Adult Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Hodgkin lymphoma (HL) can be cured in over 75% of new cases with combination chemotherapy and/or radiation therapy. Subtypes include classical HL (nodular sclerosis mixed-cellularity, lymphocyte depletion, and lymphocyte-rich) and nodular lymphocyte–predominant HL. Get comprehensive information on HL and treatment in this clinician summary.

Investigating Self-Control Resource Depletion as a Situational Risk Factor for Aversive Interpartner Communication by Young Adults With ADHD.

PubMed

Wymbs, Brian T

2018-06-01

Adults with attention-deficit hyperactivity disorder (ADHD) have more conflictual relations with their romantic partners than adults without ADHD. This study investigated whether adults with ADHD are differentially susceptible to conflict when self-control resources are depleted. Heterosexual adult couples (20 including at least one adult with ADHD; 12 including no adults with ADHD) were randomly assigned to have resources temporarily depleted or not. Positive and negative communication was assessed during a subsequent problem-solving task with their partners. Adults with ADHD whose self-control resources were depleted communicated less positively and more negatively with their romantic partners than adults without ADHD whose resources were depleted. Adults with ADHD appear to have a differential susceptibility to interpartner discord when their self-control resources have been depleted. Clinicians seeking to remediate discordant romantic relationships of adults with ADHD should consider evaluating how often their resources needed to manage their impulses are depleted.

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

PubMed

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

2016-11-01

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

B-lymphocyte depletion with rituximab and β-cell function: two-year results.

PubMed

Pescovitz, Mark D; Greenbaum, Carla J; Bundy, Brian; Becker, Dorothy J; Gitelman, Stephen E; Goland, Robin; Gottlieb, Peter A; Marks, Jennifer B; Moran, Antoinette; Raskin, Philip; Rodriguez, Henry; Schatz, Desmond A; Wherrett, Diane K; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S

2014-02-01

We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of β-cell function in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed further to determine whether there was persistence of effect. Eighty-seven subjects (aged 8-40 years) were randomly assigned to, and 81 received, infusions of rituximab or placebo on days 1, 8, 15, and 22. The primary outcome-baseline-adjusted mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 1 year-showed higher C-peptide AUC with rituximab versus placebo. Subjects were further followed with additional MMTTs every 6 months. The rate of decline of C-peptide was parallel between groups but shifted by 8.2 months in rituximab-treated subjects. Over 30 months, AUC, insulin dose, and HbA1c were similar for rituximab and placebo. However, in evaluating change in C-peptide over the entire follow-up period, the rituximab group means were significantly larger as compared within assessment times with the placebo group means using a global test (P = 0.03). Odds ratio for loss of C-peptide to <0.2 nmol/L following rituximab was 0.565 (P = 0.064). B-lymphocytes recovered to baseline values by 18 months. Serum IgG levels were maintained in the normal range but IgM levels were depressed. Like several other immunotherapeutic approaches tested, in recent-onset T1DM, rituximab delays the fall in C-peptide but does not appear to fundamentally alter the underlying pathophysiology of the disease.

Identification of canine T lymphocytes by membrane receptor to peanut agglutinin: T-lymphocyte identification in dogs with lupus-like syndrome.

PubMed

Rigal, D; Bendali-Ahcène, S; Monier, J C; Mohana, K; Fournel, C

1983-09-01

Canine T lymphocytes were detected, using fluorescent peanut agglutinin (PNA) as a marker. Using a fluorescent technique and cytofluorometry, 70 +/- 11% and 72.4%, respectively, of peripheral blood lymphocytes were bound to PNA. Of thymocytes, 97 +/- 4.5% were detected by fluorescent PNA, but less than 1% were detected for lymphocytes from bone marrow. The T-lymphocyte depletion and enrichment indicated that PNA was bound to lymphocytes recognized by anti-T-lymphocyte heterologous serum. A T-lymphocyte deficiency was detected among 8 dogs with a lupus-like syndrome.

