregnant women who underwent surgery for AA, 35 pregnant women wrongly suspected as having AA, 29 healthy pregnant women, and 30 nonpregnant healthy women. Mean WBC counts and CRP levels were higher in women with proven AA than in those of control groups (all p < 0.05. Among all the groups, the median NLR and PLR were significantly different in women with proven AA (all p < 0.05. Receiver operating characteristic analysis was used to determine cut-off values for WBC count, CRP, lymphocyte count, NLR and PLR, and multiple logistic regression analysis showed that NLR and PLR used with routine methods could diagnose AA with 90.5% accuracy. Used in addition to routine diagnostic methods, NLR and PLR increased the accuracy of the diagnosis of AA in pregnant women.

Nucleolar size in lymphocytes and haemocytes of different species

Directory of Open Access Journals (Sweden)

J Berger

2009-08-01

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

Analysis of cytotoxic effects of nickel on human blood lymphocytes.

Science.gov (United States)

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

2018-02-01

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

Changes in helper and suppressor T lymphocytes following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Newman, G.H.; Rees, G.J.G.; Jones, R.S.J.; Grove, E.A.; Preece, A.W.

1987-01-01

Changes in total lymphocyte, T lymphocyte, T helper and T suppressor lymphocyte numbers were studied in 22 patients with breast cancer before and after radiotherapy. T lymphocyte subsets were measured using monoclonal antibodies and fluorescence microscopy. After treatment the total lymphocyte count fell significantly and was still reduced 9 months later, but the proportion of cells labelled as T lymphocytes was unchanged during this period. The helper-suppressor ratio, which was within the normal range before radiotherapy, was significantly reduced at 3 months and 9 months after. Following treatment both T helper and T suppressor cell numbers were significantly reduced. T helper cell numbers remained reduced throughout the study period but T suppressor cell numbers showed a recovery to normal values 9 months after radiotherapy. (author)

Activation of human T lymphocytes by Leishmania lipophosphoglycan

DEFF Research Database (Denmark)

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

1991-01-01

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

Influence factors of human T lymphocyte co-stimulatory effect in vitro

International Nuclear Information System (INIS)

Zhou Jianhua; Su Liaoyuan; Tong Jian; Xue Lian

2000-01-01

Objective: Effects of CD3 McAb, CD28 McAb, PHA and low-dose γ-ray irradiation on T lymphocytes were investigated to explore factors of influencing T cell signals transduction. Method: Using CD3 McAb and CD28 McAb mimicking as the first and the second signals, and using PHA and low dose γ-rays irradiation as stimulatory factors in T cell activation, the influences of these factors and the two signals on human lymphocyte proliferation response were studied with 3 H-thymidine incorporation. Results: Lymphocyte proliferation response occurred when the two signals were treated co-stimulation or within certain intervals (within 40h). PHA and 10 cGy γ-rays irradiation can also activate lymphocytes to proliferate. However, each of the two signals alone did not activate lymphocytes to proliferate. Conclusion: CD3 McAb, CD28 McAb, PHA and low-dose γ-rays irradiation could stimulate T lymphocyte proliferation, which is an important aspect in cellular immune regulation

Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat

International Nuclear Information System (INIS)

Tanaka, S.; Sakai, A.

1979-01-01

The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulatng capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3 H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude

Atg5 Is Essential for the Development and Survival of Innate Lymphocytes

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Timothy E. O’Sullivan

2016-05-01

Full Text Available Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK cells and group 1, 2, and 3 innate ILCs. Although inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia.

Lymphocytic Panhypophysitis: Its Clinical Features in Japanese Cases

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Yoshiharu Wada

2011-01-01

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

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

International Nuclear Information System (INIS)

Benjamin, S.A.; Ferris, A.C.

1974-01-01

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

Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes

International Nuclear Information System (INIS)

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

1984-01-01

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

The Genotoxicity of Sodium Arsenite in Human Lymphocyte Culture

International Nuclear Information System (INIS)

El-Habit Ola, H.M.

1998-01-01

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

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

International Nuclear Information System (INIS)

Prusek, W.; Astaldi, G.

1979-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1979-01-01

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

Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

International Nuclear Information System (INIS)

Goodman, M.G.; Fidler, J.M.; Weigle, W.O.

1978-01-01

The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

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

DEFF Research Database (Denmark)

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

1986-01-01

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

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

DEFF Research Database (Denmark)

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

1986-01-01

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

In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

International Nuclear Information System (INIS)

Whitson, M.E.; Griffin, G.D.; Novelli, G.D.; Solomon, A.

1981-01-01

Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by 51 Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes

In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

Energy Technology Data Exchange (ETDEWEB)

Whitson, M.E. (Univ. of South Carolina, Columbia); Griffin, G.D.; Novelli, G.D.; Solomon, A.

1981-01-01

Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by /sup 51/Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes.

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Platz, P

1985-01-01

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50...

Leukemia -- Chronic T-Cell Lymphocytic

Science.gov (United States)

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

Telomerase levels control the lifespan of human T lymphocytes

NARCIS (Netherlands)

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

2003-01-01

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

The genotoxicity of sodium arsenite in human lymphocyte culture

International Nuclear Information System (INIS)

Elhabit, O.H.M.

1995-01-01

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

Radiosensitivities of sensitized lymphocytes

International Nuclear Information System (INIS)

Taniguchi, Kazuto

1979-01-01

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

Lymphocytic hypophysitis and hypothalamitis - a case report

International Nuclear Information System (INIS)

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

2006-01-01

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

Primary lymphocytic lymphoma of lacrimal gland.

Science.gov (United States)

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

2017-02-01

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

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

African Journals Online (AJOL)

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

Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

NARCIS (Netherlands)

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

1997-01-01

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

Lymphocyte mediators of delayed hypersensitivity; the early phase cells

Energy Technology Data Exchange (ETDEWEB)

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

1978-04-01

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

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

Science.gov (United States)

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

Lymphocyte colony forming units and its application to the study of radiosensitivity

International Nuclear Information System (INIS)

Ma Xiangrui; Wang Tao; Wang Hongyun

1991-07-01

Kinetics and radiosensitivity of human lymphocytes were studied by the techniques of monolayer agar culture and liquid culture in vitro. In the experiments of lymphocyte kinetics, PHA was designated as a motogen for T lymphocyte. LPS, MEBC and BSA were chosen as mitogens for B lymphocyte. The data from thses experiments showed that under the alone or combination stimulation of LPS, MRBC and BSA, B lymphocytes developed to form colonies in agar culture (0.3%) with the same manner. The stimulation of LPS to B lymphocytes was most significant. By the day 6 after seeding, the numbers of colonies in agar culture were maximal. Whereas the numbers decreased significantly by the day 8. The number of T lymphocyte colonies increased with culture time within 12 days. The peak of 3 H-TdR incorporation into T lymphocytes in liquid culture occured at 5th day after seeding. The data above-mentioned demonstrated that the kinetics of lymphocytes cultured in two kinds of environments were different. The studies of the radiosensitivity of T lymphocytes showed that the decreasing in the number of colonies and rate of 3 H-TdR incorporation varied in different dose ranges. In the range of 0∼1.0 Gy, r = -0.96, D 0 value was 1.71 Gy for TL-CFC in agar culture, r = -.96, D 0 value was 4.34 Gy for the proliferation T lymphocytes in liquid culture. In the range of 1.0∼6.0 Gy, r were -0.99 and -0.98, the D 0 were 5.88 and 7.36 Gy respectively. The declining tendency in colonies formed by BL-CFC was the same as that of TL-CFC, r = -0.97, for the range of 0∼1.0 Gy, r = -0.97, for the range of 1.0∼3.0, the D 0 values were 1.35 and 4.36 Gy respectively. The results from these experiments shown that the colony technique was a good method for the study in radiosensitivity

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

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

2018-03-01

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

T-dependence of human B lymphocyte proliferative response to mitogens.

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Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

In-vitro responses of T lymphocytes to poly(butylene succinate) based biomaterials.

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Toso, Montree; Patntirapong, Somying; Janvikul, Wanida; Singhatanadgit, Weerachai

2017-04-01

Polybutylene succinate (PBSu) and PBSu/β-tricalcium phosphate (TCP) composites are biocompatible and good candidates as bone graft materials. However, little is known about the responses of T lymphocytes to these biomaterials, which play an important role in the success of bone grafting. Activated T lymphocytes were cultured onto 32 mm diameter films (PBSu/TCP films), that had previously been placed in 6-well culture plates, for 8, 24 and 72 hours. A plastic-well culture plate was used as a control surface. The effects of PBSu-based biomaterials on T lymphocytes were examined by the using flow cytometry and reverse-transcription polymerase chain reaction. These biomaterials were non-toxic to T lymphocytes, allowing their normal DNA synthesis and activation. All materials induced only transient activation of T lymphocytes, which existed no longer than 72 hours. Proportions of four main CD4/CD8 T lymphocyte subpopulations were not affected by these biomaterials. Moreover, PBSu and PBSu/TCP significantly suppressed the expression of IL-1β and IL-6 genes by 15-35% and 21-26%, respectively. In contrast, a PBSu/TCP composite (at PBSu:TCP=60:40) significantly stimulated the expression of IL-10 and IL-13 genes by 17% and 19%, respectively. PBSu and PBSu/TCP composites were non-toxic to T lymphocytes and did not induce unfavorable responses of T lymphocytes. The tested biomaterials down-regulated key proinflammatory cytokine genes and up-regulated anti-inflammatory cytokine genes in T lymphocytes. These suggest that the biomaterials studied are good candidates as bone graft materials.

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

International Nuclear Information System (INIS)

Yamashita, Chiho; Satoh, Daigo; Yosue, Takashi

2001-01-01

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

Morphometric Characterization of Small Cell Lymphocytic Lymphoma

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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.

Genotoxic effects of borax on cultured lymphocytes.

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Pongsavee, Malinee

2009-03-01

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

Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

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Caroline Boda

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

Biometric indices of recirculating lymphocytes after acute and chronic gamma-irradiation

International Nuclear Information System (INIS)

Kalinin, E.V.

1978-01-01

The karyometry method was used to study the distribution of mature lymphocytes of lymphatic organs and peripheral blood among classes of nuclear volumes. Radiation injury was accompanied by a selection of populations of short-lived lymphocytes with very big nuclei the content of which was function of cumulative radiation dose. The number of small lymphocytes dependend on the phase of the radiation reaction

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation

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Yi Guo

2014-12-01

Full Text Available Aim: To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation (bAVM is not associated with iron deposition (indicator of micro-hemorrhage. Methods: Sections of unruptured, previously untreated bAVM specimens (n = 19 were stained immunohistochemically for T-lymphocytes (CD3 + , B-lymphocytes (CD20 + , plasma cells (CD138 + and macrophages (CD68 + . Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains. Superficial temporal arteries (STA were used as control. Results: Both T-lymphocytes and macrophages were present in unruptured, previously untreated bAVM specimens, whereas few B cells and plasma cells were detected. Iron deposition was detected in 8 specimens (42%; 95% confidence intervals = 20-67%. The samples with iron deposition tended to have more macrophages than those without (666 ± 313 vs. 478 ± 174 cells/mm 2 ; P = 0.11. T-cells were clustered on the luminal side of the endothelial surface, on the vessel-wall, and in the perivascular regions. There was no correlation between T-lymphocyte load and iron deposition (P = 0.88. No macrophages and lymphocytes were detected in STA controls. Conclusion: T-lymphocytes were present in bAVM specimens. Unlike macrophages, the load and location of T-lymphocytes were not associated with iron deposition, suggesting the possibility of an independent cell-mediated immunological mechanism in bAVM pathogenesis.

9 CFR 113.42 - Detection of lymphocytic choriomeningitis contamination.

Science.gov (United States)

2010-01-01

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

Intestinal T lymphocytes of different rat strains in immunotoxicity

NARCIS (Netherlands)

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

1999-01-01

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

Pathomorphology of spleen lymphocyte apoptosis in large dose 60Co γ-irradiated mice

International Nuclear Information System (INIS)

Gao Linlu; Cui Yufang; Yang Hong; Xia Guowei; Peng Ruiyun; Gao Yabing; Wang Dewen

2000-01-01

Objective: The aim of the authors was to investigate the pathomorphology changes of spleen lymphocyte apoptosis after 60 Co γ-irradiation. Methods: The mice were irradiated with 6, 9, 12, 15 and 20 Gy of 60 Co γ-rays. At different times after irradiation, the mice were sacrificed and the pathological changes of spleen lymphocyte were observed by light and transmission electron microscopies. Results: Spleen lymphocyte decreased evidently and the peak of apoptosis in spleen lymphocyte was dependent on radiation dose and the time after irradiation. Conclusion: After γ-irradiation with large doses, pathological changes of spleen lymphocyte apoptosis in mice can be divided into obviously different stages. The main causes of death of spleen lymphocytes are different in different dose groups

Influence of immunomodulators on the lymphokine secretion of irradiated lymphocytes

International Nuclear Information System (INIS)

Kowalczyk-Bronisz, S.H.

1986-01-01

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

CD4+ LYMPHOCYTES IMPROVE VENOUS BLOOD FLOW IN EXPERIMENTAL ARTERIOVENOUS FISTULAE

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

2015-01-01

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

Adaptive response induced by low concentrations of MMC in human peripheral lymphocytes

International Nuclear Information System (INIS)

Sun Shuqing; Wang Bin; Jiang Jie

1998-01-01

Samples of cultured human peripheral lymphocytes were pre-treated with mitomycin C (MMC) in concentrations of 0.01∼0.1 μg/mL at 34 h of incubation and then exposed to 1.5 Gy of X-rays. Chromosome aberrations, sister chromatid exchanges and micronuclei for these lymphocytes were observed. The results show that the chromosome aberration rates for lymphocytes pre-treated with MMC in concentrations of 0.5 and 0.075 μg/mL and the frequencies of sister chromatid exchanges for lymphocytes pre-treated with MMC in concentrations of 0.01 μg/mL were significantly lower than their own expected values but the rates of micronuclei for lymphocytes pre-treated with MMC in concentrations of 0.05, 0.075 and 0.1 μg/mL were significantly higher than the expected values. Such results suggest that for studying the cross resistance of lymphocytes to chemicals and ionizing radiation, inconsistent conclusions may be obtained if different endpoints are based on

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

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

2015-04-01

In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

African Journals Online (AJOL)

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

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

International Nuclear Information System (INIS)

Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

1987-01-01

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases

Fate of lymphocytes after withdrawal of tofacitinib treatment.

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

2014-01-01

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

Fate of lymphocytes after withdrawal of tofacitinib treatment.

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Elisa Piscianz

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

Lymphocytic Colitis: Pathologic predictors of response to therapy.

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Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

2018-02-13

While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

REACTIVITY OF BLOOD LYMPHOCYTES IN PULMONARY TUBERCULOSIS

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R. R. Khasanova

2009-01-01

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

CD4dullCD8bright double-positive T-lymphocytes have a phenotype of granzyme Bpos CD8pos memory T-lymphocytes

NARCIS (Netherlands)

Rentenaar, R. J.; Wever, P. C.; van Diepen, F. N.; Schellekens, P. T.; Wertheim, P. M.; ten Berge, I. J.

1999-01-01

BACKGROUND: T-lymphocytes that co-express CD4 and CD8 antigens may be found in small percentages in the peripheral blood of healthy individuals, and have a CD4brightCD8dull phenotype. CD4dullCD8bright T-lymphocytes have been found only in temporal association with some viral infections. METHODS:

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

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

2015-02-01

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

Stages of Chronic Lymphocytic Leukemia

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

Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

Energy Technology Data Exchange (ETDEWEB)

Astaldi, G [Blood Research Foundation Center, Tortona, Italy; Karanovic, D; Vettori, P P; Karanovic, J; Piletic, O

1974-01-01

The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

Lymphocytic hypophysitis: occurrence in two men.

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

1994-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Studies of lymphocyte growth and differentiation. Progress report, September 1, 1975--July 31, 1976

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Rubin, A.D.

1976-01-01

Studies were continued on ribonuclear protein synthesis and the assembly of ribosomes in resting and stimulated lymphocytes. We demonstrated the interdependency of protein synthesis and RNA synthesis in the formation and processing of nascent ribonuclear protein particles. We further explored lymphocyte nuclei in a cell-free system. By isolating lymphocyte chromatin we showed a direct effect of PHA on the ability of this nuclear structure to incorporate radioactivity into acid precipitable RNA. We returned to our previous studies on the delayed response of chronic lymphocytic leukemia (CLL) lymphocytes to PHA. We traced this alternate response identifying it as a characteristic of the CLL cell. The evidence questioned the generally accepted conclusion that CLL represents a B cell malignancy. We went on further to describe delayed reacting lymphocytes in the circulation of patients with nodular lymphoma and acute lymphoblastic leukemia (ALL). The ALL, unlike the lymphoma and CLL cells, showed a normal magnitude of response, even though it was delayed. We described the technique which might be employed as a diagnostic test for detecting abnormal lymphocytes in patients with lymphocytic lymphoma and leukemia and could help distinguish these diseases from benign lymphoid hyperplasia and other forms of non-lymphocytic leukemia.

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

Science.gov (United States)

Snider, D E; Parker, C W

1976-01-01

In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

DEFF Research Database (Denmark)

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

2001-01-01

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

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

International Nuclear Information System (INIS)

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

1977-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2001-03-01

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

Lymphocyte subsets and response to PHA among atomic bomb survivors

International Nuclear Information System (INIS)

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

1986-01-01

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

Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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Khadijeh Khosravi

2016-05-01

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

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

Science.gov (United States)

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

2009-06-01

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

Repair of single-strand breaks in normal and trisomic lymphocytes

International Nuclear Information System (INIS)

Leonard, J.C.; Merz, T.

1982-01-01

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

Latent childhood thyroid carcinoma in diffuse lymphocytic thyroiditis.

Science.gov (United States)

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

1983-07-01

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

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

International Nuclear Information System (INIS)

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

1980-01-01

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

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

Science.gov (United States)

Yang, Jie; Hu, Chongkang; Jiang, Xun

2016-09-01

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

Effect of low dose x-irradiation on alloantigen sensitized and unsensitized lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Dohi, Kiyohiko; Yahata, Hiroshi; Fukuda, Yasuhiko; Asahara, Toshimasa; Ono, Eiji; Ezaki, Haruo

1984-12-01

The effect of local graft irradiation on immune response in allograft in which acute rejection occurs was studied using an in vitro model. Unidirectional mixed lymphocyte culture (MLC) was used as the in vitro model of acute rejection. 150 and 300 rad x-irradiation suppressed mixed lymphocyte reaction (MLR) but did not cell-mediated-lympholysis (CML) of unsensitized lymphocytes. X-irradiated alloantigen sensitized cells (ASC) generated in 6-day MLC suppressed MLR and CML of unsensitized lymphocytes. Suppressive effects of x-irradiated ASC were of the same degree by x-irradiation doses of 150-500 rad. Suppressive effect of x-irradiation was maintained for only a short period after x-irradiation. Potential function of suppressor precursor cells among unsensitized lymphocytes was abolished by x-irradiation of 300 rad. (author).

Is the Oxidative DNA Damage Level of Human Lymphocyte Correlated with the Antioxidant Capacity of Serum or the Base Excision Repair Activity of Lymphocyte?

Directory of Open Access Journals (Sweden)

Yi-Chih Tsai

2013-01-01

Full Text Available A random screening of human blood samples from 24 individuals of nonsmoker was conducted to examine the correlation between the oxidative DNA damage level of lymphocytes and the antioxidant capacity of serum or the base excision repair (BER activity of lymphocytes. The oxidative DNA damage level was measured with comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated with a modified comet assay including nuclear extract of lymphocytes for enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent antioxidant capacity assay. We found that though the endogenous DNA oxidation levels varied among the individuals, each individual level appeared to be steady for at least 1 month. Our results indicate that the oxidative DNA damage level is insignificantly or weakly correlated with antioxidant capacity or BER activity, respectively. However, lymphocytes from carriers of Helicobacter pylori (HP or Hepatitis B virus (HBV tend to give higher levels of oxidative DNA damage (P<0.05. Though sera of this group of individuals show no particular tendency with reduced antioxidant capacity, the respective BER activities of lymphocytes are lower in average (P<0.05. Thus, reduction of repair activity may be associated with the genotoxic effect of HP or HBV infection.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

Science.gov (United States)

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

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

African Journals Online (AJOL)

McRoy

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

Production of C-reactive protein by human lymphocytes

International Nuclear Information System (INIS)

Kuta, A.E.; Baum, L.L.

1986-01-01

C-reactive protein (CRP) is a major acute phase serum protein in humans; it is detectable at very high concentrations during infection and tissue trauma. This protein is a pentame composed of five identical, 21,500 MW subunits. CRP is detectable on the surface of approximately 4% of normal peripheral blood lymphocytes (PBL). CRP binds its physiological ligands in a Ca ++ dependent manner; removal of Ca ++ does not alter the expression of CRP on the lymphocyte surface. Recently, investigators in this laboratory reported substantial inhibition of natural killer cell (NK) activity with anti-CRP antibodies. The following studies were undertaken to determine the origin of surface-CRP (S-CRP) found on normal PBL. Cells were incubated in methionine-free DMEM supplemented with 35 S-methionine. Cells were lysed and subjected to immunoprecipitation with anti-CRP and Staphylococcus aureus; immunoprecipitates were analyzed by SDS-PAGE and autoradiography. Data presented here suggested that lymphocytes, in particular, LGL produce small amounts of CRP and express it on their surface. Lymphocytes do not appear to secrete CRP since no CRP could be detected in culture supernatants. In addition, preliminary evidence indicates that peripheral blood monocytes produce no detectable CRP. Present studies utilizing Northern blot analysis are underway in order to detect CRP-mRNA

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.

Role of Circulating Lymphocytes in Patients with Sepsis

Directory of Open Access Journals (Sweden)

Raul de Pablo

2014-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

Energy Technology Data Exchange (ETDEWEB)

Astaldi, G. (Blood Research Foundation Center, Tortona, Italy); Karanovic, D.; Vettori, P.P.; Karanovic, J.; Piletic, O.

1974-01-01

The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

Kinetics of human lymphocyte division and chromosomal radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

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

1979-12-01

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

Human T Lymphocytes Are Permissive for Dengue Virus Replication.