THE FREQUENCY OF T(14;18) IN BLOOD LYMPHOCYTES IS STABLE OVER A 2 YEAR PERIOD IN ADULTS

EPA Science Inventory

The Frequency of t(14;18) in Blood Lymphocytes Is Stable over a 2 Year Period in Adults

As part of a multi-endpoint molecular epidemiology study on in utero environmental exposures, umbilical cord and adult blood lymphocytes were examined for the frequency of t(14;18) by ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, S.M.; Linette, G.P.; Doughty, B.L.

1987-08-01

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

Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

ClinicalTrials.gov

2013-06-03

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

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

ClinicalTrials.gov

2018-04-02

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

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

PubMed

Knop, J

1980-12-01

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

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

PubMed

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

2013-10-01

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

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

PubMed Central

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

2009-01-01

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

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

ClinicalTrials.gov

2015-02-10

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

Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions.

PubMed

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.

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

ERIC Educational Resources Information Center

Leighton, Jacqueline P.; Bisanz, Gay L.

2003-01-01

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

The Toxicity of Depleted Uranium

PubMed Central

Briner, Wayne

2010-01-01

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

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

ClinicalTrials.gov

2017-10-11

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

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

ClinicalTrials.gov

2018-02-01

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

Colony formation by normal and malignant human B-lymphocytes.

PubMed Central

Izaguirre, C. A.; Minden, M. D.; Howatson, A. F.; McCulloch, E. A.

1980-01-01

A method is described that permits colony formation in culture by B lymphocytes from normal blood and from blood, marrow or lymph nodes of patients with myeloma or lymphoma. The method depends on: (1) exhaustively depleting cell suspensions of T lymphocytes, (2) a medium conditioned by T lymphocytes in the presence of phytohaemagglutinin (PHA-TCM), and (3) irradiated autologous or homologous T lymphocytes. Under these conditions the assay is linear. Cellular development of B lymphocytes can be followed; differentiation to plasma cells is seen in cultures of cells from normal individuals and myeloma patients, but not lymphoma patients. Malignant B lymphocytes in culture produced immunoglobulin of the class identified in the patient's blood, or in freshly obtained cells. We conclude that the assay is suitable for studying the growth, differentiation and regulation of normal and malignant B lymphocytes in culture. Images Fig. 1 Fig. 2 PMID:6968572

Effect of immunodepletion of MHC class II-positive cells from pancreatic islets on generation of cytotoxic T-lymphocytes in mixed islet-lymphocyte coculture.

PubMed

Stock, P G; Ascher, N L; Platt, J L; Kaufman, D B; Chen, S; Field, M J; Sutherland, D E

1989-01-01

In vitro manipulation of pancreatic islets to decrease islet immunogenicity before transplantation has largely been directed at eliminating the major histocompatibility complex (MHC) class II-positive passenger leukocytes from the islets. The mixed islet-lymphocyte coculture (MILC) system was used to quantitate the efficacy of immunodepletion of MHC class II-positive cells from pancreatic islets in terms of reducing immunogenicity. With these experiments we compared the in vitro immunogenicity of MHC class II-depleted islets with untreated islets. B10.BR (H-2k) islets were treated with anti-Iak alloserum followed by complement. This treatment successfully eliminated MHC class II-positive cells from the islets, as demonstrated by indirect immunofluorescence techniques. Depleted islets generated slightly lower amounts of allospecific cytotoxic T-lymphocyte (CTL) activity when exposed to C57BL/6 (H-2b) splenocytes in the MILC than untreated control islets. Although the amount of CTL generated by the depleted islets was slightly less than that generated by untreated islets, there was significant stimulation of CTL by the MHC class II-depleted islets. Therefore, the presence or absence of MHC class II cells within the islet is unlikely to be the decisive factor contributing to islet immunogenicity.

Graft-versus-leukemia effects of transplantation and donor lymphocytes.

PubMed

Kolb, Hans-Jochem

2008-12-01

Allogeneic transplantation of hematopoietic cells is an effective treatment of leukemia, even in advanced stages. Allogeneic lymphocytes produce a strong graft-versus-leukemia (GVL) effect, but the beneficial effect is limited by graft-versus-host disease (GVHD). Depletion of T cells abrogates GVHD and GVL effects. Delayed transfusion of donor lymphocytes into chimeras after T cell-depleted stem cell transplantation produces a GVL effect without necessarily producing GVHD. Chimerism and tolerance provide a platform for immunotherapy using donor lymphocytes. The allogeneic GVL effects vary from one disease to another, the stage of the disease, donor histocompatibility, the degree of chimerism, and additional treatment. Immunosuppressive therapy before donor lymphocyte transfusions may augment the effect as well as concomitant cytokine treatment. Possible target antigens are histocompatibility antigens and tumor-associated antigens. Immune escape of tumor cells and changes in the reactivity of T cells are to be considered. Durable responses may be the result of the elimination of leukemia stem cells or the establishment of a durable immune control on their progeny. Recently, we have learned from adoptive immunotherapy of viral diseases and HLA-haploidentical stem cell transplantation that T-cell memory may be essential for the effective treatment of leukemia and other malignancies.

General Information about Chronic Lymphocytic Leukemia

MedlinePlus

... Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Effects of in vivo hydrocortisone on lymphocyte-mediated cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, P.; Zaytoun, A.M.; Lee, J.H. Jr.

To examine the effects of in vivo hydrocortisone sodium succinate (HC) on natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC), 11 normal adults received a single intravenous bolus of 400 mg hydrocortisone. Lymphocytes were tested for NK activity and ADCC using 51chromium (51Cr)-release and single cell cytotoxicity assays against Molt-4 and sensitized RL O leads to target cells, respectively. Four hours after injection, both NK and ADCC activity were transiently increased in the 51Cr-release system. At 4 hours, there was a twofold increase in the relative frequency of potentially cytotoxic target binding cells but the absolute number of thesemore » cells did not change. However, the percentage lysis of bound targets at 4 hours was not altered. These data suggest that: 1) lymphocytes participating in NK and ADCC reactions are refractory to the kinetic and functional effects of HC; 2) the increased lytic activity observed at 4 hours is due to a selective depletion of noncytotoxic cells from the circulation; and 3) NK and ADCC activity did not differ in their responses to HC.« less

Lymphocyte and neuronal antigens in neuropsychiatric lupus: presence of an elutable, immunoprecipitable lymphocyte/neuronal 52 kd reactivity.

PubMed Central

Denburg, J A; Behmann, S A

1994-01-01

OBJECTIVE--To examine specific lymphocyte or neuronal antigens immuno-precipitated by systemic lupus erythematosus (SLE) sera. METHOD--SLE sera were screened for the presence of antibodies binding to surface antigens of CD4(+) HUT-78 or SK-N-SH and IMR-6 neuroblastoma cells using Western blotting or radioimmunoprecipitation. RESULTS--IgG eluates from both lymphocytes and neuroblastoma cells recognised a 52 kd band in HUT 78 cell lysates. Eight sera studied further using radioimmunoprecipitation also demonstrated binding to a 52 kd antigen (4/8 on HUT-78, 8/8 on SK-N-SH cells), partially depleted by absorption with viable HUT-78. CONCLUSION--A 52 kd antigen recognised by SLE sera on lymphocytes and neuronal cells may play a role in the pathogenesis of neuropsychiatric-SLE. Images PMID:8017983

The Effect of In Vivo Hydrocortisone on Subpopulations of Human Lymphocytes

PubMed Central

Fauci, Anthony S.; Dale, David C.