Science.gov (United States)

Silveira, Guilherme F; Wowk, Pryscilla F; Cataneo, Allan H D; Dos Santos, Paula F; Delgobo, Murilo; Stimamiglio, Marco A; Lo Sarzi, Maria; Thomazelli, Ana Paula F S; Conchon-Costa, Ivete; Pavanelli, Wander R; Antonelli, Lis R V; Báfica, André; Mansur, Daniel S; Dos Santos, Claudia N Duarte; Bordignon, Juliano

2018-05-15

Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4 + and CD8 + T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4 + and CD8 + T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4 + but not CD8 + T cells after exposure to DV in vitro Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4 + and CD8 + T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infection in vitro and in vivo , suggesting that this cell population may be a viral reservoir during the acute phase of the disease. IMPORTANCE Infection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show

CHARACTERIZATION OF TWO MONOCLONAL ANTIBODIES WHICH RECOGNIZE DIFFERENT SUBPOPULATIONS OF CHICKEN T LYMPHOCYTES

OpenAIRE

KONDO, Takashi; HATTORI, Masakazu; KODAMA, Hiroshi; ONUMA, Misao; MIKAMI, Takeshi

1990-01-01

Distribution among peripheral T lymphocyte subpopulations and biochemical properties of the chicken lymphocyte surface antigens defined by monoclonal antibodies (mAbs) Lc-4 and Lc-6 were examined. Two-color immunofluorescence analysis revealed that Lc-4 and Lc-6 antigens were expressed on mutually exclusive subpopulations of peripheral T lymphocytes but not on B lymphocytes. Lc-4 mAb precipitated a polypeptide with apparent molecular mass of 35 and 65 kilodalton under reducing and non-reducin...

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

Science.gov (United States)

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

2006-07-01

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

Langerhans cells and subsets of lymphocytes in the nasal mucosa

DEFF Research Database (Denmark)

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

1991-01-01

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

B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice.

Science.gov (United States)

Charlton, B; Zhang, M D; Slattery, R M

2001-12-01

Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

Science.gov (United States)

Shi, Yufang

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

Radiosensitivity of human lymphocytes and thymocytes

International Nuclear Information System (INIS)

Kwan, D.K.; Norman, A.

1977-01-01

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

Differentiation of peripheral lymphocyte population in Pu-exposed beagle dogs

International Nuclear Information System (INIS)

Morris, J.E.

1977-01-01

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

Lymphocytes as a neural probe : potential for studying psychiatric disorders

NARCIS (Netherlands)

Gladkevich, A; Kauffman, HF; Korf, J

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

Assessment of in vitro radiosensitivity of human peripheral blood lymphocytes

International Nuclear Information System (INIS)

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

1980-01-01

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

Food allergens inducing a lymphocyte-mediated immunological reaction in canine atopic-like dermatitis

OpenAIRE

SUTO, Akemi; SUTO, Yukinori; ONOHARA, Nozomi; TOMIZAWA, Yu; YAMAMOTO-SUGAWARA, Yukiko; OKAYAMA, Taro; MASUDA, Kenichi

2014-01-01

Canine atopic-like dermatitis (ALD) is suspected to be associated with food allergies, particularly those mediated by lymphocytes. In this study, 54 cases were included as ALD dogs, based on the negative IgE test results. In the dogs, the percentage of activated cells in helper-T lymphocytes was measured by flow cytometry using cultured peripheral lymphocytes under food allergen stimulation. We observed that 49 of the 54 ALD dogs (90.7%) had positive lymphocyte reactions against one or more f...

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

Growth of human T lymphocyte colonies from whole blood: culture requirements and applications

International Nuclear Information System (INIS)

Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.

1982-01-01

Growth of human lymphocyte colonies from whole blood following stimulation with PHA, Con A, or PPD is described. Individual colony cells were identified as T lymphocytes on the basis of surface marker and enzyme cytochemical characterizations. Colony formation increased as a power function over a wide range of cell concentrations above a critical minimal concentration. The whole blood culture system eliminates possible selective effects of lymphocyte colony techniques utilizing gradient-enriched lymphocyte fractions and more closely approximates the in vivo milieu. The whole blood colony method is more sensitive for the detection of low-level radiation effects on lymphocytes than widely used tests that measure 3 H-thymidine incorporation. In preliminary studies, researchers used the whole blood method to determine the relative radiosensitivity of lymphocytes from humans with various hematopoietic disorders, and observed abnormalities in mitogen responsiveness and colony formation in some of the patient groups. This method has wide application for studies in cellular and clinical immunology

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

International Nuclear Information System (INIS)

Topliss, D.J.; Okita, N.; Lewis, M.; Row, V.V.; Volpe, R.

1981-01-01

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

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

Science.gov (United States)

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

2018-06-08

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

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

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Juliane Morando

2012-01-01

Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Increased ratio between anaerobic and aerobic metabolism in lymphocytes from hyperthyroid patients.

Science.gov (United States)

Valdemarsson, S; Monti, M

1994-03-01

While an increased oxygen consumption is accepted as one consequence of hyperthyroidism, only few data are available on the role of anaerobic processes for the increased metabolic activity in this disease. In this study we evaluated the relative importance of anaerobic and aerobic metabolism for the metabolic activity in lymphocytes from patients before and after treatment for hyperthyroidism. Total lymphocyte heat production rate (P), reflecting total cell metabolic activity, was determined in a plasma lymphocyte suspension using direct microcalorimetry. The contribution from aerobic metabolism (O2-P) was calculated from the product of the lymphocyte oxygen consumption rate and the enthalpy change for glucose combustion, and the anaerobic contribution as the difference between P and O2-P. The total lymphocyte heat production rate P was 3.37 +/- 0.25 (SEM) pW/cell (N = 11) before and 2.50 +/- 0.11 pW/cell (N = 10) after treatment for hyperthyroidism (p hyperthyroid state and to 73.7 +/- 3.2% after treatment (p metabolic activity demonstrated in lymphocytes from hyperthyroid patients cannot be explained by an increased oxygen-dependent consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

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

DEFF Research Database (Denmark)

Hokland, M; Hokland, P; Heron, I

1983-01-01

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

PHA-induced cytotoxicity of human lymphocytes against adherent hela-cells

NARCIS (Netherlands)

Huges-Law, G.; de Gast, G. C.; The, T. Hauw

The conditions for a phytohaemagglutinin(PHA)-induced cytotoxicity test of human peripheral blood lymphocytes were investigated. [3H]thymidine prelabelled HeLa cells were used as target cells. Stimulation with 10 μl PHA/ml during 24 h gave the best measure of lymphocyte cytotoxic capacity.

Radiochemical and immunohistochemical detection of low density lipoprotein surface binding by lymphocytes

International Nuclear Information System (INIS)

Melzner, I.; Hambitzer, R.; Haferkamp, O.

1983-01-01

Human peripheral blood lymphocytes bind and take up low density lipoprotein (LDL) by receptor-mediated endocytosis. The binding of LDL was determiend by incubation with 125 I-LDL and an immunohistochemical assay. By both techniques a diminished rate of binding was found when cells were freshly isolated from the blood, but increased 5 to 10 fold when lymphocytes were incubated in lipoprotein-deficient medium for 72 hours. In addition, it was shown immunohistochemically that only few ceels showed an LDL-dependent fluorescent labelling: approximately 5 to 10 % of the freshly isolated lymphocytes and 40 to 50 % of the cells incubated for 72 hours under lipoprotein-free conditions. The present data indicate that not only the high affinity LDL receptor described by Goldstein and Braun may be involved in the uptake of cholesterol by lymphocytes, but also other binding sites, which may have immunological function in some lymphocyte subpopulations. (author)

Dynanics of populations of T- and B-lymphocytes in the irradiated body

International Nuclear Information System (INIS)

Yarilin, A.A.

1978-01-01

On the basis of literary data analysis the estimation of lymphocyte radiosensitivity with the account of dividing this cell type into numerous varieties is given. Estimation results have shown that during in vitro irradiation at 1000 P dose rate in the first day 80 percent of blood B-cells and about 30 percent of T cells are killed. By the fourth day lymphocyte killing approaches maximum: B cells vanish practically completely, and T cells make up 6-8% of the initial content. The lymphocyte reduction greatly depends on an injury character. T and B lymphocyte reduction dynamics is in principle analogous except for some difference in reduction periods

Lymphocyte as a biological dosimeter : a different approach

International Nuclear Information System (INIS)

Madhvanath, U.

1974-01-01

Chromosome aberration frequency as a measure of radiation exposure in human blood lymphocytes following a short term culture is well known and the technique is in use at several laboratories in the world to determine accidental exposures. Results of an entirely different approach to arrive at the exposure is presented. Time course of interphase death of human peripheral blood lymphocytes was followed for 6 days after exposure to cobalt-60 gamma radiation. Trypan blue dye exclusion method was used for scoring viable cells. Survival curves at 5 days post irradiation were exponential and had two components: an initial sensitive component representing a major sub-population of lymphocytes with a mean lethal dose (DO) of 75 rads and the other an apparently more resistant population with a Do of about 300 rads. The initial part of the survival curve which spans to about 100 rads reaching a survival level of 15 percent, can be used to read off the extent of exposure in accident cases. Although 60 percent of the initial lymphocytes survive in the unexposed control cultures, the method is sensitive to exposures of the order of 20 rads and reproducible results have been obtained. The response is independent of dose-rate from 65 rads/min to 65 rads/hour. Other aspects of the dosimetry system such as the neutron response, in vitro and in vivo correlation are discussed. (author)

Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Science.gov (United States)

A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Monitoring of cardiac antirejection therapy with 111In lymphocytes

International Nuclear Information System (INIS)

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

1982-01-01

To determine whether lymphocytes labeled with 111 In permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with 111 In were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of 111 In lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with 111 In-labeled lymphocytes will permit noninvasive assessment of antirejection therapy

Spleen lymphocyte function modulated by a cocoa-enriched diet.

Science.gov (United States)

Ramiro-Puig, E; Pérez-Cano, F J; Ramírez-Santana, C; Castellote, C; Izquierdo-Pulido, M; Permanyer, J; Franch, A; Castell, M

2007-09-01

Previous studies have shown the down-regulating in vitro effect of cocoa flavonoids on lymphocyte and macrophage activation. In the present paper, we report the capacity of a long-term rich cocoa diet to modulate macrophage cytokine secretion and lymphocyte function in young rats. Weaned rats received natural cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for 3 weeks. Spleen immune function was then evaluated through the analysis of lymphocyte composition, their proliferative response and their ability to secrete cytokines and Ig. In addition, the status of activated peritoneal macrophages was established through tumour necrosis factor (TNF)-alpha secretion. The richest cocoa diet (10%) caused a reduction of TNF-alpha secretion by peritoneal macrophages showing anti-inflammatory activity. Similarly, although a 10% cocoa diet increased lymphocyte proliferation rate, it down-regulated T helper 2 (Th2)-related cytokines and decreased Ig secretion. These changes were accompanied by an increase in spleen B cell proportion and a decrease in Th cell percentage. In summary, these results demonstrate the functional activity of a cocoa-high dosage in down-regulating the immune response that might be beneficial in hypersensitivity and autoimmunity.

Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

DEFF Research Database (Denmark)

Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

2013-01-01

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

Bare lymphocyte syndrome: imaging findings in an adult

International Nuclear Information System (INIS)

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

2001-01-01

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

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

Science.gov (United States)

Tishevskaya, N V; Gevorkyan, N M; Kozlova, N I

2017-01-01

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma?

Directory of Open Access Journals (Sweden)

Tanoglu A

2014-03-01

Full Text Available Alpaslan Tanoglu,1 Ergenekon Karagoz,2 Nurettin Yiyit,3 Ufuk Berber4 1Department of Gastroenterology, 2Department of Infectious Diseases and Clinical Microbiology, 3Department of Thoracic Surgery, 4Department of Pathology, GATA Haydarpasa Training Hospital, Uskudar, TurkeyWe read with interest the recent article entitled "Combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma" by Feng et al.1 In their study, authors aimed to investigate the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Finally, they concluded that combination of NLR and PLR is a useful predictor of postoperative survival in patients with ESCC and combination of these parameters is superior to NLR or PLR as a predictive factor in patients with ESCC. We would like to thank the authors for their contribution.View original paper by Feng and colleagues.

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

DEFF Research Database (Denmark)

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

1977-01-01

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

Lymphocytic gastritis: a newly described entity: a retrospective endoscopic and histological study.

Science.gov (United States)

Haot, J; Hamichi, L; Wallez, L; Mainguet, P

1988-01-01

Lymphocytic gastritis is a histopathological entity characterised by the accumulation of small lymphocytes in the surface and foveolar epithelium. In order to investigate the correlation between endoscopy and histology in this condition, 192 observations selected on the basis of a presumed diagnosis of erosive or varioliform gastritis were reviewed. Ninety two instances corresponded to lymphocytic gastritis, while 100 did not show any particular microscopic feature and were labelled non-specific gastritis. There was a good correlation (48 of 58) between the diagnosis of the so-called varioliform gastritis and the histological evidence of lymphocytic gastritis. The correlation was even better when nodules, erosions, and enlarged folds were considered. Lymphocytic gastritis has a typical endoscopical appearance consisting of nodules, erosions, and large folds predominating in the gastric body. This contrasts with non-specific gastritis, which affects the antrum and produces erosions on a flat mucosa. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:3198002

Immunoregulatory and antioxidant performance of alpha-tocopherol and selenium on human lymphocytes.

Science.gov (United States)

Lee, Chung-Yung Jetty; Wan, Jennifer Man-Fan

2002-05-01

The role of alpha-tocopherol (alpha-toco) and selenium (Se) on human lymphocyte oxidative stress and T-cells proliferation were studied by flow cytometry. We measured the hydrogen peroxide and glutathione levels in cultured human T-lymphocytes and the proliferation of their subsets: T-helper/inducer, T-suppressor/cytotoxic, and natural killer and interleukin-2 receptors upon stimulation by the mitogens phytohemaglutinin (PHA) and lipopolysaccharide (LPS). The results indicate that early stimulation by mitogens is affected by the glutathione and hydrogen peroxide status of the T-lymphocytes. The addition of 100 microM or 500 microM alpha-toco or 0.5 microM Se alone shows weak antioxidant and immunostimulant properties. When combined, an enhanced antioxidant and immunoregulatory effect was observed. The present findings indicate that alpha-toco and Se have interactive effects as oxygen radical scavengers, thus promoting human lymphocyte response to antigens. This suggests that micronutrient status is an important factor in considering when interpreting the results of in vitro assays of lymphocyte function.

In vitro X-ray irradiation of human peripheral blood T lymphocytes enhances suppressor function

International Nuclear Information System (INIS)

Ogawa, H.; Tsunematsu, T.

1983-01-01

The effect of in vitro X-ray irradiation on human peripheral blood T lymphocytes was studied with regard to their suppressor activity related to the concanavalin A (Con A)-induced suppressor system. To generate suppressor T lymphocytes, purified human T lymphocytes were incubated for 3 days in the first culture, with or without Con A. These lymphocytes were irradiated with various doses of X-ray before, mid or after the culture. After doing a second culture for 6 days, the suppressive influence of these cells on T lymphocyte proliferation rates stimulated with allogeneic mononuclear cells, and B lymphocyte proliferation rates stimulated with pokeweed mitogen was measured. Irradiation of cultures to which Con A had not been added induced much the same level of suppressor activity as seen in the cultures with Con A. The suppressor activity gradually increased with time from the irradiation to the suppressor cell assay. Suppressor T lymphocytes were resistant to X-ray irradiation and independent of DNA synthesis. However, irradiation-induced enhancement was minimal in cultures incubated with con A, regardless of the irradiation time. (author)

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

Directory of Open Access Journals (Sweden)

Peng JH

2017-07-01

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

Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes

NARCIS (Netherlands)

Nijhara, Ruchika; van Hennik, Paula B.; Gignac, Michelle L.; Kruhlak, Michael J.; Hordijk, Peter L.; Delon, Jerome; Shaw, Stephen

2004-01-01

Lymphocytes circulate in the blood and upon chemokine activation rapidly bind, where needed, to microvasculature to mediate immune surveillance. Resorption of microvilli is an early morphological alteration induced by chemokines that facilitates lymphocyte emigration. However, the antecedent

Reactivity of eleven anti-human leucocyte monoclonal antibodies with lymphocytes from several domestic animals

DEFF Research Database (Denmark)

Aasted, Bent; Blixenkrone-Møller, Merete; Larsen, Else Bang

1988-01-01

Nine commercially available monoclonal antibodies and two monoclonal antibodies from The American Type Culture Collection, raised against various human leucocyte surface antigens, were tested on lymphocytes from cow, sheep, goat, swine, horse, cat, dog, mink, and rabbit as well as man. Four...... antibodies bound to lymphocytes from some of the animals. These were the antibodies against CD8 and CD4 antigen, the antibody to C3b-receptor, and the antibody to the HLA-DR antigen. The CD8 antigen-reactive antibody reacted with lymphocytes from mink, cat, dog, and sheep, while the CD4 antigen......-reactive antibody reacted with lymphocytes from mink. The anti-C3b-R antibody reacted with lymphocytes from horse, swine, dog, and cat, and the anti-HLA-DR reacted with lymphocytes from cow, goat, sheep, horse, dog, cat, and mink....

Lymphocytic gastritis: a newly described entity: a retrospective endoscopic and histological study.

OpenAIRE

Haot, J; Hamichi, L; Wallez, L; Mainguet, P

1988-01-01

Lymphocytic gastritis is a histopathological entity characterised by the accumulation of small lymphocytes in the surface and foveolar epithelium. In order to investigate the correlation between endoscopy and histology in this condition, 192 observations selected on the basis of a presumed diagnosis of erosive or varioliform gastritis were reviewed. Ninety two instances corresponded to lymphocytic gastritis, while 100 did not show any particular microscopic feature and were labelled non-speci...

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

Science.gov (United States)

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

2015-01-01

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

Radioprotective effect of antioxidants on human blood lymphocytes

International Nuclear Information System (INIS)

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

1991-09-01

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

Whole blood microculture assay of human lymphocyte function.

Science.gov (United States)

Pauly, J L; Han, T

1976-11-01

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

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

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Pushpa Ruwali

2018-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

Mathematical modeling reveals kinetics of lymphocyte recirculation in the whole organism.

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Vitaly V Ganusov

2014-05-01

Full Text Available The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours. Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs or the gut (mesenteric LNs or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

Lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis

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An-Ran Xu

2016-06-01

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

Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases

International Nuclear Information System (INIS)

Bittera, I.; Gyurkovits, K.; Falkay, G.; Eck, E.; Koltai, M.

1988-01-01

The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of 124 I-cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentivanyi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs

Normal lymphocyte immunophenotype in an elderly population

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Sâmia Macedo Queiroz Mota Castellão Tavares

2014-06-01

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

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

NARCIS (Netherlands)

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

2017-01-01

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

Effects of ketotifen on human lymphocytes in vitro and in vivo

NARCIS (Netherlands)

Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.

1993-01-01

The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

General Information about Chronic Lymphocytic Leukemia

Science.gov (United States)

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

T-lymphocyte subsets in West African children: impact of age, sex, and season

DEFF Research Database (Denmark)

Lisse, I M; Aaby, P; Whittle, H

1997-01-01

method to determine T-lymphocyte subsets. RESULTS: We found differences by age, sex, and season, whereas there were no significant differences by birth order, twinning, or ethnic group. The CD4+ percentage declined from birth to age 2 years, at which time it started to increase to higher levels at age 4......OBJECTIVE: There has been no reference material for T-lymphocyte subsets for normal children in developing countries. We therefore used T-lymphocyte subset determinations among children in three different studies in Guinea-Bissau to construct age-related reference material and to examine possible...... determinants of T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children younger than 6 years were included in the three community studies of T-lymphocyte subsets among twins and singletons, after measles infection and after measles immunization. We used the immunoalkaline phosphatase...

Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology

International Nuclear Information System (INIS)

Doherty, P.C.; Ceredig, R.; Allan, J.E.

1988-01-01

The Lyt2+ class I major histocompatibility complex (MHC)-restricted virus-immune T cells that induce murine lymphocytic choriomeningitis (LCM) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. The use of appropriate bone marrow radiation chimeras as LCM virus-infected, (immunosuppressed recipients for immune T-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic T lymphocytes (CTL) in spleen, they do not reconstitute the barrier to T-cell recruitment from blood to cerebrospinal fluid. This is true for chimeras made up to 8 months previously, even though the inflammatory monocytes and macrophages in such chimeras are all of donor bone marrow origin. Radiation-resistant cells in the spleens of these chimeras are also still able to further stimulate virus-immune CTL. There is no requirement for H-2 compatibility between virus-immune T lymphocytes and secondarily recruited monocytes, or T cells of an inappropriate specificity. The key event in LCM immunopathology may thus be localization of T cells to the antigen-presenting endothelium in brain, leading to the secretion of mediators that promote the nonspecific recruitment of monocytes and other T cells

Lymphocytic subsets and low-dose exposure

International Nuclear Information System (INIS)

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

1993-03-01

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

Survival and PHA-stimulation of #betta#-irradiated human peripheral blood T lymphocyte subpopulations

International Nuclear Information System (INIS)

Schwartz, J.L.; Darr, D.C.; Daulden, M.E.

1983-01-01

Human peripheral blood T lymphocyte subpopulations were identified and isolated on the basis of their ability to bind IgG (T-G), IgM (T-M), or neither immunoglobulin class (T-null). Lymphocytes were exposed to 0, 0.5, 1.0, 2.5 or 5.0 Gy of 60 Co #betta#-rays either as a T-cell suspension or as separated T cell subsets. Survival curves, determined 5 days after irradiation, revealed that each subset has radiosensitive and radioresistant portions, and that the T-G cell is the most sensitive subset. Mitotic indices of 48-h cultures showed that the response of unirradiated T lymphocytes to PHA varied greatly among the subsets, the highest indices being obtained for the T-M and the lowest for the T-G cells. With the possible exception of the T-G cells, the subsets are realtively resistant to mitotic effects of #betta#-rays. T-G cells suppress the PHA-induced mitotic response of the other T lymphocyte subsets, and this suppressor effect is radiosensitive, being abolished by 1.0 Gy. It is concluded that lymphocytes exposed to >= 1 Gy of #betta#-rays will have very few dividing B lymphocytes or T-G cells. This together with radiation-induced loss of T-G suppressor action means that the predominant lymphocyte types in mitosis after >=1 Gy are the radioresistant T-M and T-null cells. (orig.)

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-05-06

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

Stimulatory effect of low dose radionuclide on DNA synthesis and UDS in splenic lymphocytes

International Nuclear Information System (INIS)

Zhu Shoupeng; Yang Zhanshan

1999-12-01

To study the stimulatory effect on DNA synthesis and unscheduled DNA synthesis (UDS) in splenic lymphocytes induced by low dose enriched uranium 235 U. By using 3 H-TdR incorporation assay technique, the DNA replicative synthesis in PHA and LPS stimulated splenic lymphocytes was observed. By using DNA synthesis inhibitor such as hydroxyurea, the UV-induced unscheduled DNA synthesis in splenic lymphocytes occurred. When the injected low dose of enriched uranium 235 u was 0.1 μg/kg body weight, the transformation capacity was elevated for splenic T lymphocytes, simultaneously the stimulative index increased. The UDS of splenic lymphocytes induced by ultra-violate revealed a statistically significant increase by low dose of enriched uranium 235 U at the range of 0.1-20 μg/kg body weight. A stimulatory action of low dose enriched uranium 235 U on DNA replicative synthesis as well as on UV-induced UDS in splenic lymphocytes was detected

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

Energy Technology Data Exchange (ETDEWEB)

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

1975-05-01

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

Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

Science.gov (United States)

Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

1991-02-01

In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

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

International Nuclear Information System (INIS)

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

1980-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

International Nuclear Information System (INIS)

Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

1987-01-01

The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

Energy Technology Data Exchange (ETDEWEB)

Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

1987-11-01

The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

Intestinal intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti-tissue transglutaminase IgA for the diagnosis of celiac disease in lymphocytic enteritis.

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Fernando Fernández-Bañares

Full Text Available BACKGROUND & AIMS: An increase in CD3+TCRγδ+ and a decrease in CD3- intraepithelial lymphocytes (IEL is a characteristic flow cytometric pattern of celiac disease (CD with atrophy. The aim was to evaluate the usefulness of both CD IEL cytometric pattern and anti-TG2 IgA subepithelial deposit analysis (CD IF pattern for diagnosing lymphocytic enteritis due to CD. METHODS: Two-hundred and five patients (144 females who underwent duodenal biopsy for clinical suspicion of CD and positive celiac genetics were prospectively included. Fifty had villous atrophy, 70 lymphocytic enteritis, and 85 normal histology. Eight patients with non-celiac atrophy and 15 with lymphocytic enteritis secondary to Helicobacter pylori acted as control group. Duodenal biopsies were obtained to assess both CD IEL flow cytometric (complete or incomplete and IF patterns. RESULTS: Sensitivity of IF, and complete and incomplete cytometric patterns for CD diagnosis in patients with positive serology (Marsh 1+3 was 92%, 85 and 97% respectively, but only the complete cytometric pattern had 100% specificity. Twelve seropositive and 8 seronegative Marsh 1 patients had a CD diagnosis at inclusion or after gluten free-diet, respectively. CD cytometric pattern showed a better diagnostic performance than both IF pattern and serology for CD diagnosis in lymphocytic enteritis at baseline (95% vs 60% vs 60%, p = 0.039. CONCLUSIONS: Analysis of the IEL flow cytometric pattern is a fast, accurate method for identifying CD in the initial diagnostic biopsy of patients presenting with lymphocytic enteritis, even in seronegative patients, and seems to be better than anti-TG2 intestinal deposits.

Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

International Nuclear Information System (INIS)

Monobe, Manami

2002-01-01

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/μm 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)

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

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Xiao Xiao Tang

2010-08-01

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

Cosmic radiation induced chromosomal aberrations in human lymphocytes

International Nuclear Information System (INIS)

De Angelis, G.; Facius, R.; Reitz, G.

2003-01-01

Since decades, elevated frequencies of dicentric chromosomes (DIC) in human lymphocytes have successfully been used as a biological dosimeter in cases of acute, often accidental exposures to ionizing radiation. As long as duration and time lags after exposure are small compared to the lifetime of DIC, their frequencies can also be used to assess doses from protracted, chronic irradiation. E.g., within the substantial range of uncertainties, the frequencies of DIC observed in cosmonauts are compatible with the frequencies expected from doses of low and high LET radiation to which they were exposed in low earth orbit (LEO). On the other hand, frequencies of DIC detected in lymphocytes of civilian aviation crewmembers rarely correlate with the doses accumulated all along their professional career. For such long duration exposures with relatively low induction rates, the concomitant decay of DIC frequencies due to the removal during exposure of lymphocytes carrying DIC has to be taken into account. We present temporal profiles of frequencies of DIC during the exposure calculated with a model of exponential decay of DIC for some scenarios of chronic exposure to cosmic radiation. E.g., even after a 'heavily' shielded Mars mission, the expected frequencies of DIC in lymphocytes of astronauts will be 10 to 40 times higher than the terrestrial control levels. For air flight personnel we calculated the time profiles of frequencies of DIC in lymphocytes of a 'typical' pilot, a male cabin attendant and a female cabin attendant whose professional radiation exposures were recalculated for the actual flight routes flown during their entire flight career as recorded in detailed duty logs. These results demonstrate that experimental (epidemiological) studies concerning DIC in air or space flight personnel must explicitly take into consideration the temporal exposure profiles in the prospective study population and that the point in time at which blood samples are to be drawn must

Effects of exogenous and endogenous IL-2 on irradiated human peripheral blood lymphocytes

International Nuclear Information System (INIS)

Zhang Lansheng; Wang Ninghai; Luan Meiling

1993-08-01

Human peripheral blood lymphocytes were irradiated with 1 to 40 Gy of γ-ray, and then cultured with PHA to prepare supernatant containing IL-2 for observation of kinetics of endogenous IL-2 production and reversion of lymphocyte proliferation after adding a highly purified IL-2. IL-2 activity was determined by the ability to sustain IL-2 dependent cell line (CTLL), lymphocyte proliferation was determined by 3 H-TdR incorporation and T lymphocyte subsets by monoclonal antibodies. The experimental results showed that lymphocytes exposed to 60 Co synthesized less DNA than nonirradiated lymphocytes. The inhibitory effect can partially reversed by purified IL-2 at the γ-ray dose range of 1 to 10 Gy, while irradiation with 2.5 Gy resulted in a reduction of T cells and T subsets, and increase in CD + 4 /CD + 8 ratio. The ratio of subsets recovered after adding IL-2. The kinetics of IL-2 production showed that the endogenous IL-2 production rose markedly with increasing dose of irradiation at the range of 1 to 10 Gy, and the peak of IL-2 production was at the γ-ray dose of 10 Gy

A case report of gastric lymphocytic phlebitis, a rare mimic for malignancy

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Daniel L. Chan

Full Text Available Introduction: Lymphocytic phlebitis is a benign condition characterised by inflammation of the veins and rarely affects the gastrointestinal tract. Reported cases present as acute abdomen and involve the colon or small intestine. We report the fourth case of gastric lymphocytic phlebitis in the literature. Presentation of case: A 74-year-old female presented with eight weeks of abdominal pain. Findings at endoscopy were suggestive of a malignant ulcer on the greater curvature of antrum, while biopsies showed chronic gastritis without malignancy. Appearance at diagnostic laparoscopy was consistent with a malignant gastric ulcer with serosal changes. Due to persistent pain and the macroscopic appearance, she proceeded to have an open subtotal gastrectomy and D2 lymph node clearance. Despite macroscopic appearance, the microscopic examination demonstrated no malignancy, and was consistent with lymphocytic phlebitis with overlying ulceration. Discussion: This case was a mimic for gastric malignancy, with the benign diagnosis only being made after surgical resection. Gastric lymphocytic phlebitis is a rare differential diagnosis for gastric ulcers when biopsies are negative, although preoperative diagnosis is difficult given the lesions do not involve the mucosa. Conclusion: If clinical history and endoscopic findings are suspicious for malignancy, despite normal biopsies, an aggressive surgical resection remains reasonable given the rarity gastric lymphocytic phlebitis. Keywords: Lymphocytic phlebitis, Gastrectomy, Gastric vasculitis, Gastric ulcer, Case report

Cytogenetic analysis of the combined action of pesticides and radiation on human lymphocytes

International Nuclear Information System (INIS)

Ryabchenko, N.I.; Fesenko, Eh.V.; Antoshchina, M.M.

1995-01-01

The efficiency of the combined action of pesticides and irradiation at the G 0 stage was studied in cultured human lymphocytes. Carbophos (malathion) increased the yield of chromosome and chromatid fragments in irradiated lymphocytes. Herbicide 2,4-D (dichlorophenoxyacetic acid) raised lymphocyte radiosensitivity by increasing the yield of chromosome type aberrations, the radiosensitizing effect of the herbicide decreased as its concentration increased. 4 refs

Growing B Lymphocytes in a Three-Dimensional Culture System

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Wu, J. H. David; Bottaro, Andrea

2010-01-01

A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing

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

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

1999-08-01

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

Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

DEFF Research Database (Denmark)

Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

2016-01-01

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we...... prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD......57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present...

In vitro culture of skin-homing T lymphocytes from inflammatory skin diseases

DEFF Research Database (Denmark)

Bang, Karen; Lund, Marianne; Mogensen, Søren C

2005-01-01

We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors - interleukin-2 (IL-2) and IL-4 yielding approximately 100-160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests......, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P lymphocytes (P ... to immediate halt of proliferation. Blood mononuclear cells from patients and biopsies from healthy persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+, HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines from AD (P

Monitoring of genotoxic effects in lymphocytes of people exposed to pesticides

International Nuclear Information System (INIS)

Panek, A.; Marcos, R.; Cebulska-Wasilewska, A.

2002-01-01

The aim of this study was to assess the potential genotoxic risk of occupational exposure to pesticides. The DNA damage and the repair capacities of lymphocytes, in four groups of the people of various countries were assessed by the use of single cell gel electrophoresis (SCGE) also known as the Comet assay. The results from the analysis performed in the Spanish group are presented in this paper. Statistical analysis of the results shows a slightly higher level of the DNA damage in the untreated lymphocytes of donors from the group exposed to pesticides; however, only for donors below 30 years old are these differences significant (p<0.05). Although, comparison of the efficiency of the UV-C induced dimmers excision process did not indicate differences between exposed and referent groups, though lymphocytes for donors exposed to pesticides have shown a statistically lower repair rate (p<0.01) than lymphocytes from the unexposed group. (author)

Robot system for preparing lymphocyte chromosome

International Nuclear Information System (INIS)

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

1992-01-01

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

Lymphocytic hypophysitis masquerading as pituitary adenoma

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Rajneesh Mittal

2012-01-01

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

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

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

2014-01-01

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

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

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Cesar Miguel Momesso dos Santos

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

The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

International Nuclear Information System (INIS)

Yang Huibin

1989-01-01

The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

Cell proliferation and radiosensitivity of cow lymphocytes in culture

International Nuclear Information System (INIS)

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

1982-01-01

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

Characteristics of T lymphocyte subpopulations 

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Paulina Niedźwiedzka-Rystwej

2013-05-01

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

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

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Ertan Şahin

2018-04-01

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

Genetically enhanced T lymphocytes and the intensive care unit

Science.gov (United States)

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

2018-01-01

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

Psychological stress during exercise: lymphocyte subset redistribution in firefighters.

Science.gov (United States)

Huang, Chun-Jung; Webb, Heather E; Garten, Ryan S; Kamimori, Gary H; Acevedo, Edmund O

2010-10-05

The purpose of this study examined the changes in heart rate (HR), catecholamines (NE, EPI) and percentages of blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, CD3- CD56+ NK cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes [NK cells+T cells+B cells]) in firefighters exposed to a computerized firefighting strategies and tactics decision-making challenge while participating in moderate intensity exercise. Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and blood lymphocyte subsets following combined mental and physical challenge. Ten professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37min of cycle ergometry at 60% VO(2max) (exercise alone condition; EAC) and (2) 37min of cycle ergometry at 60% VO(2max) along with 20min of a computerized firefighting strategies and tactics decision-making challenge (firefighting strategies condition; FSC). FSC elicited significantly greater HR, NE, and EPI when compared to EAC. Both EAC and FSC elicited increases in CD3- CD56+ NK cells. The percentages of CD3+ T cells, CD3+CD4+ helper T cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes were lower immediately following both conditions. Following dual challenge NE AUC was negatively correlated with percentage of CD19+ B cells immediately post challenge, and HR was negatively associated with the percent change in the CD4/CD8 ratio from pre to post challenge. These elevations in NE and heart rate simultaneously in response to the dual challenge suggest greater sympathetic activation that in turn would possibly explain the alteration in the distribution of lymphocyte subsets. Published by Elsevier Inc.

Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

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Arshed Nazmi

2018-03-01

Full Text Available BackgroundPeriventricular leukomalacia (PVL is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured hemisphere compared to the contralateral (control, uninjured hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.

Decreased lymphocyte dopamine transporter in romantic lovers.

Science.gov (United States)

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

2017-06-01

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

Natural HIV-1 NEF accelerates virus replication in primary human lymphocytes

NARCIS (Netherlands)

de Ronde, A.; Klaver, B.; Keulen, W.; Smit, L.; Goudsmit, J.

1992-01-01

HIV-1 NEF genes were isolated directly from peripheral blood lymphocyte DNA of two HIV-1-infected individuals and cloned into an HXB-2-infectious molecular clone. The effect of NEF on virus production in T-cell lines and primary human lymphocytes was studied. Naturally occurring NEF accelerates

Assessment of radiation induced apoptosis in lymphocyte subpopulations

International Nuclear Information System (INIS)

Perez, M. del R.; Dubner, Diana L.; Michelin, Severino; Gisone, Pablo A.; Barboza, Marcos

2001-01-01

Apoptosis is the main form of radioinduced cell death. The lymphocytes, highly radiosensitive cells, dead in interphase by apoptosis even after very low doses. It has been demonstrated that the various peripheral blood lymphocyte (PBL) types display clear differences in their radiosensitivity . The purpose of this work was the characterization of radioinduced apoptosis in total PBL and in helper and cytotoxic T-lymphocytes. Blood samples were irradiated with a gamma source with doses between 0,5 and 4 Gy, dose-rate 0,8 Gy/min. Apoptosis was evaluated at different times post irradiation (p.i.) by conventional and fluorescence microscopy. Fragmentation of DNA was determined by electrophoresis in agarose gels. Apoptosis was quantified flow cytometrically by light scatter gram and determining the percent of fixed cells stained with propidium iodide that exhibited a reduced DNA content. FITC-labelled Annexin V was used to bind cell membrane phosphatidylserine which is aberrantly exposed during apoptosis. As an additional approach for the evaluation of apoptosis we measured the mitochondrial transmembrane potential by using the cationic dye 3,3 dihexyl oxacarbocyanine iodide (DiOC 6 ). Chromatin condensation and apoptotic bodies were microscopically observed and internucleosomal fragmentation was revealed in electrophoresis gels. Apoptotic cell fraction displayed a dose-dependent increase with a higher radiosensitivity for CD8 T-lymphocytes. These results suggest that quantification of PBL apoptosis could be an useful biological indicator in accidental overexposures and could also provide an useful predictive test for individual radiosensitivity. The higher radiosensitivity revealed by CD8 subset could allow a better discrimination of this phenomenon. (author)

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

International Nuclear Information System (INIS)

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

1988-07-01

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

Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.

Science.gov (United States)

Tokoyoda, Koji; Zehentmeier, Sandra; Hegazy, Ahmed N; Albrecht, Inka; Grün, Joachim R; Löhning, Max; Radbruch, Andreas

2009-05-01

CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.

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

Energy Technology Data Exchange (ETDEWEB)

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

1982-05-01

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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Late A-bomb effects on proliferation and mitotic inhibition of T- and B-lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Kazuo; Yoshimoto, Yasuhiko; Sasagawa, Sumiko; Sakatani, Tatsuichiro; Macchi, M; Fujikura, Toshio; Pirofsky, B; Hamada, Tadao

1984-11-01

In order to investigate late effects of ionization radiation and aging on T- and B-lymphocytes, mitotic ability of T- and B-lymphocytes in the peripheral blood of 266 A-bomb survivors was examined by determining the incorporation of (/sup 3/H)-thymidine. Phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were used as inducers. Furthermore, mitotic inhibition of lymphocytes induced by a lymphatic inhibitor which was in part prepared from ulex seed extracts (USE) was examined. A decreased reaction of peripheral lymphocytes to PHA was seen in men exposed to 100-199 rad; a decreased reaction to PWM was seen in women exposed to more than 200 rad. According to the age group at examination, these decreased reactions were remarkable in men aged 60 years or younger and women aged 60 years or older. Among men less than 60-year-old exposed to 100-199 rad, PWM-induced mitosis of lymphocytes tended to be inhibited remarkably by USE. These results suggest the involvement of late A-bomb effects in mitotic regulation of T- and B-lymphocytes of aged A-bomb survivors.

Effect of quercetin and 17-AAG on radiosensitivity of rat peripheral blood lymphocyte

International Nuclear Information System (INIS)

Chu Xuegang; Hong Chengjiao; Zhang Baoguo

2012-01-01

To investigate the effect of quercetin and 17-AAG on proliferation and on radiosensitivity of blood lymphocyte cells. CCK-8 assay is performed to evaluate the cytotoxicity of Quercetin on proliferation of blood lymphocyte cells. CCK-8 assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). CCK-8 results showed that the inhibition of Quercetin on the cells was the dose-dependent and time-dependent, and the results of assay showed the inhibition of 17-AAG on blood lymphocyte cells was the dose-dependent and time-dependent. The study showed that Quercetin and 17-AAG have no effect on the radiosensitivity of the blood lymphocyte cells. (authors)

Asymmetric T lymphocyte division in the initiation of adaptive immune responses.

Science.gov (United States)

Chang, John T; Palanivel, Vikram R; Kinjyo, Ichiko; Schambach, Felix; Intlekofer, Andrew M; Banerjee, Arnob; Longworth, Sarah A; Vinup, Kristine E; Mrass, Paul; Oliaro, Jane; Killeen, Nigel; Orange, Jordan S; Russell, Sarah M; Weninger, Wolfgang; Reiner, Steven L

2007-03-23

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

Chromosome aberrations frequencies in peripheral blood lymphocytes from patients with larynx cancer

International Nuclear Information System (INIS)

Lisowska, H.; Lankoff, A.; Banasik, A.; Padjas, A.; Wieczorek, A.; Kuszewski, T.; Gozdz, A.; Wojcik, A.

2005-01-01

There is data suggesting that the sensitivity to ionising radiation of peripheral blood lymphocytes of cancer patients is higher than in healthy donors. This effect is especially prominent when chromosomal aberrations induced in S/G2 phase of the cell cycle are analysed. The aim of our study was to investigate if the S/G2- aberration frequencies in lymphocytes of patients with larynx cancer were higher than in control individuals. In addition, the multiple fixation regimen was applied in lymphocytes of the cancer patients. The aim of this was to check if the aberration frequencies scored in cells harvested at one time point were representative for a larger fraction of the cell cycle. Peripheral blood of 40 patients was collected before the onset of radiotherapy, cultured and irradiated with Co-60 (2 Gy) after 67 hours of culture time. Irradiation was performed in the Swietokrzyskie Oncology Center. Chromosome specimens were prepared from cells fixed at three time points after irradiation: 5, 7 and 9 hours. Colcemide was always added for 2 hours before harvest. Lymphocytes of 40 healthy donors were cultured and irradiated in the same way like in the case of patients with cancer, however, they were only harvested at one time point (5 hours p.r.). No statistically significant differences in aberration frequencies were observed between lymphocytes harvested at the 3 time points. In both donor groups, individual differences in aberration frequencies were observed. Despite this, the aberration frequencies in lymphocytes of patients were in average higher than in the healthy donors. This suggests, that the radiation sensitivity of lymphocytes of patients with larynx cancer may be a marker of cancer predisposition. More patients must be analysed to confirm this hypothesis. (author)

Effects of cyclophosphamide on in vitro human lymphocyte culture and mitogenic stimulation

International Nuclear Information System (INIS)

Sharma, B.S.

1983-01-01

Cyclophosphamide (CY) has been reported to be inactive in vitro under certain conditions. In the present study, CY was tested for its ability to inhibit human lymphocyte proliferation and to modulate lymphocyte response to mitogens in vitro. The inhibition of or the increase in 3 H-thymidine incorporation in mitogen-stimulated and unstimulated lymphocytes by CY was used as a measure of CY activity in vitro. The results demonstrate that lymphocytes from 10 different persons had a mean decrease of 74% in 3 H-thymidine incorporation in the presence of CY (P less than 0.005). The effect was maximal at a concentration of 160 micrograms/ml. A mean inhibition of 35 and 55% was caused by 10 and 40 micrograms/ml concentrations of CY, respectively. CY also was able to reduce the number of viable cells during 5 days in culture and had a profound effect on mitogen stimulation of lymphocytes. In all cases, CY modulated the stimulation of lymphocytes by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) either by augmenting or suppressing the responses. At low concentrations (10 micrograms/ml) it augmented mitogenic stimulation by 46 to 281%. At higher concentrations (20 to 160 micrograms/ml), CY had a suppressive effect with a maximum suppression of 99%. The CY-induced immunomodulation is perhaps caused by its action on the regulatory T cells. When tested in vitro, CY had inhibitory activity on T cells

T lymphocyte migration: an action movie starring the actin and associated actors

Directory of Open Access Journals (Sweden)

Loïc eDupré

2015-11-01

Full Text Available The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

T Lymphocyte Migration: An Action Movie Starring the Actin and Associated Actors.

Science.gov (United States)

Dupré, Loïc; Houmadi, Raïssa; Tang, Catherine; Rey-Barroso, Javier

2015-01-01

The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers, and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is a key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.

OpenAIRE

Kanaly, S T; Hines, S A; Palmer, G H

1993-01-01

Pulmonary clearance of Rhodococcus equi requires functional T lymphocytes. In this study, CD8+ T-lymphocyte-deficient transgenic mice cleared virulent R. equi from the lungs while infection in CD4+ T-lymphocyte-deficient transgenic mice persisted. Although both CD4+ and CD8+ T cells function early in pulmonary defense against R. equi, clearance is dependent on CD4+ T lymphocytes.