1974-01-01

This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg or 400 mg of hydrocortisone, and blood was drawn at hourly intervals for 6 h, and then again at 10 and 24 h after injection. Profound decreases in absolute numbers of circulating lymphocytes and monocytes occurred at 4-6 h after both 100 mg and 400 mg of hydrocortisone. Counts returned to normal by 24 h. The relative proportion of circulating thymus-derived lymphocytes as measured by the sheep red blood cell rosette assay decreased maximally by 4 h and returned to base line 24 h after hydrocortisone. There was a selective depletion of functional subpopulations of lymphocytes as represented by differential effects on in vitro stimulation with various mitogens and antigens. Phytohaemagglutinin response was relatively unaffected, while responses to concanavalin A were significantly diminished. Responses to pokeweed mitogen were unaffected by 100 mg of hydrocortisone, but greatly diminished by 400 mg of hydrocortisone. In vitro responses to the antigens streptokinase-streptodornase and tetanus toxoid were markedly diminished by in vivo hydrocortisone. Reconstitution of monocyte-depleted cultures with autologous monocytes partially corrected the diminished response to antigens. This transient selective depletion of monocytes and subsets of human lymphocytes by a single dose of hydrocortisone is most compatible with a redistribution of these cells out of the circulation into other body compartments. Images PMID:4808638

Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

NASA Astrophysics Data System (ADS)

Shi, Yufang

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

CD8+ lymphocytes are required to maintain virus suppression in SIV-infected macaques treated with short-term antiretroviral therapy

PubMed Central

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

2016-01-01

Infection with HIV persists despite suppressive antiretroviral therapy (ART) and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows these cells contribute to virus control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining virus suppression under ART remains unknown. We showed that in SIV-infected RMs treated with short-term ART (i.e., 8-32 weeks), depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals, and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells pre-depletion positively correlated with both peak and area-under-the-curve of viremia post-depletion. These results suggest a role for CD8+ T cells in controlling virus production during ART, thus providing rationale to explore immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID:27653601

Distinct Phenotype, Longitudinal Changes of Numbers and Cell-Associated Virus in Blood Dendritic Cells in SIV-Infected CD8-Lymphocyte Depleted Macaques

PubMed Central

Soulas, Caroline; Autissier, Patrick J.; Burdo, Tricia H.; Lifson, Jeffrey D.; Williams, Kenneth C.

2015-01-01

Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs) during HIV infection is well established. However, changes of myeloid DCs (mDCs) are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs. PMID:25915601

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

PubMed

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

2011-10-01

The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 × 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15 d adaptation period preceded a 5 d total collection of faeces for the digestibility trial. On day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0.15, 0.30 and 0.45 % of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P < 0.05). No evidence of a difference in faecal bacteria counts between ages was found (total aerobes, total anaerobes, Bifidobacterium, Lactobacillus, Clostridium and Escherichia coli: P>0.15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P ≤ 0.05) and faecal pH was higher (P = 0.03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P ≤ 0.01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-04-15

Canaria Hair Breed (CHB) sheep display resistance against the adult stage of the nematode, Haemonchus contortus. Previous studies have suggested significant correlations between γδ + T lymphocytes and fecundity of female adult worms, suggesting a novel role in immune modulation by these cells. The largest proportion of γδ + T lymphocytes in sheep are the subpopulation of γδ + /WC1 + T cells. The aim of this study was to evaluate the effect of γδ + ⁄WC1 + T cell depletion via infusion of anti-γδ/WC1 monoclonal antibody (mAb) on the subsequent immune response of CHB sheep infected with H. contortus. Significantly lower γδ + T cell levels in both peripheral blood and in the basal layers of the abomasal tissue resulted following anti-γδ/WC1 mAb infusion of CHB sheep compared to control animals. Worms recovered from the anti-γδ/WC1 mAb treated CHB sheep had significantly longer female worms with correspondingly more eggs in utero than the saline control group. Significant correlations between eosinophils and worm length and fecundity were no longer apparent in the anti-γδ/WC1 mAb treated CHB sheep. These results support the notion that γδ + T cells in CHB sheep play a critical role in fecundity regulation (length and eggs in utero) of H. contortus adult female worms, and highlights a new mechanism of modulation by this lymphocyte population, possibly involving eosinophil activation. Copyright © 2017 Elsevier B.V. All rights reserved.

CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.

PubMed

Klatt, Nichole R; Shudo, Emi; Ortiz, Alex M; Engram, Jessica C; Paiardini, Mirko; Lawson, Benton; Miller, Michael D; Else, James; Pandrea, Ivona; Estes, Jacob D; Apetrei, Cristian; Schmitz, Joern E; Ribeiro, Ruy M; Perelson, Alan S; Silvestri, Guido

2010-01-29

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

PubMed Central

Klatt, Nichole R.; Shudo, Emi; Ortiz, Alex M.; Engram, Jessica C.; Paiardini, Mirko; Lawson, Benton; Miller, Michael D.; Else, James; Pandrea, Ivona; Estes, Jacob D.; Apetrei, Cristian; Schmitz, Joern E.; Ribeiro, Ruy M.; Perelson, Alan S.; Silvestri, Guido

2010-01-01

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication. PMID:20126441

Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells.

PubMed

Ceronie, Bryan; Jacobs, Benjamin M; Baker, David; Dubuisson, Nicolas; Mao, Zhifeng; Ammoscato, Francesca; Lock, Helen; Longhurst, Hilary J; Giovannoni, Gavin; Schmierer, Klaus

2018-05-01

The mechanism of action of oral cladribine, recently licensed for relapsing multiple sclerosis, is unknown. To determine whether cladribine depletes memory B cells consistent with our recent hypothesis that effective, disease-modifying treatments act by physical/functional depletion of memory B cells. A cross-sectional study examined 40 people with multiple sclerosis at the end of the first cycle of alemtuzumab or injectable cladribine. The relative proportions and absolute numbers of peripheral blood B lymphocyte subsets were measured using flow cytometry. Cell-subtype expression of genes involved in cladribine metabolism was examined from data in public repositories. Cladribine markedly depleted class-switched and unswitched memory B cells to levels comparable with alemtuzumab, but without the associated initial lymphopenia. CD3 + T cell depletion was modest. The mRNA expression of metabolism genes varied between lymphocyte subsets. A high ratio of deoxycytidine kinase to group I cytosolic 5' nucleotidase expression was present in B cells and was particularly high in mature, memory and notably germinal centre B cells, but not plasma cells. Selective B cell cytotoxicity coupled with slow repopulation kinetics results in long-term, memory B cell depletion by cladribine. These may offer a new target, possibly with potential biomarker activity, for future drug development.

Reference values of lymphocyte sub-populations in healthy human immunodeficiency virus-negative Iranian adults.

PubMed

Kamallou, Atefeh; Haji Abdolbaghi, Mahbobeh; Mohraz, Minoo; Rasolinejad, Mernaz; Karbasi, Ehsan; Ansaripour, Bita; Soltani, Samaneh; Rezaei, Arezou; Khalili, Neda; Amirzargar, Aliakbar

2014-12-01

Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory findings, reference intervals must be determined in every population. To establish a normal reference range for CD3+, CD4+, CD8+, CD19+ and CD56+ lymphocytes in a healthy Iranian adult population using flowcytometry. Blood samples were collected from 221 HIV seronegative individuals, including 112 females and 109 males, with ages ranging from 20 to 40 years old. The percentage of lymphocytes expressing either of CD3, CD4, CD8, CD19 and CD56 surface markers were determined by flowcytometry assay. Total mean percentage and absolute count of lymphocyte subsets were as follows: CD3+: 70.90 ± 7.54%, 1800.87 ± 471.09 cells/µl; CD4+: 41.04 ± 7.86%, 1039.99 ± 338.02 cells/µl; CD8+: 31.11 ± 6.60%, 783.95 ± 234.87 cells/µl; CD19+: 12.77 ± 4.56%, 328.37 ± 153.17 cells/µl; CD56+: 15.53 ± 6.34%, 388.62 ± 176.17 cells/µl, respectively. The ratio of CD4+/CD8+ lymphocytes for the studied population was 1.39 ± 0.48. Significant differences were observed between male and female subjects indicating that the average percentage of CD3+ cells (p=0.017) and CD4+ T cells (p=0.003) were higher in the female population, whereas the average percentage of CD19+ cells (p=0.02) tended to be higher among males. However, investigations on the CD56+ NK cell and CD8+ T cell sub-populations did not show any statistical differences between the two genders. In comparison with reports of other populations, we were confronted with different results. Establishing reference values of lymphocyte subsets for each population is helpful in achieving standard criteria for the prognosis of HIV infection. Therefore, normal ranges established by this survey can be used as a reference for decisions made in

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

PubMed

Truskaite, Kotryna; Dlugosz, Aldona

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis

PubMed Central

Wang, Guohao; Liu, Xudong; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

2016-01-01

The Huntington’s disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutant HTT is an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducible Htt knockout mice, we found that Htt depletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depleting Htt in neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenic HTT can rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment. PMID:26951659

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-10-01

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

Lymphocytosis (High Lymphocyte Count)

MedlinePlus

... to be lymphocytosis in adults. In children, the threshold for lymphocytosis varies with age. It may be ... as 9,000 lymphocytes per microliter. The exact thresholds for lymphocytosis may vary slightly from one lab ...

Percentage of Memory B Lymphocytes and Regulatory T Lymphocytes in Peripheral Blood are Low but Not Predictive of Therapy outcomes in Newly Diagnosed Adult Patients with Primary Immune Thrombocytopenia.

PubMed

Yilmaz, Mustafa; Ayhan, Semiha

2017-12-01

Although changes in the number and function of regulatory T lymphocytes have been reported in primary immune thrombocytopenia (ITP), no study has investigated whether quantification of these cell types in peripheral blood could be used as early predictive marker of treatment outcome. And, it is not clear whether any change occurs in peripheral blood memory B lymphocyte levels in ITP. Hence, the aim of this study was to investigate the percentage of regulatory T lymphocytes and memory B lymphocytes in peripheral blood of ITP patients compared to controls, and also examine whether these levels have any significant predictive value for therapy outcome. A total of 20 newly diagnosed, untreated patients with ITP and 20 healthy controls were included. Flow cytometric analyses of lymphocyte subtypes in the peripheral blood were performed in specimens obtained from patients at the time of diagnosis and one month after the therapy initiation. First line corticosteroid (1 mg/kg/day methylprednisolone) therapy or splenectomy as second line treatment was performed, and patients were followed up for 3 years. Percentage of regulatory T lymphocytes (0.25 ± 0.17% vs. 1.14 ± 0.77%, P  < 0.0001, n = 20) and percentage of memory B lymphocytes (1.57 ± 1.24% vs. 4.38 ± 2.41%, P  < 0.001, n = 20) was significantly lower in ITP patients than healthy controls, at baseline. After one month therapy, the percentage of memory B lymphocytes of ITP patients significantly increased (from 1.66 ± 1.31% to 3.0 ± 1.7%, P  < 0.009, n = 17). The initial value of regulatory T (0.33 ± 0.30%, n = 10 vs. 0.16 ± 0.05%, n = 7, P  > 0.05) and memory B lymphocytes percentages (2.1 ± 1.8%, n = 10 vs. 1.1 ± 0.75%, n = 7, P  > 0.05) were not significantly different for those who had complete response to first line therapy than those required splenectomy. These results indicate that regulatory T lymphocytes and memory B lymphocytes percentages are not

No detectable effects of acute tryptophan depletion on short-term immune system cytokine levels in healthy adults.