Stimulating effects of vitamin A on PHA- and LPS-activated lymphocytes

International Nuclear Information System (INIS)

Liu Fengju; Su Liaoyuan

1993-03-01

A method of 3 H-TdR incorporation in lymphocytes activated by PHA was applied. The incubation with vitamin A at a concentration of 5 μg/ml for 16 hours was followed by the incorporation, the counts per minute (cpm) of radioactivity in lymphocytes increased significantly. When the concentration was greater than 25 μg/ml or the incubation at concentration of 10 μg/ml for 72 hours, the incorporation value of 3 H-TdR was remarkably decreased. The lymphocytes irradiated by 60 Co gamma rays at different doses were incubated in vitro with vitamin A of 5 μg/ml concentration for 16 hours, the cpm from 3 H-TdR incorporation in DNA was higher than that in control group with no vitamin A. Tests on 10 cancer patients showed that after one course of treatment with radiotherapy (75 ∼ 184 Gy), the incorporation value of 3 H-TdR was decreased significantly. After adding more 5 μg/ml concentration of vitamin A, the incorporation value of 3 H-TdR was remarkably greater than in the control group. These results indicated that vitamin A at adequate level is able to enhance the effect of transformation of PHA-activated lymphocytes, but the incorporation in LPS-activated B lymphocytes enhanced by vitamin A was not observed

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

Science.gov (United States)

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

1988-01-01

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

Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

KAUST Repository

Hill-Cawthorne, Grant A.

2011-11-05

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

Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

KAUST Repository

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

2011-01-01

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

Adherence of murine lymphocytes to high endothelial venules in vitro and its radiation effect

Energy Technology Data Exchange (ETDEWEB)

Lixin, Liu; Zijun, Mao; Zhiwei, Yin [Suzhou Medical Coll., JS (China). Dept. of Pathophysiology

1991-02-01

Using the assay of specific adhesion of lymphocytes to high endothelial venules (HEV) on cryostat sections of mesenteric lymph nodes (MLN), the effects of different doses (0, 1, 2, 4, 8 Gy) of {sup 60}Co {gamma}-ray irradiation of murine MLN lymphocytes in vitro on adhesion to normal HEV was observed. The results showed that in the irradiated murine MLN lymphocytes the ability to adhere to HEV of normal MLN was reduced. Statistical significance was revealed at 2, 4, 8 Gy irradiations. This results suggests that irradiation can inhibit the specific recognition and adhesion of lymphocytes to HEV to a certain extent.

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

International Nuclear Information System (INIS)

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

1980-01-01

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

A technique for separation of canine lymphocytes and their use in the lymphocytotoxic, blastogenic, and rosette assys.

Science.gov (United States)

Whitacre, C C; Lang, R W

1975-01-01

When the techniques established for preparing lymphocytes from human blood were applied to canine blood, the resulting preparations were contaminated with significant numbers of other blood cells. A three-step technique is described here for the separation of canine lymphocytes from blood which eliminates most granulocytes, platelets, and erythrocytes. Defibrinated blood is incubated with iron particles to allow phagocytosis by granulocytes. When mixed with Plasmagel, erythrocytes and iron-containing granulocytes sediment rapidly, leaving a lymphocyte-rich supernate plasma which is recovered and banded by centrifugation on a Ficoll-Hypaque gradient. Any erythrocytes remaining in the lymphocyte suspension aspirated from the gradient are eliminated by hypotonic lysis and centrifugation. The resulting preparation, representing 30 per cent recovery of the circulating lymphocytes, contained 85 to 94 per cent lymphocytes with a cell viability of 99 per cent. The functional capacity of the lymphocyte preparation was tested in three assays: 1) lymphoblastic transformation using phytohemagglutinin and pokeweed mitogen, 2) E rosette formation with human erythrocytes showed a mean 5 per cent rosette forming lymphocytes, 3) antibody-mediated lymphocytotoxicity using a canine anti-lymphocyte serum showed titers reproducible within one tube dilution.

Structural features of blood lymphocytes according to data of atomic force microscopy in alloxan induced diabetic rats

Science.gov (United States)

Stolbovskaya, Olga V.; Khayrullin, Radik M.; Kostishko, Boris B.; Bakhtiyarov, Rinat I.

2018-04-01

Structural changes in blood lymphocytes during the development of alloxan induced diabetes in rats were revealed. The changes were characterized by decreased volume, surface area, flatness coefficient of cells in comparison with normal lymphocytes. A consistent increase in the Young's modulus of rat lymphocytes during the development of diabetes in comparison with the Young's modulus of normal lymphocytes has been established, which indicates a decrease of the elastic-viscous properties of the cell membrane, changes in the molecular structure of its and in the organization of the lymphocyte cytoskeleton. It was found that during the development of induced diabetes the roughness and adhesiveness of the cytoplasmic membrane of blood lymphocytes decrease.

Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic epidermal necrolysis

DEFF Research Database (Denmark)

Hagdrup, H; Tønnesen, E; Clemmensen, O

1992-01-01

We examined the blood lymphocyte function and phenotypic pattern in a patient with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface markers, natural killer cell activity and mitogen-induced lymphocyte transformation. Our results point to temporary immunosuppression...... as evidenced by lymphopenia with a large "null cell" population, reduced natural killer cell activity, and impaired lymphocyte response to mitogens....

Food allergens inducing a lymphocyte-mediated immunological reaction in canine atopic-like dermatitis.

Science.gov (United States)

Suto, Akemi; Suto, Yukinori; Onohara, Nozomi; Tomizawa, Yu; Yamamoto-Sugawara, Yukiko; Okayama, Taro; Masuda, Kenichi

2015-02-01

Canine atopic-like dermatitis (ALD) is suspected to be associated with food allergies, particularly those mediated by lymphocytes. In this study, 54 cases were included as ALD dogs, based on the negative IgE test results. In the dogs, the percentage of activated cells in helper-T lymphocytes was measured by flow cytometry using cultured peripheral lymphocytes under food allergen stimulation. We observed that 49 of the 54 ALD dogs (90.7%) had positive lymphocyte reactions against one or more food allergens. The most common food allergen was soybean, showing positive results in 21 dogs (42.9%), while the allergen to cause the lowest number of reactions was catfish (only 5 dogs, 10.2%). These results may be useful in considering elimination diets for ALD dogs.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis.

Science.gov (United States)

Tang, Haowen; Lu, Wenping; Li, Bingmin; Li, Chonghui; Xu, Yinzhe; Dong, Jiahong

2017-05-30

Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.

In vitro exposure to X-radiation of stimulated and non-stimulated human B lymphocytes and T lymphocytes. In vitro Roentgenbestrahlung stimulierter und unstimulierter menschlicher B- und T-Lymphozyten

Energy Technology Data Exchange (ETDEWEB)

Krystossek, H.

1986-09-25

The sensitivity of human type B and type T lymphocytes to 130 kV X-radiation was investigated in vitro. The degree to which 3H thymidine was incorporated into the DNA of these cells was taken as a measure of cellular viability. The results led to the conclusion that the in vitro reactions to X-rays following stimulation and radiation are considerably more pronounced in human B lymphocytes than in human T lymphocytes. The rapid radiation-induced lessening of thymidine incorporation into stimulated B lymphocytes was interpreted as a sign that cellular decay occurred during the interphase. The relative increases in the thymidine incorporation rates seen following radiation of T cells in the presence of hydroxyurea or caffeinemust, however, not be mistaken for an augmentation of resistance that was brought about by these inhibitors. The latter effect is believed to be rather due to an overreaction of the repair mechanisms of DNA which is characterised by short chains.

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

NARCIS (Netherlands)

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

2015-01-01

In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the

THE CHANGES IN SEMEN LYMPHOCYTE SUBPOPULATION’S RATIO IN MEN INFERTILITY

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A. V. Semenov

2007-01-01

Full Text Available Abstract. The aim of present study was to investigate the ratios of semen lymphocyte subpopulations in males with infertility. Twenty-six men (20 to 45 years old suffering from different genital diseases (chronic prostatitis, idiopathic varicocoele, testicular atrophy were enrolled into the study. Six healthy age-matched normozoospermic male volunteers with normal fertility comprised a control group. Lymphocyte phenotyping was performed by flow cytometric technique. The patients with pathospermia showed increased numbers of CD25+ lymphocytes (p < 0.05, and unchanged levels of CD95+ cells, thus leading to increased CD25+/CD95+ ratio. In the patients with normozoospermia, the value of this index was 0.94±0.18. Increase of this parameter to > 1.2, as well as its reduction to < 0.7 was associated with sterility. We suggest that suppressed apoptosis of activated lymphocytes in semen may be potentially dangerous to spermatogenesis, since both immune response and associated inflammatory reactions can cause nonspecific lesions of surrounding tissues, and induction of pathospermia.

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

International Nuclear Information System (INIS)

Yachnin, S.; Lester, E.P.

1979-01-01

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

Human mixed lymphocyte cultures. Evaluation of microculture technique utilizing the multiple automated sample harvester (MASH)

Science.gov (United States)

Thurman, G. B.; Strong, D. M.; Ahmed, A.; Green, S. S.; Sell, K. W.; Hartzman, R. J.; Bach, F. H.

1973-01-01

Use of lymphocyte cultures for in vitro studies such as pretransplant histocompatibility testing has established the need for standardization of this technique. A microculture technique has been developed that has facilitated the culturing of lymphocytes and increased the quantity of cultures feasible, while lowering the variation between replicate samples. Cultures were prepared for determination of tritiated thymidine incorporation using a Multiple Automated Sample Harvester (MASH). Using this system, the parameters that influence the in vitro responsiveness of human lymphocytes to allogeneic lymphocytes have been investigated. PMID:4271568

Micronuclei in lymphocytes from currently active uranium miners

International Nuclear Information System (INIS)

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

2012-01-01

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

The comparison of radiosensitivity of human lymphocytes stimulated with PHA Con A and PWM

International Nuclear Information System (INIS)

Geng Yongzhi; Su Liaoyuan

1989-11-01

The transformation, DNA strand breaks and its repair ability in human peripheral blood lymphocytes stimulated with PHA, Con A and PWM were respectively assessed following exposure to 60 Co gamma rays by 3 H-thymidine uptake and hydroxylapatite chromatography. It was showed the transformation of lymphocytes stimulated with PHA, Con A and PWM were suppressed by gamma rays and the dose-effect curves were biphase within the range of 0∼8 Gy. The lymphocytes stimulated with PWM was the most resistant to gamma rays. The extent of DNA strand breaks in lymphocytes induced by gamma rays was linearly related to the dose within the range of 0∼30 Gy and was identical in three kinds of lymphocytes. After post-irradiation incubation of 37 deg C, the DNA strand breaks could be repaired incompletely and after maxium repair the strand breaks were observed again. The repair ratio of strand breaks in the lymphocytes stimulated with PWM was the highest in the cells with three mitogens. The results showed that the difference of radiation effect on the transformation is probably related to the repair ability of DNA strand breaks

Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes.

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Allison Choyce

Full Text Available Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16 E7 oncoprotein under a keratin 14 promoter (K14E7 mice display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes to premalignant skin.

Elevated Neutrophil Lymphocyte Ratio in Recurrent Optic Neuritis

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Hande Guclu

2015-01-01

Full Text Available Purpose. To demonstrate the relation between optic neuritis (ON and systemic inflammation markers as neutrophil lymphocyte ratio (N/L ratio, platelet count, mean platelet volume (MPV, and red cell distribution width (RDW and furthermore to evaluate the utilization of these markers to predict the frequency of the ON episodes. Methods. Forty-two patients with acute ON and forty healthy subjects were enrolled into the study. The medical records were reviewed for age, sex, hemoglobin (Hb, Haematocrit (Htc, RDW, platelet count, MPV, white blood cell count (WBC, neutrophil and lymphocyte count, and neutrophil lymphocyte ratio (N/L ratio. Results. The mean N/L ratio, platelet counts, and RDW were significantly higher in ON group (p=0.000, p=0.048, and p=0.002. There was a significant relation between N/L ratio and number of episodes (r=0.492, p=0.001. There was a statistically significant difference for MPV between one episode group and recurrent ON group (p=0.035. Conclusions. Simple and inexpensive laboratory methods could help us show systemic inflammation and monitor ON patients. Higher N/L ratio can be a useful marker for predicting recurrent attacks.

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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Mark Bustoros

2018-04-01

Full Text Available BackgroundPrimary extranodal marginal zone lymphoma (MZL of the dura is a rare neoplastic entity in the central nervous system (CNS.MethodsWe used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma (SLL.ResultsWe identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes.ConclusionPrimary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Operation of the Ca-dependent K(Rb)-transport in human lymphocytes

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Szasz, I.; Sarkadi, B.; Gardos, G. (Orszagos Haematologiai es Vertranszfuzios Intezet, Budapest (Hungary))

1982-01-01

The transport pathways of the plasma membrane of human lymphocytes were studied based on /sup 86/Rb and /sup 45/Ca fluxes. Net Ca-uptake increases K(Rb)-permeability (Gardos-effect) and the membrane potential increases due to the subsequent K-efflux, enabling further Ca-uptake. The possible role of the above effects during lymphocyte stimulation is discussed.

Induction of mitotic micronuclei by X-ray contrast media in human peripheral lymphocytes

International Nuclear Information System (INIS)

Parvez, Z.; Moncada, R.; Kormano, M.; Satokari, K.; Eklund, R.

1987-01-01

In vitro and in vivo cytogenetic effects of X-ray contrast media (CM) were determined by scoring micronuclei (MN) in 72-h cultures of human peripheral lymphocytes. Both ionic (sodium meglumine diatrizoate, methylglucamine diatrizoate, and sodium meglumine ioxaglate and nonionic CM (iosimide, iopromide, iohexol and iotrolan) were able to induce MN in lymphocytes. Based upon their calculated percent probabilities for MN induction, these agents could be ranked in their decreasing order of probability, as iosimide > sodium meglumine ioxaglate > iohexol > sodium meglumine diatrizoate > iopromide > methylglucamine diatrizoate > iotrolan. Stepwise logistic regression analysis of the data indicated that the frequency of MN in CM-exposed lymphocyte cultures was significantly higher than the frequency of MN in control cultures (P < 0.001). In clinical studies where 14 patients were injected with an ionic CM methylglucamine diatrizoate, lymphocyte cultures from 10 patients showed higher frequencies of MN. The differences between pre- and post-CM counts of MN were significant in a Mann-Whitney U test (P < 0.05). The effect of X-irradiation on MN formation in lymphocytes was separately determined and was found to be insignificant. These results indicate that irrespective of ionic and osmolality differences, X-ray contrast agents are capable of producing chromosomal damage in peripheral lymphocytes. Further studies are required to establish molecular mechanisms in the observed cytogenetic effects of CM in cell cultures. (Auth.)

Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes

International Nuclear Information System (INIS)

Lucas, J.N.; Hill, F.; Burk, C.; Straume, T.; Swansbury, G.; Clutterbuck, R.

1994-01-01

The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukaemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure pre-cancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of ∼ 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer in such patients. (Author)

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

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Dimitrios K. Manatakis

2018-01-01

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

Labeling with indium-111 has detrimental effects on human lymphocytes: concise communication

NARCIS (Netherlands)

ten Berge, R. J.; Natarajan, A. T.; Hardeman, M. R.; van Royen, E. A.; Schellekens, P. T.

1983-01-01

When lymphocytes from human peripheral blood were labeled with In-111 oxinate, several of their properties appeared to be affected. The spontaneous release of the radionuclide was found to be relatively high. Labeled lymphocytes showed a decreased proliferative capacity, dependent on the dose of the

Pattern of CD4 T‑lymphocyte Values in Cancer Patients on Cytotoxic ...

African Journals Online (AJOL)

Background: Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated ...

Acute lymphocytic leukaemia in children in the Netherlands

International Nuclear Information System (INIS)

Does-van den Berg, A. van der.

1980-01-01

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

Impaired T-lymphocyte colony formation by cord blood mononuclear cells

International Nuclear Information System (INIS)

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

1982-01-01

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

Response of human and rabbit lymphocytes to low doses of X-rays

International Nuclear Information System (INIS)

Fabry, L.

1982-01-01

The response of human and rabbit lymphocytes to low doses of X-rays was studied by the yields of dicentrics in first division metaphases. For both species, the dose-response curve was best fitted to the linear-quadratic model with a linear component predominating up to 67 and 42 rad respectively for man and rabbit. A calibration curve (5-400 rad) was obtained by combining the present results on man with previous data at higher doses. On the other hand, it appears that, at low doses, the radiosentivity of human lymphocytes is significantly higher than that of rabbit lymphocytes [fr

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

Science.gov (United States)

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

2012-02-01

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

Homing pattern of indium-111 T-lymphocytes in normal and tumor bearing rats

International Nuclear Information System (INIS)

Kasi, L.P.; Glenn, H.J.; Mehta, K.; Teckemeyer, I.C.; Wong, W.; Haynie, T.P.

1985-01-01

T-lymphocytes play an important role in tumor immunology and possess cytotoxic capabilities. Purified T-lymphocytes were obtained by incubating mononuclear cells separated from peripheral blood of Fisher 344 rats in a nylon wool column at 37 0 C. The non-adherent T-lymphocytes which were eluted from the column had > 95% viability. About 1 x 10/sup 7/ purified T-lymphocytes were labeled with 30 μCi In-111 oxine (Labeling yield: 75 +-5%, viability >95%). The function of the labeled cells as estimated by their graft versus host reaction ability remained unaltered. To evaluate the distribution pattern, 1 x 10/sup 6/ In-111 T-lymphocytes (per 100g wt) were injected via tail vein in normal and in transplanted (right flank) solid hepatoma bearing Fisher 344 rats, and the percent uptake of activity of the total injected dose per organ and per gm tissue was estimated at 2, 24 and 48 hours post injection. In normal rats maximum uptakes were in the liver (24%-33%) with increasing uptakes in the spleen (6.8%-11%) and minimum uptakes in the kidneys, lungs, muscles, and blood from 2 to 48 hours after injection. The uptake pattern in tumor bearing rats were significantly different during the same time period: lower in the liver (17%-19%) and a decrease in the spleen (9%-0.4%). All other tissues displayed similar uptake patterns as in normal animals. Maximum tumor:muscle ratio (18.4) was found at 48 hours post injection. Further studies are indicated for the possible use of In-111 T-lymphocytes in T-lymphocyte disorders, inflammations, and as an additional tool in the diagnosis of tumors

A case report of gastric lymphocytic phlebitis, a rare mimic for malignancy.

Science.gov (United States)

Chan, Daniel L; Ravindran, Praveen; Chua, Dorothy; Smith, Jason D; Wong, King S; Ghusn, Michael A

2017-01-01

Lymphocytic phlebitis is a benign condition characterised by inflammation of the veins and rarely affects the gastrointestinal tract. Reported cases present as acute abdomen and involve the colon or small intestine. We report the fourth case of gastric lymphocytic phlebitis in the literature. A 74-year-old female presented with eight weeks of abdominal pain. Findings at endoscopy were suggestive of a malignant ulcer on the greater curvature of antrum, while biopsies showed chronic gastritis without malignancy. Appearance at diagnostic laparoscopy was consistent with a malignant gastric ulcer with serosal changes. Due to persistent pain and the macroscopic appearance, she proceeded to have an open subtotal gastrectomy and D2 lymph node clearance. Despite macroscopic appearance, the microscopic examination demonstrated no malignancy, and was consistent with lymphocytic phlebitis with overlying ulceration. This case was a mimic for gastric malignancy, with the benign diagnosis only being made after surgical resection. Gastric lymphocytic phlebitis is a rare differential diagnosis for gastric ulcers when biopsies are negative, although preoperative diagnosis is difficult given the lesions do not involve the mucosa. If clinical history and endoscopic findings are suspicious for malignancy, despite normal biopsies, an aggressive surgical resection remains reasonable given the rarity gastric lymphocytic phlebitis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Low in vitro response to PPD and PHA in lymphocytes from BCG-induced pleurisy in guinea pigs

International Nuclear Information System (INIS)

Widstroem, O.; Nilsson, B.S.

1982-01-01

In order to study any correlation between functional properties of lymphocytes in BCG-induced pleural exudation and the development of the pleurisy a previously described experimental model was used. This model with a duration of effusion of more than 17 days has characteristic stages. From the third day and onwards there are lymphocytes in sufficient amount for in vitro cultures. Proliferation of lymphocytes from the fluid was measured as uptake of 14 C-thymidine. The response of the lymphocytes to PPD tuberculin and to phytohemagglutinin (PHA) was studied, and their spontaneous activity was measured. Comparisons were made with lymphocytes from regional lymph nodes. Pleural lymphocytes sampled on the third post-induction day did not respond to PPD or PHA stimulation. In later stages, pleural lymphocytes were stimulated by PPD to approximately the same degree as the lymph node lymphocytes. The response to PHA was weak at all stages of pleurisy, though in later stages there were some cases with high values. Variations in activation ability, related to disease staging, were demonstrated. However, low activities, and variability of the responces, without concomitant variations in disease, speak against a connection between the course of disease and functional status of the lymphocytes as measured in this study. (authors)

Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies.

Science.gov (United States)

Zhao, Zhe; Zhao, Xinrui; Lu, Jingjing; Xue, Jing; Liu, Peishu; Mao, Hongluan

2018-04-01

The systemic inflammatory response markers have been reported to be associated with the prognosis of various cancers. We conducted this meta-analysis of retrospective studies to evaluate and identify the prognostic impact of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on ovarian cancer. PubMed, EMBASE, and China National Knowledge Infrastructure databases were included to search for eligible studies. The following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma", "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and "ovary tumor". The random-effects model was chosen to estimate the pooled HR with 95% CI. Heterogeneity between studies was assessed by Higgins I 2 value. The stability and heterogeneity of studies were analyzed by sensitivity analysis. Publication bias was examined by Egger's test and Begg's test with the funnel plots. 13 studies consisting of 3467 patients were considered for meta-analysis. We found that the high NLR had a poor prognostic impact on OS and PFS in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI 1.48-2.12, respectively. Similarly, the results showed the high PLR adversely affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48 and HR 1.85, 95% CI 1.53-2.25, respectively. In conclusion, we found that both NLR and PLR had an unfavorable impact on PFS and OS of patients with ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective prognostic predictors of ovarian cancer.

Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors

International Nuclear Information System (INIS)

Abbas, A.K.; Haber, S.; Rock, K.L.

1985-01-01

Studies were designed to examine the ability of hapten-binding murine B lymphocytes to present hapten-protein conjugates to protein antigen-specific, Ia-restricted T cell hybridomas. BALB/c B cells specific for TNP or FITC presented hapten-modified proteins (TNP-G1 phi, TNP-OVA, or FITC-OVA) to the relevant T cell hybridomas at concentrations below 0.1 microgram/ml. Effective presentation of the same antigens by B lymphocyte-depleted splenocytes, and of unmodified proteins by either hapten-binding B cells or Ig spleen cells, required about 10(3)-to 10(4)-fold higher concentrations of antigen. The use of two different haptens and two carrier proteins showed that this extremely efficient presentation of antigen was highly specific, with hapten specificity being a property of the B cells and carrier specificity of the responding T cells. The presentation of hapten-proteins by hapten-binding B lymphocytes was radiosensitive and was not affected by the depletion of plastic-adherent cells, suggesting that conventional APCs (macrophages or dendritic cells) are not required in this phenomenon. Antigen-pulsing and antibody-blocking experiments showed that this hapten-specific antigen presentation required initial binding of antigen to surface Ig receptors. Moreover, linked recognition of hapten and carrier determinants was required, but these recognition events could be temporally separated. Finally, an antigen-processing step was found to be necessary, and this step was disrupted by ionizing radiation. These data suggest a role for B cell surface Ig in providing a specific high-affinity receptor to allow efficient uptake or focusing of antigen for its subsequent processing and presentation to T lymphocytes

Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

Directory of Open Access Journals (Sweden)

Lardon Filip

2010-04-01

Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

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

DEFF Research Database (Denmark)

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

1997-01-01

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

Study of the radioprotective effect of flavonoid quercetin on human lymphocytes

International Nuclear Information System (INIS)

Siqueira, Williams Nascimento de

2013-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

Allergic contact dermatitis: A commentary on the relationship between T lymphocytes and skin sensitising potency

International Nuclear Information System (INIS)

Kimber, Ian; Maxwell, Gavin; Gilmour, Nicky; Dearman, Rebecca J.; Friedmann, Peter S.; Martin, Stefan F.

2012-01-01

T lymphocytes mediate skin sensitisation and allergic contact dermatitis. Not unexpectedly, therefore, there is considerable interest in the use of T lymphocyte-based assays as alternative strategies for the identification of skin sensitising chemicals. However, in addition to accurate identification of hazards the development of effective risk assessments requires that information is available about the relative skin sensitising potency of contact allergens. The purpose of this article is to consider the relationships that exist between the characteristics of T lymphocyte responses to contact allergens and the effectiveness/potency of sensitisation. We propose that there are 3 aspects of T lymphocyte responses that have the potential to impact on the potency of sensitisation. These are: (a) the magnitude of response, and in particular the vigour and duration of proliferation and the clonal expansion of allergen-reactive T lymphocytes, (b) the quality of response, including the balance achieved between effector and regulatory cells, and (c) the breadth of response and the clonal diversity of T lymphocyte responses. A case is made that there may be opportunities to exploit an understanding of T lymphocyte responses to contact allergens to develop novel paradigms for predicting skin sensitising potency and new approaches to risk assessment.

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

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

2017-12-11

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

Comparison of two different techniques on the human lymphocytes morphology and sensitivity to gamma radiation

International Nuclear Information System (INIS)

Kol, R.

1985-02-01

The lymphocytes in the peripheral blood are divided into two main subclasses: T cells and B cells. These differ from each other in function and in their sensitivity to radiation. The effort to study which group is more sensitive to radiation has resulted in many contradictory results. In the present study we examined whether the methods that are used to separate the lymphocytes from the whole blood, before their separation into subclasses, have an effect on the cells and whether this might contribute to the contradictory results. Blood samples were taken from several normal donors and each sample was devided into two fractions. Lymphocytes in each fraction were separated by one of the two following methods: a) sedimentation of erythrocytes by gravitation; b) separation on Ficoll-Paque density gradient. For cells obtained by these two methods, the ultrastructure was examined by electron microscopy and their ability to incorporate radioactive thymidine was measured. Samples separated on Ficoll-Paque showed a subpopulation with morphological changes similar to those occuring in lymphocytes undergoing stimulation. Unstimulated cells separated on Ficoll-Paque showed greater sensitivity to radiation. The effect of gamma radiation on the capability of lymphocytes to undergo transformation in response to three mitogens; PHA, PWM and Con A was examined. Different mitogens stimulate different lymphocytes subpopulations. There was no difference between the two separation methods regarding the sensitivity to gamma radiation of stimulation by PAH and PWM. The transformation by Con A of lymphocytes separated on Ficoll-Paque was more radiosensitive. This could indicate that the separation by Ficoll-Paque density gradient causes a selective depletion of T lymphocytes that react with Con A and are considered more radioresistant. The use of different methods for separating lymphocytes from whole blood- each has a different influence on the cells- can contribute to contradictory

Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

DEFF Research Database (Denmark)

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

2014-01-01

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

Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

Directory of Open Access Journals (Sweden)

Jayesh H. Prajapati

2014-01-01

Full Text Available Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR and neutrophil-lymphocyte ratio (NLR with high density lipoprotein (HDL cholesterol levels in coronary artery disease (CAD patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P=0.008 and NLR (P=0.009; however no significant relationship was obtained with HDL and isolated platelet (P=0.488, neutrophil (P=0.407, and lymphocyte (P=0.952 counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024 and NLR (P=0.03 were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P=0.01 and NLR (6.33 versus 5.10; P=0.01 were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007 and NLR (P=0.001 were inversely associated with HDL, whereas in older population only NLR (P=0.05 had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Subpopulation of lymphocytes in patients with cancer of the head and neck

International Nuclear Information System (INIS)

Yoshida, Atsuhiro; Tomita, Kinai; Toda, Norikazu; Sekine, Kiyoshi; Mizugoe, Takanori

1978-01-01

On 31 patients with cancer of the head and neck, lymphocyte count and T- and B-cell levels were determined, and their changes following radiotherapy and the effect of picibanil on their changes were examined. 1) Lymphocyte count and T-cell count decreased remarkably following radiotherapy. B-cell count changed a little. Changes in lymphocyte count seemed chiefly to be due to changes in T-cell. 2) At 3 weeks after radiotherapy, lymphocyte count and T-cell count remained to be low in the patients who were not given picibanil, but those counts tended to increase in the patients who were given picibanil. The effect of picibanil was statistically significant in the experienced cases except those of maxillary cancer. 3) At 3 weeks after radiotherapy, T-cell count was significantly low in those who were not given picibanil and had unfavourable prognosis. 4) With 5 times repeated intramuscular injections of picibanil (0.2 KE), T-cell % and T-cell count increased in some cases. (Ueda, J.)

Imaging Polarized Secretory Traffic at the Immune Synapse in Living T Lymphocytes.

Science.gov (United States)

Calvo, Víctor; Izquierdo, Manuel

2018-01-01

Immune synapse (IS) formation by T lymphocytes constitutes a crucial event involved in antigen-specific, cellular and humoral immune responses. After IS formation by T lymphocytes and antigen-presenting cells, the convergence of secretory vesicles toward the microtubule-organizing center (MTOC) and MTOC polarization to the IS are involved in polarized secretion at the synaptic cleft. This specialized mechanism appears to specifically provide the immune system with a fine strategy to increase the efficiency of crucial secretory effector functions of T lymphocytes, while minimizing non-specific, cytokine-mediated stimulation of bystander cells, target cell killing and activation-induced cell death. The molecular bases involved in the polarized secretory traffic toward the IS in T lymphocytes have been the focus of interest, thus different models and several imaging strategies have been developed to gain insights into the mechanisms governing directional secretory traffic. In this review, we deal with the most widely used, state-of-the-art approaches to address the molecular mechanisms underlying this crucial, immune secretory response.

β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

International Nuclear Information System (INIS)

Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

1987-01-01

Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

International Nuclear Information System (INIS)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

1986-01-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using 5 H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function

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.)

Effects of mercury on the proliferation of human peripheral lymphocytes in vitro

International Nuclear Information System (INIS)

Piwecka, K.; Poniedzialek, B.; Rzymski, P.; Karczewski, J.; Zurawski, J.; Wiktorowicz, K.

2011-01-01

Our project aimed to investigate the effects of mercury on the proliferation of human peripheral lymphocytes in vitro. The lymphocytes were isolated from the blood collected from healthy donors at Regionalne Centrum Krwiodawstwa i Krwiolecznictwa in Poznan, Poland. For the purpose of cell culture, the lymphocyte suspension (25 · 10 4 cells/ml) in Eagle's medium supplemented with 10% fetal calf serum was prepared. Phytohaemagglutinin-L (PHA-L) was used in a concentration of 2.5 mg/ml to stimulate cell proliferation. Mercuric chloride (HgCl 2 ) in four different concentrations (1 μM, 10 μM, 50 μM, 100 μM) and [3H]-thymidine were added after 48 hours of incubation and the cell culture was continued for the next 24 hours. The rate of lymphocyte proliferation was measured by [3H]-thymidine incorporation method with a liquid scintillation counter. Results indicate that higher concentrations of mercury (50 μM, 100 μM) inhibit the [3H]-thymidine incorporation of human peripheral lymphocytes in vitro. The incorporation was lower than the control sample by 65% at a concentration of 50 μM, while at a concentration of 100 μM it fell to virtually zero. Moreover, the phase of lymphocyte proliferation cycle affected by mercuric chloride was also investigated. For this purpose HgCl 2 in 2 concentrations (10 μM, 50 μM) was added to the cell culture in 4 different time points: at the start of the cell culture and after 4, 24, and 48 hours of incubation. After 48 hours, [3H]-thymidine was added and the cell culture was continued for an additional 24 hours. The rate of cell proliferation was estimated by [3H]-thymidine incorporation using a liquid scintillation counter. The inhibition effect was observed in samples with metal added at the start of the cell culture and after 4 h of incubation, i.e. at the initial phase of the lymphocyte proliferation cycle. (authors)

Damage of chromosoms under irradiation of human blood lymphocytes and development of bystander effect.

Science.gov (United States)

Shemetun, O V

2016-12-01

the research the distribution of radiation induced damages among chromosomes and their bands in irra diated in vitro human blood lymphocytes and in unirradiated bystander cells.Material and methods of research: cultivation of human peripheral blood lymphocytes by semi micromethod D.A. Hungerford, modeling of radiation induced bystander effect in mixed cultures consisting of irradiated in vitro and non irradiated blood lymphocytes from persons of different gender, GTG staining of metaphase chromosomes and their cytogenetic analysis. Break points in chromosomes under the formation of aberrations were identified in exposed in vitro human peripheral blood lymphocytes in doses 0.25 Gy (95 breaks in 1248 cells) and 1.0 Gy (227 breaks in 726 cells) and in non irradiated bystander cells under their joint cultivation with irradiated in vitro human lymphocytes (51 breaks in 1137 cells at irradiation of adjacent populations of lymphocytes in dose 0.25 Gy and 75 breaks in 1321 cells at irradiation of adjacent population of lymphocytes in a dose 1.0 Gy). The distribution of injuries among the chromo somes and their bands was investigated. in radiation exposed in vitro human peripheral blood lymphocytes as well as in bystander cells the fre quency of damaged bands and number of breaks which localized in them exceeded the control value (p chromosomes were damaged according to their relative length. Location of bands with increasing number of breaks coincided with the «hot spots» of chromosome damage following irradiation and fragile sites. More sensitive to damage were G negative euchromatin chromosome bands, in which were localized 82 88 % breaks. Damageability of telomeric regions in the irradiated cells had no significant difference from the control, while in bystander cells was lower than control value (p < 0.05). O. V. Shemetun.

Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

African Journals Online (AJOL)

2018-02-07

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

Increased 22Na+-influx in lymphocytes from offspring of essential hypertensive patients

DEFF Research Database (Denmark)

Nielsen, J R; Pedersen, K E; Klitgaard, N A

1989-01-01

Lymphocytes were used as a cellular model for the in vitro measurements of 22Na+-influx during sodium pump inhibition by ouabain. The measurements were made using lymphocytes from young men at increased risk of developing essential hypertension in order to assess any changes and to analyse whether...

Canine lymphocyte activating factor (LAF)

International Nuclear Information System (INIS)

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

1979-01-01

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

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

Science.gov (United States)

Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

2015-07-01

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

Lymphocyte mobilization by dextran sulfate in beagles

International Nuclear Information System (INIS)

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

1978-01-01

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

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

Science.gov (United States)

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

2011-01-01

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

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

Science.gov (United States)

Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Bone marrow-derived T lymphocytes responsible for allograft rejection

International Nuclear Information System (INIS)

Senjanovic, M.; Marusic, M.

1984-01-01

Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

Association between neutrophil/lymphocyte ratio and coronary collateral circulation

Directory of Open Access Journals (Sweden)

Mustafa Oylumlu

2012-03-01

Full Text Available Objectives: To investigate relation between neutrophil/lymphocyte ratio and coronary collateral flow.Material and methods: Eighty-two patients admittedDicle University Medical Faculty Hospital Cardiology Departmentwith diagnosis of coronary artery disease anddetected significant stenosis or occlusion at least one ofthe coronary arteries, were included to study. Age, sex,presence of diabetes mellitus and hypertension, acute/stable coronary disease, body mass index, neutrophil/lymphocyte ratio, white blood count, Rentrop scores andnumber of diseased vessel were recorded.Results: Well-developed coronary collateral circulationwas found in 33 of the patients. Forty-nine patients hadpoor coronary collateral circulation. Mean age, sex, bodymass index, presence of diabetes mellitus and hypertensionwere similar in two groups. Mean neutrophil/lymphocyteratio was lower in well-developed coronary collateralcirculation group than poor coronary collateral circulationgroup, but there was no significant differences (2.78 vs2.89, p=0.12.Conclusions: There was no association between neutron/hil lymphocyte ratio and coronary collateral circulationaccording to our data. J Clin Exp Invest 2012; 3(1:29-32

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

Science.gov (United States)

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

2011-12-01

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

The essential role of chemokines in the selective regulation of lymphocyte homing.

Science.gov (United States)

Bono, María Rosa; Elgueta, Raúl; Sauma, Daniela; Pino, Karina; Osorio, Fabiola; Michea, Paula; Fierro, Alberto; Rosemblatt, Mario

2007-01-01

Knowledge of lymphocyte migration has become a major issue in our understanding of acquired immunity. The selective migration of naïve, effector, memory and regulatory T-cells is a multiple step process regulated by a specific arrangement of cytokines, chemokines and adhesion receptors that guide these cells to specific locations. Recent research has outlined two major pathways of lymphocyte trafficking under homeostatic and inflammatory conditions, one concerning tropism to cutaneous tissue and a second one related to mucosal-associated sites. In this article we will outline our present understanding of the role of cytokines and chemokines as regulators of lymphocyte migration through tissues.

Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis

Science.gov (United States)

Calder, Elizabeth A.; McLeman, Dena; Irvine, W. J.

1973-01-01

Lymphocytes from healthy donors were incubated with serum samples from nine patients with Hashimoto thyroiditis and subsequently shown to be cytotoxic to chicken red blood cells (Ch. RBC) coated with thyroglobulin. Target cell death was estimated using a standard 51Cr release assay system. Lymphocytes pre-incubated with Hashimoto serum caused a mean% 51Cr release of 13·11±2·83 (SEM) from thyroglobulin-coated Ch. RBC and a mean% 51Cr release of 1·22±0·65 from uncoated Ch. RBC. Untreated lymphocytes caused no significant isotope release from either uncoated or thyroglobulin coated target cells. PMID:4800956

Reference ranges for lymphocyte subsets in healthy adult male Oman is

International Nuclear Information System (INIS)

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

2008-01-01

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

Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

Directory of Open Access Journals (Sweden)

Frederick Wasinski

2014-01-01

Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

Combined effects of γ-ray radiation and high atmospheric pressure on peripheral blood lymphocytes

International Nuclear Information System (INIS)

Zhu Bingchai; Lu Jiaben; Wang Zongwu; Chen Tiehe

1989-01-01

The combined effects of γ-ray radiation and high atmospheric pressure on chromosome aberration, micronucleus and transformation frequency in peripheral blood lymphocytes have been studied. The results indicated that there were no significant influence for effects of high atmospheric pressure on chromosome aberrations, transformation frequency in peripheral blood lymphocytes induced γ-ray radiation, and that high atmospheric pressure increased effect of micronucleus in human peripheral blood lymphocytes in vitro induced γ-ray radiation

UDS in lymphocytes of occupationally radiation exposed persons

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.

1982-01-01

To determine a possible effect of low dose radiation on DNA repair processes, peripheral lymphocytes of mine workers exposed to 222 Rn in the thermal gallery of Badgastein (Austria) and employees of the Austrian Research Centre Seibersdorf, exposed to varying doses of gamma radiation, were investigated. The capacity for unscheduled DNA synthesis (UDS) induced by in vitro UV irradiation was measured by autoradiography of isolated lymphocytes of exposed persons and unexposed controls. In all 222 Rn-exposed mine workers a significant increase of UDS above control values could be observed. Gamma irradiation 31 mrad had a significant effect on UDS, indicating a stimulation of DNA repair capability by chronic low dose exposure. (Author)

Cellular immune therapy for chronic lymphocytic leukemia

NARCIS (Netherlands)

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

2007-01-01

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

Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ. Medical Center, Maywood, IL (United States); Chang-Liu, Chin-Mei [Argonne National Lab., IL (United States); Chung, Jen; Libertin, C.R. [Loyola Univ. Medical Center, Maywood, IL (United States)

1993-09-01

Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.

DNA metabolism in peripheral lymphocytes of UV-B wholebody irradiated men

International Nuclear Information System (INIS)

Klein, W.; Kocsis, F.; Altmann, H.

1983-02-01

Healthy probands were UV-B irradiated and different times after the treatment blood was taken and lymphocytes were isolated. Semiconservative DNA-synthesis was enhanced after 4 in vivo expositions. DNA repair replication in lymphocytes after in vitro UV-C damage was initially increased in UV-B wholebody irradiated people. With nucleoidsedimentation DNA strand breaks after in vivo UV-B irradiation were detected. (Author) [de

Survival of human lymphocytes after exposure to densely ionizing radiations

International Nuclear Information System (INIS)

Madhvanath, U.; Raju, M.R.; Kelly, L.S.

1976-01-01

Interphase death of human blood lymphocytes cultured in vitro was studied after exposure to 60 Co gamma rays and to accelerated ions of 1 H, 4 He, 7 Li, 11 B, 12 C, 20 Ne, 40 Ar, and π - meson beam under aerobic conditions. Exposures were also conducted under hypoxic conditions with 60 Co gamma rays, 4 He, 7 Li, and 12 C ion beams. Time course of interphase death was followed for 6 days after irradiation. Percent survivals were determined by using the trypan blue exclusion method. Survival curves at 5 days postirradiation were exponential for all radiations studied. These observations indicate that the production of interphase death of lymphocytes by densely ionizing radiations follows a pattern similar to that observed with colony-forming mammalian cells. However, the reproductive capacity of the latter cells is impaired with maximum effectiveness at energy densities associated with 220 keV/μm for the beam conditions used in this investigation. The much lower energy densities required to kill a lymphocyte suggest that a sensitive structure other than DNA may be responsible for the production of lymphocyte death, perhaps the membranes. The calculated inactivation cross sections for high-LET radiations above 650 keV/μm yielded values larger than the actual cell dimensions. It appears that contributions from delta rays become appreciable in this system at these LET's

Lymphocytic infiltration of bladder after local cellular immunotherapy.

Science.gov (United States)

Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

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

Directory of Open Access Journals (Sweden)

J Scott Hale

2010-04-01

Full Text Available Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development.Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development.Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-15

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

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

Science.gov (United States)

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

2016-12-01

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

DNA repair deficiency in lymphocytes from patients with actinic keratosis

International Nuclear Information System (INIS)

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

1978-01-01

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

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

Science.gov (United States)

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

2013-06-01

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

Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

International Nuclear Information System (INIS)

Streeter, P.R.

1985-01-01

Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

Cytokine gene expression of peripheral blood lymphocytes ...

African Journals Online (AJOL)

STORAGESEVER

2009-03-20

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

Differentiation of human lymphocytes into nuclear vlimata by meiosis. The cytotoxic effect of calcium-activated neutral proteinase inhibitor

OpenAIRE

Logothetou-Rella, H.

1994-01-01

Phytohaemagglutinin (PHA)-activated lymphocytes differentiated into nuclear vlimata (NVs) in vitro. Lymphocyte attachment was followed by formation and extrusion of cytoplasmic vesicles. nuclear elongation and fragmentation into NVs. NVs and cytoplasmic vesicles were detached and organized into large cell nodules in suspension. Immunocytochemistry showed that T-lymphocytes differentiated mainly to NVs while B-lymphocytes to buds. During differentiation ther...

Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis

NARCIS (Netherlands)

Cantaert, Tineke; Doorenspleet, Marieke E.; Francosalinas, Gabriela; Paramarta, Jaqueline E.; Klarenbeek, Paul L.; Tiersma, Yvonne; van der Loos, Chris M.; de Vries, Niek; Tak, Paul Peter; Baeten, Dominique L.

2012-01-01

Objective Whether and how B lymphocytes contribute to the pathogenesis of spondylarthritis (SpA), a seronegative arthritis associated with gut inflammation, remains unknown. Because innate-like CD5+ B lymphocytes with regulatory functions have been identified in colitis models, we undertook the

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

International Nuclear Information System (INIS)

Barsegian, Vahe; Moeckel, Daniel; Mueller, Stefan P.; Bockisch, Andreas; Horn, Peter A.; Lindemann, Monika

2017-01-01

Therapy with the alpha-emitter radium-223 chloride ("2"2"3Ra) 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 "2"2"3Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving "2"2"3Ra 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 "2"2"3Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

Epstein - Barr virus expression in Hodgkin's disease: Correlation withhistologic subtypes and T and B lymphocyte distribution

International Nuclear Information System (INIS)

Mourad, W.; Bazerbashi, S.; Alsohaibani, Mohamed O.; Saddik, M.

1998-01-01

The pathogenesis of Hodgkin's disease is linked to Epstein-Barr virus(EBV). Some histologic subtypes show a high level of viral expression. Theseinclude mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. GradeII NSHD is a more aggressive variant of HD. Lymphocyte predominant (LPHD) isa B cell lymphoproliferative disorder that has not been associated with EBVexpression. Infiltrating lymphocytes in HD are predominantly T lymphocytes,with minor component of B lymphocytes. In the current study, EBV expressionwas tested in cases of HD in relation to histologic subtypes. An attempt wasmade at correlating EBV expression with T and B lymphocyte distribution inlymph nodes involved by HD. Formalin-fixed paraffin-embedded tissue from 62cases of HD were tested for EBV and mRNA expression, using the EBER-1 probeand in situ hybridization. T and B lymphocyte distribution and their ratioswere evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45RO] andCD20, respectively), and the immunoperoxidase technique. The cases were seenin 38 male and 24 female patients, with an age range of 3 to 72 years (median25 years). There were 30 cases of grade I and 15 cases of grade II NSHD, 9cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases(46%). This expression was seen in 8 cases of grade I NSHD (26%), 13 cases ofgrade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPHDshowed viral expression. T to B lymphocytes ratios in EBV-positive casesranged from 1/6 to 8/1 and ranged from 2/1 to 20/1 in EBV-negative cases(P=0.06). Nine of the 29 positive cases (31%) showed equal T/B lymphocyteratios (n=4), or predominance of B lymphocytes (n=5). None of theEBV-negative cases showed predominance of B lymphocytes. Our study confirmedpreviously reported findings of the prevalence of EBV expression in MCHD andNSHD. Our findings also suggest that EBV expression may be more commonly seenin aggressive forms of HD. Decreased number of T lymphocytes in

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

Energy Technology Data Exchange (ETDEWEB)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

1986-03-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.

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

Science.gov (United States)

Kianmehr, Mojtaba; Hajavi, Jafar; Gazeri, Javad

2017-09-01

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

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

Science.gov (United States)

Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Stimulation of lymphocytes in vitro by Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis sonicates

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Zeijlemaker, W. P.; Meinesz, A. A.; Abraham-Inpijn, L.

1990-01-01

The present study was designed to assess whether the in vitro stimulation of lymphocytes by sonicates of Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis is antigen specific or non-specific. In addition, the role of T and B lymphocytes in these responses was assessed. Peripheral

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

Science.gov (United States)

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

2004-01-01

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

Human thiopurine methyltransferase pharmacogenetics: effect of phenotype on sensitivity of cultured lymphocytes to 6-mercaptopurine

International Nuclear Information System (INIS)

Van Loon, J.; Weinshilboum, R.

1986-01-01

Thiopurine methyltransferase (EC 2.1.1.67, TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP). TPMT activity in human lymphocytes and other tissues is controlled by a common genetic polymorphism. These experiments were designed to study the relationship between TPMT phenotype and the effect of 6-MP on 3 H-thymidine ( 3 H-TdR) incorporation into phytohemaglutinin (PHA) stimulated human peripheral blood lymphocytes. Lymphocytes were obtained from the blood of nine subjects, three subjects with each TPMT phenotype. 6-MP dose response curves were performed at optimal (10 μg/ml) and suboptimal (1 μg/ml) concentrations of PHA. ED50 values for 6-MP with lymphocytes from subjects who genetically lacked TPMT activity were higher than ED50 values for lymphocytes from subjects with genetically intermediate or high TPMT activity. However, ED50 values decreased as level of stimulation increased. Therefore, the effects of 6-MP were studied at a series of PHA concentrations that ranged from 0.1 μg/ml to 10 μg/ml. Lymphocytes from subjects who lacked TPMT activity had significantly higher K/sub ii/ values (1.37 +/- 0.340 μM; mean +/- SEM) for inhibition of 3 H-TdR incorporation by 6-MP than did lymphocytes from subjects with intermediate or high TPMT activity (0.529 +/- 0.068 μM and 0.327 +/- 0.064 μM, respectively, P < .05 for both comparisons)

Human thiopurine methyltransferase pharmacogenetics: effect of phenotype on sensitivity of cultured lymphocytes to 6-mercaptopurine

Energy Technology Data Exchange (ETDEWEB)

Van Loon, J.; Weinshilboum, R.

1986-03-05

Thiopurine methyltransferase (EC 2.1.1.67, TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP). TPMT activity in human lymphocytes and other tissues is controlled by a common genetic polymorphism. These experiments were designed to study the relationship between TPMT phenotype and the effect of 6-MP on /sup 3/H-thymidine (/sup 3/H-TdR) incorporation into phytohemaglutinin (PHA) stimulated human peripheral blood lymphocytes. Lymphocytes were obtained from the blood of nine subjects, three subjects with each TPMT phenotype. 6-MP dose response curves were performed at optimal (10 ..mu..g/ml) and suboptimal (1 ..mu..g/ml) concentrations of PHA. ED50 values for 6-MP with lymphocytes from subjects who genetically lacked TPMT activity were higher than ED50 values for lymphocytes from subjects with genetically intermediate or high TPMT activity. However, ED50 values decreased as level of stimulation increased. Therefore, the effects of 6-MP were studied at a series of PHA concentrations that ranged from 0.1 ..mu..g/ml to 10 ..mu..g/ml. Lymphocytes from subjects who lacked TPMT activity had significantly higher K/sub ii/ values (1.37 +/- 0.340 ..mu..M; mean +/- SEM) for inhibition of /sup 3/H-TdR incorporation by 6-MP than did lymphocytes from subjects with intermediate or high TPMT activity (0.529 +/- 0.068 ..mu..M and 0.327 +/- 0.064 ..mu..M, respectively, P < .05 for both comparisons).

Evaluation of early recognition of viral infections in man. [using specific gravity of lymphocytes

Science.gov (United States)

Kelton, A. A.; Lawton, M. B.

1975-01-01

The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.

Chromosome radiosensitivity and kinetics of proliferation of peripheral lymphocytes in individuals with aneuploid karyotype

Energy Technology Data Exchange (ETDEWEB)

Konecna, H; Kalina, I; Ondrussekova, A

1988-08-01

Experimentally investigated was the radiosensitivity of chromosomes and the kinetics of the proliferation of peripheral lymphocytes in patients with aneuploid (DS and TS) and normal karyotype irradiated in vitro in the G/sub o/ stage of the cell cycle. Trisomic lymphocytes were found to proliferate more rapidly in the in vitro culture and to be more sensitive than diploid cell populations. In monosomic lymphocytes in Turner syndrome patients, the proliferation and incidence of chromosomal abberations was similar to the disomic lines in Down's syndrome patients and in Turner syndrome patients, and to that found in persons with a normal karyotype. The results of the experiment show that there is a relationship between the proliferation rate of peripheral lymphocytes cultures in vitro and the radiosensivity of chromosomes. (author). 1 tab., 3 figs., 11 refs.

Chromosome radiosensitivity and kinetics of proliferation of peripheral lymphocytes in individuals with aneuploid karyotype

International Nuclear Information System (INIS)

Konecna, H.; Kalina, I.; Ondrussekova, A.

1988-01-01

Experimentally investigated was the radiosensitivity of chromosomes and the kinetics of the proliferation of peripheral lymphocytes in patients with aneuploid (DS and TS) and normal karyotype irradiated in vitro in the G o stage of the cell cycle. Trisomic lymphocytes were found to proliferate more rapidly in the in vitro culture and to be more sensitive than diploid cell populations. In monosomic lymphocytes in Turner syndrome patients, the proliferation and incidence of chromosomal abberations was similar to the disomic lines in Down's syndrome patients and in Turner syndrome patients, and to that found in persons with a normal karyotype. The results of the experiment show that there is a relationship between the proliferation rate of peripheral lymphocytes cultures in vitro and the radiosensivity of chromosomes. (author). 1 tab., 3 figs., 11 refs

Genetic modification of lymphocytes by retrovirus-based vectors.

Science.gov (United States)

Suerth, Julia D; Schambach, Axel; Baum, Christopher

2012-10-01

The genetic modification of lymphocytes is an important topic in the emerging field of gene therapy. Many clinical trials targeting immunodeficiency syndromes or cancer have shown therapeutic benefit; further applications address inflammatory and infectious disorders. Retroviral vector development requires a detailed understanding of the interactions with the host. Most researchers have used simple gammaretroviral vectors to modify lymphocytes, either directly or via hematopoietic stem and progenitor cells. Lentiviral, spumaviral (foamyviral) and alpharetroviral vectors were designed to reduce the necessity for cell stimulation and to utilize potentially safer integration properties. Novel surface modifications (pseudotyping) and transgenes, built using synthetic components, expand the retroviral toolbox, altogether promising increased specificity and potency. Product consistency will be an important criterion for routine clinical use. Copyright © 2012. Published by Elsevier Ltd.

Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

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Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

1976-01-01

Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

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

Science.gov (United States)

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

2011-08-15

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

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

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Duran Tok

2014-04-01

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

Staining human lymphocytes and onion root cell nuclei with madder root.

Science.gov (United States)

Cücer, N; Guler, N; Demirtas, H; Imamoğlu, N

2005-01-01

We performed staining experiments on cells using natural dyes and different mordants using techniques that are used for wool and silk dyeing. The natural dye sources were madder root, daisy, corn cockle and yellow weed. Ferrous sulfate, copper sulfate, potassium tartrate, urea, potassium aluminum sulfate and potassium dichromate were used as mordants. Distilled water, distilled water plus ethanol, heptane, and distilled water plus methanol were used as solvents. All dye-mordant-solvent combinations were studied at pH 2.4, 3.2 and 4.2. The generic staining procedure was to boil 5-10 onion roots or stimulated human lymphocyte (SHL) preparations in a dye bath on a hot plate. Cells were examined at every half hour. For multicolor staining, madder-dyed lymphocytes were decolorized, then stained with Giemsa. The AgNOR technique was performed following the decolorization of Giemsa stained lymphocytes. Good results were obtained for both onion root cells and lymphocytes that were boiled for 3 h in a dye bath that included 4 g madder root, 4 g ferrous sulfate as mordant in 50 ml of 1:1 (v/v) methanol:distilled water. The pH was adjusted to 4.2 with 6 ml acetic acid. We conclude that madder root has potential as an alternative dye for staining biological materials.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-01

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

Immunomodulatory effects of Bacteroides products on in vitro human lymphocyte functions.

Science.gov (United States)

Shenker, B J; Slots, J

1989-03-01

Bacteroides spp. have been implicated in the pathogenesis of several diseases, including periodontal diseases. In this study sonic extracts of 6 Bacteroides spp. were examined for their abilities to alter human lymphocyte function. We found that soluble extracts from Bacteroides intermedius, Bacteroides endodontalis, Bacteroides asaccharolyticus, Bacteroides melaninogenicus, and to a lesser degree Bacteroides loescheii, caused dose-dependent inhibition of human lymphocyte responsiveness to both mitogens and antigens. Suppression involved altered DNA, RNA and protein synthesis as well as immunoglobulin production. In contrast, Bacteroides gingivalis did not suppress these responses; instead, it stimulated lymphocyte proliferation and enhanced immunoglobulin production. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbial mediated immunosuppression may conceivably alter the nature and consequences of host-parasite interactions in periodontal disease.

Changes in the host lymphocyte subsets during chemical carcinogenesis

International Nuclear Information System (INIS)

Brodt, P.; Lala, P.K.

1983-01-01

Changes in small lymphocyte subsets in the lymphoid organs of young C3H mice were studied following i.m. injection of a carcinogenic dose of 3-methylcholanthrene (mc). Using monoclonal anti-Lyt antibodies and a sandwich radiolabeling method with 125 I-labeled rabbit anti-mouse Immunoglobulin, the lymphocyte subpopulations in the thymus, spleen, and draining lymph node were examined by radioautography. During the fifth week following the administration of the carcinogen a sharp decrease in the level of Ly-1,2+ small lymphocyte population in the thymus was noted which coincided with a considerable increase (10-fold) in the Ly-2+. During the same period, a similar increase in the Ly-2+ population was also observed in the draining. The high levels of Ly-2+ cells lasted for more than 4 weeks in the thymus while, in the draining node, they lasted for 2 weeks and dropped to normal levels (0 to 2%) simultaneously with the appearance of tumor cells identified in histological preparations. These systemic increases coincided with the appearance of macroscopic tumor nodules. The mixed lymphocyte reaction response of the draining node cells, but not of the spleen, was suppressed during the period of increased level of Ly-2+ cells. Furthermore, during this period, s.c. transplantation of a syngeneic mammary tumor in the same leg resulted in enhanced local growth as well as metastatic spread of the tumor to the lungs in mc treated mice. These findings suggest that a localized immunosuppression associated with the rise in the Ly-2+ cells may be of functional significance during carcinogen-induced tumor development

Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

1981-01-01

Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

Effects of noise exposure on catalase activity of growing lymphocytes

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Syed Kashif Nawaz

2012-11-01

Full Text Available Oxidative stress due to noise was estimated at cell level using model of growing lymphocytes. Lymphocytes were isolated and cultured using conventional methodology. Cell culture of each group was exposed to sound of frequency 1 KHz during incubation. Three groups were defined on the basis of exposure of sound with specific range of intensity and duration of exposure. Group A and Group B were exposed to sound with intensity 110 dBA for four hours per day and for eight hours per day respectively. Control group was exposed to sound less than 85 dBA. Viable cell count was performed using trypan blue. Catalase activity of each group was estimated using ELISA kit.Viable cell count of Group A and Group B was almost same but significantly less than that of control group. Catalase activity of lymphocytes in Group B was significantly low as compared to Group A and controls (p=0.003,p< 0.05. There was no significant difference between catalase activity of Group A and control group.Exposure of sound with frequency 1 KHz and intensity 110 dBA for 4 hours and eight hours per day may induce oxidative stress in growing lymphocytes causing the difference in viable cell count. However the catalase activity depends on duration of exposure. In case of noise exposure of 8 hours per day, it declines significantly as compared to noise exposure of 4 hours per day.

Protective effect of citrullus vulgaris on irradiated lymphocyte membrane ultrastructure

International Nuclear Information System (INIS)

Khairul Osman; Norashikin, M.S.; Hing Hiang Lian; Siti Fatimah Ibrahim; Seetha Khartini Abdul Wahab; Jamaludin Mohamed; Proom Promwichit

2004-01-01

Radiotherapy causes various complications including low immunity. Past research that the low immunity is due to the low amount of lymphocytes and consumption vulgaris will alleviate this problem. Based on this a study was conducted to identify vulgaris was able to produce radioprotection on the lymphocyte membrane. A total of 30 adult male Sprague-Dawley rats were used and divided into three equals groups of positive control and treatment. For seven days, positive control and negative control were force fed with normal saline of 40 ml/kg animal weight while the treatment group received 40g/kg animal weight fresh juice of citrullus vulgaris daily. After a week positive control an group were irradiated with 0.9 Gy gamma ray. Viable lymphocyte were determined using propidium iodine and acridine orange stain. Results clearly shows that positive con and treatment group were significantly different at 34 ± 3% , 80 ± 2% an 71 ± 2% respectively. SEM results shows that pores were present on the membrane of the pos while the negative control had none. Similar results were also found on the treatment group. Based on the result it had shown that citrullus vulgaris had radioprotection properties and lymphocytes were destroyed by the formation of pores on their membrane. It is very likely that the radioprotection properties could be due to the presence of antioxidants particularly vitamin A, C and lycopene. In conclusion, citrullus vulgaris could be used as a safe radioprotection agent. (Author)

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

Science.gov (United States)

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

2014-01-01

During the last decades, a multitude of studies applying distinct in vitro and in vivo model systems have contributed greatly to our better understanding of the initiation and regulation of inflammatory processes leading to allergic diseases. Over the years, it has become evident that among lymphocytes, not only IgE-producing B cells and allergy-orchestrating CD4(+) helper cells but also cytotoxic CD8(+) T cells, γδ-T cells and innate lymphoid cells, as well as regulatory lymphocytes, might critically shape the immune response towards usually innocuous allergens. In this review, we provide a historic overview of pioneering work leading to the establishment of important lymphocyte-based model systems for allergy research. Moreover, we contrast the original findings with our currently more refined knowledge to appreciate the actual validity of the respective models and to reassess the conclusions obtained from them. Conflicting studies and interpretations are identified and discussed. The tables are intended to provide an easy overview of the field not only for scientists newly entering the field but also for the broader readership interested in updating their knowledge. Along those lines, herein we discuss in vitro and in vivo approaches to the investigation of lymphocyte effector cell activation, polarization and regulation, and describe depletion and adoptive transfer models along with gene knockout and transgenic (tg) methodologies. In addition, novel attempts to establish humanized T cell antigen receptor tg mouse models for allergy research are described and discussed. © 2014 S. Karger AG, Basel.

Lymphocyte interactions with the extracellular matrix of malignant cells in vítro: A morphological and immunocytochemical study

OpenAIRE

Logothetou-Rella, H.

1993-01-01

The interactions of lymphocytes with the glycosaminoglycans-protease-membrane extracellular matrix, produced by mixed cell cultures of normal with malignant cell clones, were examined. Pre-activated and activated heterologous peripheral lymphocytes were used. Co-cultures of activated lymphocytes with al1 cell types used, formed identical cell nodules. Histology of cell nodules showed that activated lymphocytes were cytolytic to pure normal or malignant cell clo...

Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

2012-08-01

Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

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

The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full...... 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...

The influence of aminophylline on the nanostructure and nanomechanics of T lymphocytes: an AFM study

Science.gov (United States)

Huang, Xun; He, Jiexiang; Liu, Mingxian; Zhou, Changren

2014-09-01

Although much progress has been made in the illustration of the mechanism of aminophylline (AM) treating asthma, there is no data about its effect on the nanostructure and nanomechanics of T lymphocytes. Here, we presented atomic force spectroscopy (AFM)-based investigations at the nanoscale level to address the above fundamental biophysical questions. As increasing AM treatment time, T lymphocytes' volume nearly double increased and then decreased. The changes of nanostructural features of the cell membrane, i.e., mean height of particles, root-mean-square roughness (Rq), crack and fragment appearance, increased with AM treatment time. T lymphocytes were completely destroyed with 96-h treatment, and they existed in the form of small fragments. Analysis of force-distance curves showed that the adhesion force of cell surface decreased significantly with the increase of AM treatment time, while the cell stiffness increased firstly and then decreased. These changes were closely correlated to the characteristics and process of cell oncosis. In total, these quantitative and qualitative changes of T lymphocytes' structure and nanomechanical properties suggested that AM could induce T lymphocyte oncosis to exert anti-inflammatory effects for treating asthma. These findings provide new insights into the T lymphocyte oncosis and the anti-inflammatory mechanism and immune regulation actions of AM.

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

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Pavlica Ljiljana

2003-01-01

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

Predictive contribution of neutrophil/lymphocyte ratio in diagnosis of brucellosis.

Science.gov (United States)

Olt, Serdar; Ergenç, Hasan; Açıkgöz, Seyyid Bilal

2015-01-01

Here we wanted to investigate predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis of brucellosis. Thirty-two brucellosis patients diagnosed with positive serum agglutination test and thirty-two randomized healthy subjects were enrolled in this study retrospectively. Result with ROC analyzes the baseline NLR and hemoglobin values were found to be significantly associated with brucellosis (P = 0.01, P = 0.01, resp.). Herein we demonstrated for the first time that NLR values were significantly associated with brucellosis. This situation can help clinicians during diagnosis of brucellosis.

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

International Nuclear Information System (INIS)

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

1977-01-01

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

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

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P.A. Nascimento

2001-02-01

Full Text Available Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

The role of lymphocytes in radiotherapy-induced adverse late effects in the lung

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Florian Wirsdörfer

2016-12-01

Full Text Available Radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation. Thoracic irradiation triggers acute and chronic environmental lung changes that are shaped by the damage response of resident cells, by the resulting reaction of the immune system, and by repair processes. Although considerable progress has been made during the last decade in defining involved effector cells and soluble mediators, the network of pathophysiological events and the cellular cross-talk linking acute tissue damage to chronic inflammation and fibrosis still require further definition. Infiltration of cells from the innate and adaptive immune systems is a common response of normal tissues to ionizing radiation. Herein lymphocytes represent a versatile and wide-ranged group of cells of the adaptive immune system that can react under specific conditions in various ways and participate in modulating the lung environment by adopting pro-inflammatory, anti-inflammatory or even pro- or anti-fibrotic phenotypes. The present review provides an overview on published data about the role of lymphocytes in radiation-induced lung disease and related damage-associated pulmonary diseases with a focus on T-lymphocytes and B-lymphocytes. We also discuss the suspected dual role of specific lymphocyte subsets during the pneumonitic phase and fibrotic phase that is shaped by the environmental conditions and the interaction and the intercellular cross-talk between cells from the innate and adaptive immune systems and (damaged resident epithelial cells and stromal cells (e.g. endothelial cells, mesenchymal stem cells (MSC, fibroblasts. Finally, we highlight potential therapeutic targets suited to counteract pathological lymphocyte responses to prevent or treat radiation-induced lung disease.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

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Chen, Liming; Liu, Yinghui; Dong, Liangliang; Chu, Xiaoxia

2015-03-01

Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p edaravone offers protection from radiation-induced cytogenetic alterations.

Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

African Journals Online (AJOL)

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

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

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MARISOL HERRERA-RIVERO

2013-01-01

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

Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on human blood lymphocytes.

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Salimi, Ahmad; Alami, Bahare; Pourahmad, Jalal

2017-08-01

The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical and flow cytometry assessments, we demonstrated that addition of CHG at 1 μM concentration to human blood lymphocytes induced cytotoxicity following 6 h. The CHG-induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species generation, mitochondrial membrane potential collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, CHG triggers oxidative stress and organelles damages in lymphocytes which are important cells in defense against foreign agents. Finally our findings suggest that using of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with CHG. © 2017 Wiley Periodicals, Inc.

Effect of low dose tritium on mouse lymphocyte DNA estimated by comet assay

International Nuclear Information System (INIS)

Ichimasa, Yusuke; Otsuka, Kensuke; Maruyama, Satoko; Tauchi, Hiroshi; Ichimasa, Michiko; Uda, Tatsuhiko

2003-01-01

This paper deals with low dose effect of HTO on mouse lymphocytes DNA (in vitro irradiation) estimated by the comet assay using ICR male mouse of 20 to 23 weeks old. Lymphocytes were isolated by centrifugation of whole blood sample on Ficoll-Paque solution and embedded in agarose gel just after mixed with HTO. After lymphocytes were exposed to 17-50 mGy of HTO, the agarose gel slides were washed to remove HTO and cell lysis treatment on the slides was conducted before electrophoresis. The individual comets on stained slides after electrophoresis were analyzed using imaging software. No significant DNA damages were observed. (author)

Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.

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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.

Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

NARCIS (Netherlands)

Malviya, Gaurav; D'Alessandria, Calogero; Bonanno, Elena; Vexler, Vladimir; Massari, Roberto; Trotta, Carlo; Scopinaro, Francesco; Dierckx, Rudi; Signore, Alberto

2009-01-01

Visilizumab is an IgG(2) humanized monoclonal antibody (mAb) characterized by non-Fc gamma R binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a

Measurement of in vivo HGPRT-deficient mutant cell frequency using a modified method for cloning human peripheral blood T-lymphocytes

International Nuclear Information System (INIS)

Hakoda, Masayuki; Akiyama, Mitoshi; Kyoizumi, Seishi; Kobuke, Kyoko; Awa, A.A.

1987-07-01

Approximately 80 % of human peripheral blood T-lymphocytes could be cloned in the presence of crude Interleukin-2, phytohemagglutinin, and X-irradiated autologous lymphocytes and Raji B-cells. This modified cloning method was used to measure the in vivo frequency of HGPRT-deficient mutant T-lymphocytes. Repeated experiments using blood from the same individuals revealed that the frequency of mutant cells was almost constant for each individual even though the cloning efficiency of lymphocytes varied somewhat from experiment to experiment. Approximately 80 % of both wild-type unselected and 6-thioguanine-resistant colonies had helper/inducer and about 20 % had suppressor/cytotoxic T-lymphocyte markers. No difference was observed in the distribution of lymphocyte subsets between wild and mutant lymphocyte colonies. (author)

Neutrophil to lymphocyte with monocyte to lymphocyte ratio and white blood cell count in prediction of lung cancer

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Thang Thanh Phan

2018-04-01

Full Text Available Background Lung cancer is the most common cause of cancer deaths in both sexes, while it is very difficult for screenings and early detection. Aims This study aims to clarify the role of systematic inflammation markers, including white blood cell (WBC, neutrophil (NEU, monocyte (MONO, platelet (PLT, neutrophil to lymphocyte ratio (NLR, monocyte to lymphocyte ratio (MLR and platelet to lymphocyte ratio (PLR in prediction of lung cancer. Methods A case-control study was conducted on 1,315 primary lung cancer patients and 1,315 healthy adults with matched age and gender at Cho Ray hospital. NLR, MLR and PLR were calculated by using neutrophil, lymphocyte, monocyte and platelet count which were recalled from laboratory database. With 600 cases in the derivation set, the logistic regression with univariate analysis was used to identify the impacted marker, then developing the optimal prediction model for lung cancer by logistic regression with multivariate method. The diagnostic values of optimal model consisting of sensitivity (Sen, specificity (Spe, positive predictive value (PPV, negative predictive value (NPV and the area under the ROC curve (AUC value were extracted and verified on all data, in validation set. Results The median values of WBC, NEU, MONO, PLT, NLR, MLR and PLR in lung cancer were not significantly difference between histological subtypes and clinical stages (p > 0.05, but higher than the values in control group (p < 0.01. Multivariates analysis shows that NLR, MLR and WBC were three parameters that have the significant impact of the optimal prediction model (p < 0.01. The AUC value, sensitivity and specificity of the optimal model for lung cancer detection were 0.881, 73.5 per cent (95 per cent CI:70.3–76.6 and 87.7 per cent (95 per centCI:85.2–89.9, respectively. Whereas, the PPV and NPV values of prediction model were 85.7 per cent (95 per cent CI:82.8–88.2 and 76.8 (95 per centCI:73.9–79.5, respectively. Among three

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

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V. N. Mineev

2010-01-01

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

Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice.

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Liu, Yin; Belkina, Natalya V; Park, Chung; Nambiar, Raj; Loughhead, Scott M; Patino-Lopez, Genaro; Ben-Aissa, Khadija; Hao, Jian-Jiang; Kruhlak, Michael J; Qi, Hai; von Andrian, Ulrich H; Kehrl, John H; Tyska, Matthew J; Shaw, Stephen

2012-01-12

ERM (ezrin, radixin moesin) proteins in lymphocytes link cortical actin to plasma membrane, which is regulated in part by ERM protein phosphorylation. To assess whether phosphorylation of ERM proteins regulates lymphocyte migration and membrane tension, we generated transgenic mice whose T-lymphocytes express low levels of ezrin phosphomimetic protein (T567E). In these mice, T-cell number in lymph nodes was reduced by 27%. Lymphocyte migration rate in vitro and in vivo in lymph nodes decreased by 18% to 47%. Lymphocyte membrane tension increased by 71%. Investigations of other possible underlying mechanisms revealed impaired chemokine-induced shape change/lamellipod extension and increased integrin-mediated adhesion. Notably, lymphocyte homing to lymph nodes was decreased by 30%. Unlike most described homing defects, there was not impaired rolling or sticking to lymph node vascular endothelium but rather decreased migration across that endothelium. Moreover, decreased numbers of transgenic T cells in efferent lymph suggested defective egress. These studies confirm the critical role of ERM dephosphorylation in regulating lymphocyte migration and transmigration. Of particular note, they identify phospho-ERM as the first described regulator of lymphocyte membrane tension, whose increase probably contributes to the multiple defects observed in the ezrin T567E transgenic mice.

Serine esterase and hemolytic activity in human cloned cytotoxic T lymphocytes

OpenAIRE

1988-01-01

Target cell lysis by most murine cytotoxic T lymphocytes appears to be mediated by a complement (C9)-like protein called perforin, contained in high-density cytoplasmic granules. These granules also contain high levels of serine esterase activity, which may also play a role in cytolysis. Analysis of 17 cloned human cytotoxic T lymphocytes revealed the presence of serine esterase that is very similar to its murine counterpart in substrate and inhibitor specificities, pH optimum, and molecular ...

Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions.

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Nakasaki, Tae; Tanaka, Toshiyuki; Okudaira, Shinichi; Hirosawa, Michi; Umemoto, Eiji; Otani, Kazuhiro; Jin, Soojung; Bai, Zhongbin; Hayasaka, Haruko; Fukui, Yoshinori; Aozasa, Katsuyuki; Fujita, Naoya; Tsuruo, Takashi; Ozono, Keiichi; Aoki, Junken; Miyasaka, Masayuki

2008-11-01

Autotaxin (ATX) is a secreted protein with lysophospholipase D activity that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine. Here we report that functional ATX is selectively expressed in high endothelial venules (HEVs) of both lymph nodes and Peyer's patches. ATX expression was developmentally regulated and coincided with lymphocyte recruitment to the lymph nodes. In adults, ATX expression was independent of HEV-expressed chemokines such as CCL21 and CXCL13, innate immunity signals including those via TLR4 or MyD88, and of the extent of lymphocyte trafficking across the HEVs. ATX expression was induced in venules at sites of chronic inflammation. Receptors for the ATX enzyme product LPA were constitutively expressed in HEV endothelial cells (ECs). In vitro, LPA induced strong morphological changes in HEV ECs. Forced ATX expression caused cultured ECs to respond to lysophosphatidylcholine, up-regulating lymphocyte binding to the ECs in a LPA receptor-dependent manner under both static and flow conditions. Although in vivo depletion of circulating ATX did not affect lymphocyte trafficking into the lymph nodes, we surmise, based on the above data, that ATX expressed by HEVs acts on HEVs in situ to facilitate lymphocyte binding to ECs and that ATX in the general circulation does not play a major role in this process. Tissue-specific inactivation of ATX will verify this hypothesis in future studies of its mechanism of action.

In Utero Exposure to Histological Chorioamnionitis Primes the Exometabolomic Profiles of Preterm CD4+ T Lymphocytes.

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Matta, Poojitha; Sherrod, Stacy D; Marasco, Christina C; Moore, Daniel J; McLean, John A; Weitkamp, Joern-Hendrik

2017-11-01

Histological chorioamnionitis (HCA) is an intrauterine inflammatory condition that increases the risk for preterm birth, death, and disability because of persistent systemic and localized inflammation. The immunological mechanisms sustaining this response in the preterm newborn remain unclear. We sought to determine the consequences of HCA exposure on the fetal CD4 + T lymphocyte exometabolome. We cultured naive CD4 + T lymphocytes from HCA-positive and -negative preterm infants matched for gestational age, sex, race, prenatal steroid exposure, and delivery mode. We collected conditioned media samples before and after a 6-h in vitro activation of naive CD4 + T lymphocytes with soluble staphylococcal enterotoxin B and anti-CD28. We analyzed samples by ultraperformance liquid chromatography ion mobility-mass spectrometry. We determined the impact of HCA on the CD4 + T lymphocyte exometabolome and identified potential biomarker metabolites by multivariate statistical analyses. We discovered that: 1) CD4 + T lymphocytes exposed to HCA exhibit divergent exometabolomic profiles in both naive and activated states; 2) ∼30% of detected metabolites differentially expressed in response to activation were unique to HCA-positive CD4 + T lymphocytes; 3) metabolic pathways associated with glutathione detoxification and tryptophan degradation were altered in HCA-positive CD4 + T lymphocytes; and 4) flow cytometry and cytokine analyses suggested a bias toward a T H 1-biased immune response in HCA-positive samples. HCA exposure primes the neonatal adaptive immune processes by inducing changes to the exometabolomic profile of fetal CD4 + T lymphocytes. These exometabolomic changes may link HCA exposure to T H 1 polarization of the neonatal adaptive immune response. Copyright © 2017 by The American Association of Immunologists, Inc.

Absorption and fluorescence studies of curcumin bound to liposomes and lymphocytes: effect of γ- irradiation

International Nuclear Information System (INIS)

Kunwar, Amit; Barik, A.; Indira Priyadarsini, K.; Pandey, R.

2006-01-01

Absorption and fluorescence spectral changes in curcumin were employed to follow its binding to liposomes and lymphocytes. The association constants indicated high affinity of curcumin to liposomes. Tumor lymphocytes show mere intense fluorescence of curcumin over the normal lymphocytes. The loss of curcumin in cells after γ-irradiation could be followed by reduction in curcumin fluorescence. The studies indicate that such fluorescence changes can be used as markers to understand the preferential loading of curcumin to cells. (author)

Absorption and fluorescence studies of curcumin bound to liposomes and lymphocytes: effect of {gamma}- irradiation

Energy Technology Data Exchange (ETDEWEB)

Kunwar, Amit; Barik, A; Indira Priyadarsini, K [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Pandey, R [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai (India)

2006-01-15

Absorption and fluorescence spectral changes in curcumin were employed to follow its binding to liposomes and lymphocytes. The association constants indicated high affinity of curcumin to liposomes. Tumor lymphocytes show mere intense fluorescence of curcumin over the normal lymphocytes. The loss of curcumin in cells after {gamma}-irradiation could be followed by reduction in curcumin fluorescence. The studies indicate that such fluorescence changes can be used as markers to understand the preferential loading of curcumin to cells. (author)

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...

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Carotenoids located in human lymphocyte subpopulations and Natural Killer cells by Raman microspectroscopy

NARCIS (Netherlands)

Puppels, G.J.; Puppels, G.J.; Garritsen, H.S.P.; Garritsen, H.S.P.; Kummer, J.A.; Greve, Jan

1993-01-01

The presence and subcellular location of carotenoids in human lymphocyte sub-populations (CD4+, CD8+, T-cell receptor-γδ+, and CD19+ ) and natural killer cells (CD16+ ) were studied by means of Raman microspectroscopy. In CD4+ lymphocytes a high concentration (10-3M) of carotenoids was found in the

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

NARCIS (Netherlands)

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

1995-01-01

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

Lymphocyte electrotaxis in vitro and in vivo.

Science.gov (United States)

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

2008-08-15

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

Biological Prognostic Markers in Chronic Lymphocytic Leukemia

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Vladimíra Vroblová

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Addition of exogenous cytokines in mixed lymphocyte culture for selecting related donors for bone marrow transplantation

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Jeane Eliete Laguila Visentainer

Full Text Available CONTEXT: Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests. OBJECTIVE: To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection. TYPE OF STUDY: Prospective study. SETTING: Bone Marrow Transplantation Unit, Universidade Estadual de Campinas. PARTICIPANTS: Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures. PROCEDURES: Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA. MAIN MEASUREMENTS: Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2. RESULTS: In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001 and 6.4 using IL-2 (p < 0.001, for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001 and 4.1 using IL-2 (p < 0.001. For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001. Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses. CONCLUSION: IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less

Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation

International Nuclear Information System (INIS)

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

1999-01-01

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

Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation

Energy Technology Data Exchange (ETDEWEB)

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

1999-04-01

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

Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

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Lavin, M.F.; Jennings, P.A.; Hughes, D.J. (Queensland Univ., Brisbane (Australia))

1982-05-01

Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds.

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

International Nuclear Information System (INIS)

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

2003-01-01

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

Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters

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Anila, KR; Nayak, Nileena; Jayasree, K

2016-01-01

Introduction: Chronic lymphocytic thyroiditis [Hashimoto thyroiditis (HT)] is a common thyroid lesion diagnosed on fine-needle aspiration cytology (FNAC). Apart from FNAC, various other parameters, such as clinical features, ultrasonographic findings, antithyroid antibody levels, hormone profiles, and radionuclide thyroid scan, are also taken into consideration in making a diagnosis of HT. Aims: To grade lymphocytic thyroiditis based on the cytomorphology and to correlate the cytological grades with the levels of antithyroid peroxidase antibody (ATPO), antithyroglobulin antibody (ATG), and thyroid stimulating hormone (TSH). Materials and Methods: During a period of one and half years, 1,667 cases underwent FNAC of thyroid at our tertiary care center. Of these, 128 cases had cytological evidence of lymphocytic thyroiditis. Out of these, in 60 cases the levels of ATPO, ATG, and TSH were known. The cytological grades of lymphocytic thyroiditis in these cases were correlated with these parameters. Results: Out of the 60 cases, 55 were females. Age ranged from 5 years to 70 years, with majority of patients in third decade. Diffuse enlargement of thyroid was the commonest presentation. However, 14 cases presented with nodular disease. Majority of the patients had grade 1 thyroiditis (27 cases), followed by grade 2 thyroiditis (22 cases). Cytomorphology was diagnostic of thyroiditis in all 60 cases. ATPO was elevated in 57 cases and ATG was elevated in 40 cases. Elevated level of TSH was seen in only 18 cases. In 39 cases, TSH value was normal. There was no correlation between the cytological grades of thyroiditis and the levels of antithyroid antibodies and TSH. Conclusion: Lymphocytic infiltration of thyroid follicles is pathognomonic of lymphocytic thyroiditis. Positivity for antithyroid antibodies is strongly associated with HT but no correlation was observed between the grades of thyroiditis and the levels of ATPO, ATG, and TSH. PMID:27756987

Investigation of micronuclei induction in human peripheral blood lymphocytes exposed in vitro to EMF RF

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Kolomiets, Irina A.; Triapitsina, Galina A.; Polevik, Nikolai D.; Pryakhin, Evgeny A.

2008-01-01

Full text: The widespread application of cellular phones is of great concern in view possible consequences for human health. The aim of this study is to assess the capability of electromagnetic fields (EMF) RF with frequency 925 MHz and modulation 217 Hz to induce genotoxic effects as evaluated by the in vitro micronucleus assay on peripheral blood lymphocytes. The flasks of peripheral blood samples collected from healthy volunteers (5 men and 5 women) were placed just on the oscillator of emitting antenna. The signals were produced by the laboratory research plant and were evaluated at four specific absorption rates (SARs) - 0; 0.29; 1.2; 8.1 W/kg. SARs were determined by the calorimetric method. Phytohaemagglutinin stimulated lymphocytes were exposed three times for 10 minutes in the G o (the first 30 minutes after the beginning of cultivation), S (24 hours later), G 2 -M (after 48 hours from the beginning of cultivation) stages of the cell cycle. 72-hours cultures of lymphocytes were examined to determine the extent of micronuclei. The Mann-Whitney U-test was used to evaluate the significance for comparison. The data indicated a significant increase of micronuclei in human lymphocytes exposed to EMF RF (6.5 ± 0.51 0/00; 7.1 ± 0.66 0/00; 7.0 ± 0.50 0/00) in comparison with sham-exposed lymphocytes (3.0 ± 0.60 0/00). There was not revealed a dose-dependent increase of micronuclei in human lymphocytes. It was suggested that the increase of micronuclei in lymphocytes is explicated by a particularity of EMF RF just near the oscillator of emitting antenna. (author)

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

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A.J.L. Torres

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

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

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Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

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Lewintre, Eloisa Jantus; Martín, Cristina Reinoso; Ballesteros, Carlos García; Montaner, David; Rivera, Rosa Farrás; Mayans, José Ramón; García-Conde, Javier

2009-02-01

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

A specific immune tolerance toward offspring cells is to exist after the mother lymphocyte infusion.

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Xing, Haizhou; Liu, Shiqin; Chen, Xue; Fang, Fang; Wu, Xueqiang; Zhu, Ping

2017-04-01

To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10 7 of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed. Maternal lymphocytes were more likely to survive in offspring. At 120h after infusion, the percentages of maternal cells in the offspring were 0.52±0.11% in lymph nodes, 0.97±0.04% in peripheral blood, and 0.97±0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus. Specific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects. Copyright © 2017 Elsevier GmbH. All rights

Acute lymphocytic crisis following herpes simplex type 1 virus hepatitis in a nonimmunocompromised man: a case report

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Plastiras Sotiris

2009-08-01

Full Text Available Abstract Introduction An increase in circulating lymphocytes can be seen following infections such as infectious mononucleosis and pertussis, or in lymphoproliferative disorders such as acute and chronic lymphocytic leukemia. Acute lymphocytic crisis following herpes simplex virus hepatitis has not been described in the literature. Case presentation A 52-year-old man was admitted to our hospital reporting low-grade fever for the previous seven days, and fatigue. During the fifth day of hospitalization, the patient developed a lymphocytic crisis and, after further tests the patient was diagnosed as having herpes simplex virus hepatitis. Conclusion This case report shows that herpes simplex virus type 1 is a possible cause of an acute lymphocytic crisis similar to other well known infectious agents such as Epstein–Barr virus, cytomegalovirus, human immunodeficiency virus, human herpes virus type 6, adenovirus, toxoplasma and human T-cell lymphotropic virus. Furthermore, this case report expands the clinical spectrum of herpes simplex virus hepatitis, since it is reported in a nonimmunocompromised patient presenting with atypical acute lymphocytic syndrome.

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

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

2009-01-01

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

Genotoxic effect of radio marked lymphocytes using Tc-99m complexes

International Nuclear Information System (INIS)

Pedraza L, M.; Ferro F, G.; Mendiola C, M.T.; Morales R, P.

1997-01-01

The genotoxic effect of radio marked lymphocytes was evaluated using 99m -Tc-HMPAO and 99m -Tc- gentisic acid complexes. With the results of this work it is pretended to contribute to the knowledge of genetic and structural damages that provokes the radiation in the marked lymphocytes. The d, 1-HMPAO was synthesized in laboratory with a yielding of 30 %. The radiochemical purity of the complexes was greater than 85%. Mouse lymphocytes obtained of sanguineous volumes 2 ml were used. The radio marked efficiency of cells was 19.6 ± 6.4% and 25.6 ± 5.8% for 99m Tc-HMPAO and 99m Tc gentisic acid respectively. The genotoxic effect was evaluated using the technique of Unicellular Electrophoresis in Micro gel (Comet assay). The results showed that both 99m Tc complexes produce genotoxicity due to their capacity to penetrate cells, therefore the Auger and M internal conversion electrons place all their energy obtaining doses of Gray order. (Author)

Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

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Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

2015-09-01

Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

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

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T. V. Tyrinova

2012-01-01

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

Range-reference determination of lymphocyte subsets in Moroccan

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Centre de Transfusion Sanguine, Hôpital Militaire d'Instruction Med V Rabat, Morocco. 3. Service ... The percentage of CD3-CD56+ subsets was affected by smoking (p < 0.01). Our analysis .... lymphocyte subpopulations in non-smokers and.

The effect of 3-aminobenzamide on X-ray induction of chromosome aberrations in Down syndrome lymphocytes

International Nuclear Information System (INIS)

McLaren, R.A.; Au, W.W.; Legator, M.S.

1989-01-01

Human lymphocytes from normal and Down syndrome (DS) subjects were examined to determine the effect of 3-aminobenzamide (3AB) on X-ray-induced chromosome aberrations. Lymphocytes were treated with 150 or 300 rad of X-rays in the presence of 3 mM 3AB for various times after irradiation, and then the cells were analyzed for the presence of chromosome aberrations in mitotic cells. 3-Aminobenzamide had no effect on the frequency of chromosome aberrations as a result of treatment with X-rays in the presence of 3AB. These observations indicate that DS lymphocytes are more sensitive to the inhibition of poly(ADP)ribose synthetase than normal lymphocytes. (author). 44 refs.; 3 tabs

Chronic lymphocytic leukaemia manifestating as exfoliative dermatitis

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Dhir R

1995-01-01

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

Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

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Ghiotto, Fabio; Fais, Franco; Valetto, Angelo; Albesiano, Emilia; Hashimoto, Shiori; Dono, Mariella; Ikematsu, Hideyuki; Allen, Steven L.; Kolitz, Jonathan; Rai, Kanti R.; Nardini, Marco; Tramontano, Anna; Ferrarini, Manlio; Chiorazzi, Nicholas

2004-01-01

Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged VHDJH and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb’s reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG+ B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both. PMID:15057307

Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

International Nuclear Information System (INIS)

Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

1987-01-01

Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects

The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

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María Guadalupe Reyes García

2013-01-01

Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase

International Nuclear Information System (INIS)

Knox, S.; Misra, H.P.; Shifrine, M.

1982-01-01

Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 μg catalase or 100 μg SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p 2 - and/or H 2 O 2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis. (author)

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-28

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

Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

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Ibrahim Mansur

2016-01-01

Full Text Available Radiotherapy is commonly used to kill malignant cells, but it can significantly deplete hematopoietic and splenic erythroblasts. Radioprotective agents are therefore very important in clinical radiotherapy. We examined the effect of poly-herbal EMSA ERITIN on immunological responses when administered to sublethally irradiated mice with the aim of highlighting promotes erythroid lineages and lymphocytes migration in irradiated mice with the parameter are TER119+CD123+in bone marrow and SDF-1 in bone marrow and spleen organ. Normal BALB/c mice were sublethally irradiated with 600 rad. EMSA ERITIN was administered orally at different doses:(1.04, 3.125 and 9.375 mg/g body weight for 15 days. On day 16 erythroid lineages (TER-119+CD123+ were observed in bone marrow and lymphocytes migration by the production of SDF-1 in spleen and bone marrow. Lymphocytes migration was indicated by the production of SDF-1 in spleen and bone marrow using flow cytometry analysis. EMSA ERITIN increased the generation of erythroid lineage cells marked by TER119+CD123+ and promoted lymphocyte migration by increasing SDF-1 production in bone marrow and spleen. EMSA ERITIN appears to be a powerful medicinal herb with potential as a food supplement to normalize homeostasis and erythropoiesis after radiation.

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

Science.gov (United States)

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

2017-05-01

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

Flow cytometric analysis of lymphocytes in aplastic anemia among atomic bomb survivors

International Nuclear Information System (INIS)

Imamura, Nobutaka; Inada, Tominari; Asaoku, Hideki; Abe, Kazuhiro; Oguma, Nobuo; Kuramoto, Atsushi

1986-01-01

In 6 patients with aplastic anemia and 3 patients with pernicious anemia, lymphocyte subpopulations in the peripheral blood were measured, before and after steroid therapy, with a fluorescence-activated cell sorder using various monoclonal antibodies. The ratio of OKT4-positive lymphocytes (T4) to OKT8-positive lymphocytes (T8) in the peripheral blood was reduced in 2 patients (20 %). The T4/T8 ratio returned to normal during remission of anemia. Hematological improvement was seen after a large amount of steroid therapy in 3 patients. The number of Tac-positive cells tended to decrease and the T4/T8 ratio tended to return to normal with hematological improvement, although there was no correlation to hydrocortisone reaction. Some patients were supposed to have abnormal number of suppressor and inducer T cells. (Namekawa, K.)

Phosphatidylinositol response and proliferation of oxidative enzyme-activated human T lymphocytes: suppression by plasma lipoproteins

International Nuclear Information System (INIS)

Akeson, A.L.; Scupham, D.W.; Harmony, J.A.

1984-01-01

The phosphatidylinositol (PI) response and DNA synthesis of neuraminidase and galactose oxidase (NAGO)-stimulated human T lymphocytes are suppressed by low density lipoproteins (LDL). To understand the mechanism of lymphocyte activation more fully, the PI response and DNA synthesis and suppression of these events by LDL in NAGO-stimulated T lymphocytes were characterized. Between 30 min and 6 hr after NAGO stimulation, there was an increase of 32 Pi incorporation into PI without increased incorporation into the phosphorylated forms of PI or into other phospholipids. DNA synthesis as determined by [ 3 H]thymidine incorporation depended on the lymphocyte-accessory monocyte ratio and total cell density. Optimal stimulation of the PI response and DNA synthesis occurred at the same concentration of neuraminidase and galactose oxidase. While the PI response was only partially suppressed by LDL with optimal suppression at 10 to 20 micrograms of protein/ml, DNA synthesis was completely suppressed although at much higher LDL concentrations, greater than 100 micrograms protein/ml. As monocyte numbers are increased, LDL suppression of DNA synthesis is decreased. The ability of NAGO to stimulate the PI response and DNA synthesis in a similar way, and the suppression of both events by LDL, suggests the PI response is important for lymphocyte activation and proliferation. Stimulation of human T lymphocytes by oxidative mitogens, neuraminidase, and galactose oxidase caused increased phosphatidylinositol metabolism and increased DNA synthesis. Both responses were suppressed by low density lipoproteins

Distribution of lymphocyte subsets in the small intestine lymphoid tissue of 1-month-old lambs.

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Corpa, J M; Juste, R A; García Marín, J F; Reyes, L E; González, J; Pérez, V

2001-04-01

Distribution of lymphocyte subpopulations along the small intestine lymphoid tissue has been examined in 1-month-old lambs using flow cytometric and immunohistochemical techniques. Monoclonal antibodies against CD4, CD8, gamma delta, CD45R and B receptors have been employed in samples from continuous ileal Peyer's patch (IPP), discrete jejunal Peyer's patches (JPP), ileocaecal valve lymphoid tissue (ICVPP), mesenteric lymph node (MLN) and intra-epithelial (IEL) and lamina propria (LPL) lymphocytes. Histological studies were also done. Differences in the lymphocyte distribution have been observed between some of the regions examined, especially between IPP and JPP for most of the markers. A remarkable feature was the existence of morphological and lymphocyte distribution differences between ICVPP and IPP, locations that had been traditionally considered as similar. The antibody against CD45R receptor used in this study, that was supposed to mark B cells and some T cells, detected cell populations located in the dome of the follicles in all the samples, whereas the centre was negative. Lymphocytes positive to the B marker employed were located mainly in the centre, suggesting that both antibodies would mark B cells in different maturation status.

The role of the B lymphocytes in endometriosis: A systematic review.

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Riccio, L G C; Baracat, E C; Chapron, C; Batteux, F; Abrão, M S

2017-09-01

The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for "endometriosis", "B cells" and "B lymphocytes" in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Lymphocyte labelling technique for the exploration of kidney transplants

International Nuclear Information System (INIS)

Guey, A.; Touraine, J.L.; Collard, M.; Claveyrolas, P.; Bouteiller, O. de; Traeger, J.

The labelling technique is developed with a precise clinical exploration in view and has to take into account the following rules or conditions: - the blood sample must be smaller than 20 ml; - the manipulation must not last more than 3 hours; - the immunological properties of the labelled lymphocytes must be kept intact; - the solution reinjected into the patient must contain no aggregates, be absolutely sterile and possess a radioactivity above 1mCi. The technique of extraction and labelling from a sample of about 15ml is described. The main factors responsible for the quality of the labelling are analysed, together with the labelling and irradiation dose effects on certain properties of the lymphocytes (viability, rosette E formation, proliferative response to mitogens) [fr

Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

International Nuclear Information System (INIS)

Lavin, M.F.; Jennings, P.A.; Hughes, D.J.

1982-01-01

Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds. (author)

B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus H; Bonnema, Steen J

2007-01-01

Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might...

DNA damage in human lymphocytes due to synergistic interaction between ionizing radiation and pesticide

International Nuclear Information System (INIS)

Kim, J. K.; Lee, K. H.; Lee, B. H.; Chun, K. J.

2001-01-01

Biological risks may arise from the possibility of the synergistic interaction between harmful factors such as ionizing radiation and pesticide. The effect of pesticide on radiation-induced DNA damage in human in human blood lymphocytes was evaluated by the single cell gel electrophoresis (SCGE) assay. The lymphocytes, with or without pretreatment of the pesticide, were exposed to 2.0 Gy of gamma ray. Significantly increased tail moment, which was a marker of DNA strand breaks in SCGE assay, showed an excellent dose-response relationship. The present study confirms that the pesticide has the cytotoxic effect on lymphocytes and that it interacts synergistically with ionizing radiationon DNA damage, as well

Simple method for culture of peripheral blood lymphocytes of Testudinidae.

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Silva, T L; Silva, M I A; Venancio, L P R; Zago, C E S; Moscheta, V A G; Lima, A V B; Vizotto, L D; Santos, J R; Bonini-Domingos, C R; Azeredo-Oliveira, M T V

2011-12-06

We developed and optimized a simple, efficient and inexpensive method for in vitro culture of peripheral blood lymphocytes from the Brazilian tortoise Chelonoidis carbonaria (Testudinidae), testing various parameters, including culture medium, mitogen concentration, mitotic index, culture volume, incubation time, and mitotic arrest. Peripheral blood samples were obtained from the costal vein of four couples. The conditions that gave a good mitotic index were lymphocytes cultured at 37°C in minimum essential medium (7.5 mL), with phytohemagglutinin as a mitogen (0.375 mL), plus streptomycin/penicillin (0.1 mL), and an incubation period of 72 h. Mitotic arrest was induced by 2-h exposure to colchicine (0.1 mL), 70 h after establishing the culture. After mitotic arrest, the cells were hypotonized with 0.075 M KCl for 2 h and fixed with methanol/acetic acid (3:1). The non-banded mitotic chromosomes were visualized by Giemsa staining. The diploid chromosome number of C. carbonaria was found to be 52 in females and males, and sex chromosomes were not observed. We were able to culture peripheral blood lymphocytes of a Brazilian tortoise in vitro, for the preparation of mitotic chromosomes.

Evaluation of four methods for separation of lymphocytes from normal individuals and patients with cancer and tuberculosis.

Science.gov (United States)

Patrick, C C; Graber, C D; Loadholt, C B

1976-01-01

An optimal technique was sought for lymphocyte recovery from normal and chronic diseased individuals. Lymphocytes were separated by four techniques: Plasmagel, Ficoll--Hypaque, a commercial semiautomatic method, and simple centrifugation using blood drawn from ten normal individuals, ten cancer patients, and ten tuberculosis patients. The lymphocyte mixture obtained after using each method was analyzed for percent recovery, amount if contamination by erythrocytes and neutrophils, and percent viability. The results show that the semiautomatic method yielded the best percent recovery of lymphocytes for normal individuals, while the simple centrifugation method contributed the highest percent recovery for cancer and tuberculosis patients. The Ficoll-Hypaque method gave the lowest erythrocyte contamination for all three types of individuals tested, while the Plasmagel method gave the lowest neutrophil contamination for all three types of individuals. The simple centrifugation method yielded all viable lymphocytes and thus gave the highest percent viability.

Failure of lymphocyte-membrane HLA-A and -B expression in two siblings with combined immunodeficiency

NARCIS (Netherlands)

Schuurman, R.K.B.; Rood, J.J. van; Vossen, J.M.; Schellekens, P.Th.A.; Feltkamp-Vroom, Th.M.; Doyer, E.; Gmelig Meyling, F.H.J.; Visser, H.K.A.

1979-01-01

A diagnosis of partial combined immunodeficiency was made in two Turkish siblings with a history of multiple pyogenic infections and persistent candidiasis. They demonstrated severe hypo-γ-globulinemia, with B-lymphocytes, but deficient plasma cell differentiation. T-Lymphocytes were decreased in

B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

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Annelieke A.A. van der Linde

2011-12-01

Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

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

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Rauf Oguzhan Kum

2015-12-01

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

Exercise Training positively modulates the Ectonucleotidase Enzymes in Lymphocytes of Metabolic Syndrome Patients.

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Martins, C C; Bagatini, M D; Cardoso, A M; Zanini, D; Abdalla, F H; Baldissarelli, J; Dalenogare, D P; Dos Santos, D L; Schetinger, M R C; Morsch, V M M

2016-11-01

In this study, we investigated the cardiovascular risk factors as well as ectonucleotidase activities in lymphocytes of metabolic syndrome (MetS) patients before and after an exercise intervention. 20 MetS patients, who performed regular concurrent exercise training for 30 weeks, 3 times/week, were studied. Anthropometric, biochemical, inflammatory and hepatic parameters and hydrolysis of adenine nucleotides and nucleoside in lymphocytes were collected from patients before and after 15 and 30 weeks of the exercise intervention as well as from participants of the control group. An increase in the hydrolysis of ATP and ADP, and a decrease in adenosine deamination in lymphocytes of MetS patients before the exercise intervention were observed (Pexercise training after 30 weeks of intervention. Additionally, exercise training reduced the inflammatory and hepatic markers to baseline levels after 30 weeks of exercise. Our results clearly indicated alteration in ectonucleotidase enzymes in lymphocytes in the MetS, whereas regular exercise training had a protective effect on the enzymatic alterations and on inflammatory and hepatic parameters, especially if it is performed regularly and for a long period. © Georg Thieme Verlag KG Stuttgart · New York.

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

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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.

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.

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

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N. V. Isaeva

2008-01-01

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

Lymphocyte respiration in children with Trisomy 21

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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.

Large granular lymphocytic leukaemia pathogenesis and management.

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Dearden, Claire

2011-02-01

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

Inhibition of murine splenic B lymphocyte activation following oral exposure to 7,12-dimethylbenz(a)anthracene (DMBA)

International Nuclear Information System (INIS)

Davis, D.P.; Burchiel, S.W.; Montano, R.M.; Seamer, L.C.

1991-01-01

Previous results from this laboratory have demonstrated that oral exposure of B6C3F1 mice to DMBA inhibited mitogen-stimulated lymphocyte activation in cells recovered from several lymphoid organs. These studies showed that both LPS and PHA-stimulated lymphocyte proliferation and PHA-induced Ca +2 mobilization were significantly inhibited by DMBA exposure, supporting the hypothesis that DMBA inhibits early events associated with lymphocyte activation. The purpose of the current studies was to test this hypothesis directly for B cell activation. B6C3F1 mice were treated with 0, 1.0, or 10 mg/kg/day doses of DMBA for 14 days (total cumulative doses of 0, 14, or 140 mg/kg). B lymphocyte populations were then selected on the flow cytometer by direct positive staining of spleen cells with phycoerythrin-labeled anti-Ly5 (B lymphocyte marker) antibodies. Ca +2 mobilization studies were performed using affinity-purified goat anti-mouse IgD antibodies as the stimulant and Indo-1 as the intracellular Ca +2 indicator. Cell proliferation studies were also performed using 3 H-thymidine and insoluble anti-IgD antibodies. Anti-IgD stimulated Ca +2 mobilization was significantly reduced at the 140 mg/kg dose of DMBA. A statistically significant decrease in anti-IgD stimulated B lymphocyte proliferation at the 14 mg/kg and 140 mg/kg doses of DMBA was found. These results suggest that B lymphocytes may be important targets for DMBA-mediated immunosuppression

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

Science.gov (United States)

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

2002-01-01

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

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents - Retention of naive T lymphocytes in HIV-infected adolescents

NARCIS (Netherlands)

Douglas, SD; Rudy, B; Muenz, L; Starr, SE; Campbell, DE; Wilson, C; Holland, C; Crowley-Nowick, P; Vermund, SH

Background: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. Objective: To assess lymphocyte subsets in HIV-infected and high-risk

The neutrophil-to-lymphocyte ratio as a marker of systemic endothelial dysfunction in asymptomatic subjects.

Science.gov (United States)

Martínez-Urbistondo, Diego; Beltrán, Almudena; Beloqui, Oscar; Huerta, Ana

2016-01-01

The neutrophil-to-lymphocyte ratio has demonstrated to be a prognostic inflammatory marker in cardiovascular disease. The objective of this study is to evaluate the association between neutrophil-to-lymphocyte ratio and pathologic urinary albumin/creatinine ratio as an early marker of cardiovascular risk and systemic endothelial dysfunction, associated with microvascular disease, in asymptomatic subjects. A unicenter cross-sectional study was conducted, including 1816 asymptomatic subjects. Patients with previous cardiovascular disease, those who were treated with ACE inhibitors and/or angiotensin II receptor blockers and patients with albumin/creatinine ratio over 300mg/g were excluded. The outcome of the study was the presence of a pathologic urinary albumin/creatinine ratio. The neutrophil-to-lymphocyte ratio was significantly associated with altered urinary albumin/creatinine ratio in the univariate analysis and after adjustment for other known endothelial and cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes or altered glomerular filtration rate). Based on the sensitivity and specificity of different neutrophil-to-lymphocyte ratio thresholds, 3 risk groups were created for altered urinary albumin/creatinine ratio: low risk in those with neutrophil-to-lymphocyte ratio 3. These groups were found to have a statistically significant and independent prognostic power for altered urinary albumin/creatinine ratio in asymptomatic patients. The neutrophil-to-lymphocyte ratio appears to be a cost-efficient, non-invasive and independent potential marker of systemic endothelial dysfunction in asymptomatic subjects. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

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Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

2011-01-13

Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

Time to and Predictors of CD4+ T-Lymphocytes Recovery in HIV-Infected Children Initiating Highly Active Antiretroviral Therapy in Ghana

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Lorna Renner

2011-01-01

Full Text Available Background. CD4+ T-lymphocyte monitoring is not routinely available in most resource-limited settings. We investigated predictors of time to CD4+ T-lymphocyte recovery in HIV-infected children on highly active antiretroviral (HAART at Korle-Bu Teaching Hospital, Ghana. Methods. Time to CD4+ T-lymphocyte recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox proportional hazard models for identifying significant predictor variables. Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age at HAART initiation was 5.5 (SD=3.1 years. The median recovery time was 60 weeks (95% CL: 55–65. Evidence at baseline of severe suppression in CD4+ T-lymphocyte count adjusted for age, age at HAART initiation, gender, and having parents alive were statistically significant in predicting time to CD4+ T-lymphocyte recovery. Conclusions. A targeted approach based on predictors of CD4+ T-lymphocyte recovery can be a viable and cost-effective way of monitoring HAART in HIV-infected children in resource-limited settings.

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

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

1977-01-01

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

Lymphocytic esophagitis: Report of three cases and review of the literature

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Jideh, Bilel; Keegan, Andrew; Weltman, Martin

2016-01-01

Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature. PMID:28035315

Heritability of Susceptibility to Ionizing Radiation-Induced Apoptosis of Human Lymphocyte Subpopulations

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Schmitz, Annette; Bayer, Jan; Dechamps, Nathalie; Goldin, Lynn; Thomas, Gilles

2007-01-01

Purpose: To evaluate the heritability of intrinsic radiosensitivity, the induction of apoptosis in lymphocyte subpopulations was determined on samples from related individuals belonging to large kindred families. Methods and Materials: Quiescent lymphocytes from 334 healthy individuals were gamma-irradiated in vitro. Apoptosis was determined 18 h after irradiation by eight-color flow cytometry. Radiosensitivity was quantified from dose-effect curves. Intrafamilial correlations and heritability were computed for 199 father-mother-offspring trios using the programs SOLAR (Sequential Oligogenic Linkage Analysis Routines) and SAGE (Statistical Analysis for Genetic Epidemiology). Segregation analyses were conducted using SAGE. Results: Marked differential susceptibility of naive and memory T lymphocytes was demonstrated. Also, although age and gender were significant covariates, their effects only accounted for a minor part of the inter-individual variation. Parent-offspring and sib-sib correlations were significant for the radiosensitivity of B cells, T4, and T8 and of effector memory T4 and T8 subpopulations. In the T4-effector memory subpopulation, the phenotype showed correlations most consistent with dominant or additive genetic effects, and the results of the segregation analysis were consistent with the contribution of a bi-allelic dominant locus. Conclusions: Heritability was demonstrated for the susceptibility to ionizing radiation-induced apoptosis of lymphocyte populations, and the segregation of the T4-effector memory radiosensitivity phenotype was consistent with a simple mendelian transmission model involving one major gene

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

International Nuclear Information System (INIS)

Countryman, P.I.; Heddle, J.A.; Crawford, E.

1977-01-01

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

LYMPHOCYTE SUBSETS AND CYTOKINES IN BLOOD AND CEREBROSPINAL FLUID IN CHILDREN WITH VIRAL AND BACTERIAL MENINGITIS

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L. A. Alekseeva

2016-01-01

Full Text Available Introduction of flow cytometry caused an increase in the investigation of liquor lymphocyte pool phenotype in the case of different brain disorders, including viral and bacterial meningitis, however this type of research in children has been relatively rare. Phenotype and lymphocyte functions are under cytokine control system, therefore detection of interconnections between lymphocyte pool subpopulation composition and cytokine level in blood and liquor of the patients concerns a great interest. The purpose of this research was to study lymphocyte subpopulation composition and the level of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ and IL-4, and also IgG in liquor and blood of children with viral and bacterial meningitis. There was performed blood and liquor investigation in 46 children aged from 1 to 16 years old with viral (n = 35 and bacterial (n = 11 meningitis. Immunophenotyping of blood and liquor cells was performed by the method of flow cytometry with the use of monoclonal antibodies to CD3, CD4, CD8, CD19, CD16, CD56, CD25 and CD95. The content of cytokines was detected in ELISA, and that of IgG — by the method of quantitative immunoturbodimetry. During an acute period of viral meningitis there was detected a decrease in NK portion and activated CD25+ cells in the blood of patients accompanied by the increase in B-lymphocytes number, along with cytokine IFNγ, IL-8 and IL-10 serum level rise. There was determined T-lymphocytes accumulation in liquor with the prevalence of CD4+ Т-cells and, to a lesser degree, CD25+ and CD95+ cells, NK and B-lymphocytes. Intrathecally there was noted the predominance of IL-6 response accompanied by the growth of IL-8 and IL-10 concentration as well. During an acute period of bacterial meningitis there was noted a decrease in percentage of CD3+, CD4+, CD8+ Т-lymphocytes, NK, CD25+ and CD95+ cells, along with, on the contrary, sharp increase in B-cells pool, simultaneously with

Apoptosis in peripheral blood lymphocytes of healthy donors and patients with laryngeal cancer after γ-irradiation in vitro

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Orlova, N.V.; Smirnova, S.G.; Zamulaeva, I.A.; Andreev, V.G.; Ryabchenko, N.I.; Saenko, A.S.

2001-01-01

Apoptosis in peripheral blood lymphocytes of healthy donors and cancer patients after γ-radiation with different doses is studied by the flow cytometry method. Wide intra- and interindividual variabilities of the lymphocyte radiosensitivity by different donors are observed. The radiosensitivity does not depend on the subpopulation composition of the lymphocyte pool. The persons with very low and high lymphocyte radiosensitivities are found significantly more often among the cancer patients than among the healthy donors. One can suggest that this method is useful to define risk groups with regard to radiogenic neoplasms and prognosis of radiotherapy efficiency [ru

CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

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M. V. Peshikova

2005-01-01

Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Early morphologic and quantitative changes in mouse peripheral blood lymphocytes after low dose gamma-irradiation

International Nuclear Information System (INIS)

Gitsov, L.; Byrneva, V.; Goranov, I.

1979-01-01

The study was undertaken in an effort to establish differences in the radiosensitivity of peripheral blood lymphocytes, as a possible test for evaluation of early and discrete radiation injury. Sexually mature mice of BAIB/c line were X-irradiated with doses of 50 and 250 rad. The animals were sacrificed by blood letting 24 hours after irradiation, but 30 minutes before this each mouse was heparinized. Smears were prepared from the enriched pooled leucocyte suspensions, obtained by dextran sedimentation of the red cells. The preparations were stained with toluidin blue by the methods of Smetana and Pappenheim. Cell size, clasmatosis, nucleolar structure and degree of cytoplasmic metachromasia were determined. It was found that the lymphocytogram of animals irradiated with 50 rad was characterized by high percentage of small lymphocytes, most of them with dispersed nuclear ribonucleoproteins and minimal clasmatose activity. Irradiation with 100 rad induced a characteristical rise in lymphocyte clasmatose activity and decrease in the number of small lymphocytes. The nucleoli were bright and well delineated. The lymphocytogram of animals irradiated with higher doses (150 and 250 rad) was characterized by predomination of large lymphocytes and hyperbasophilic forms with well preserved bright nucleoli. The percentage of lymphocates with clasmatosis was below the control value. (A.B.)

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

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

2010-04-01

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