PubMed

Hildebrandt, Caroline S; Helmbold, Katrin; Linden, Maike; Langen, Karl-Josef; Filss, C P; Runions, Kevin C; Stewart, Richard M; Rao, Pradeep; Moore, Julie K; Mahfouda, Simone; Morandini, Hugo A E; Wong, Janice W Y; Rink, Lothar; Zepf, Florian D

2018-04-26

Recent research suggested an influence of diminished central nervous serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in healthy adult females. However, studies assessing immunological parameters in combination with dietary challenge techniques that impact brain 5-HT synthesis in humans are lacking.  Methods: In the present trial, a pilot analysis was conducted on data obtained in healthy adult humans receiving either different dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced control conditions (BAL) to study the effects of reduced central nervous 5-HT synthesis on serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 concentrations. The data of N = 35 healthy adults were analysed who were randomly subjected to one of the following two dietary conditions in a double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations for the assessment of relevant parameters (TNF-α, IL-1β and IL-6) and relevant TRP-related characteristics after the respective challenge procedures were assessed at baseline (T0) and in hourly intervals after administration over a period of 6 h (T1-T6).  Results: The ATD condition did not result in significant changes to cytokine concentrations for the entire study sample, or in male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion appears to have no statistically significant short-term impact on cytokine concentrations in healthy adults.  Conclusions: Future research on immunological stressors in combination with challenge techniques will be of value in order to further disentangle the complex interplay between brain 5-HT synthesis and immunological pathways.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yachie, A.; Tosato, G.; Straus, S.E.

1985-08-01

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

CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

ClinicalTrials.gov

2017-12-20

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

Lymphocyte apheresis for chimeric antigen receptor T-cell manufacturing in children and young adults with leukemia and neuroblastoma.

PubMed

Ceppi, Francesco; Rivers, Julie; Annesley, Colleen; Pinto, Navin; Park, Julie R; Lindgren, Catherine; Mgebroff, Stephanie; Linn, Naomi; Delaney, Meghan; Gardner, Rebecca A

2018-06-01

The first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T-cell manufacturing in pediatric and young adult patients with leukemia, non-Hodgkin lymphoma, or neuroblastoma. Apheresis procedures were performed on a COBE Spectra machine using the mononuclear cell program, with a collection target of 1 × 10 9 total mononuclear cells per kilogram. Data were collected regarding preapheresis and postapheresis blood counts, apheresis parameters, products, and adverse events. Ninety-nine patients (ages 1.3-25.7 years) and 102 apheresis events were available for analysis. Patients underwent apheresis at a variety of absolute lymphocyte cell counts, with a median absolute lymphocyte count of 944 cells/μL (range, 142-6944 cells/μL). Twenty-two patients (21.6%) had absolute lymphocyte counts less than 500 cells/μL. The mononuclear cell target was obtained in 100% of all apheresis harvests, and chimeric antigen receptor T-cell production was possible from the majority of collections (94%). Mononuclear cell collection efficiency was 65.4%, and T-lymphocyte collection efficiency was 83.4%. Ten patients (9.8%) presented with minor adverse events during the 102 apheresis procedures, with one exception of a severe allergy. Mononuclear cell apheresis for chimeric antigen receptor T-cell therapy is well tolerated and safe, and it is possible to obtain an adequate quantity of CD3+ lymphocytes for chimeric antigen receptor T-cell manufacturing in heavily pretreated patients who have low lymphocyte counts. © 2018 AABB.

Detection of adult T-cell leukemia virus (ATLV) bearing lymphocytes in concentrated red blood cells derived from ATL associated antibody (ATLA-Ab) positive donors.

PubMed

Morishima, Y; Ohya, K; Ueda, R; Fukuda, T

1986-01-01

Adult T cell leukemia associated antibody (ATLA-Ab) positive persons were screened by indirect immunofluorescence (IF) testing. Their lymphocytes were collected from concentrated red blood cells (CRC), and cultured in vitro with and without phytohemagglutinin (PHA) for 10 days. The expression of ATL virus (ATLV) positive lymphocytes during the in vitro culture was then analyzed by IF assay using mouse monoclonal antibody ATL-19 reactive to p19 core protein of ATLV. 97% of ATLA-Ab positive CRC (36 cases) demonstrated ATLV positive lymphocytes after being cultured for more than 10 days with PHA, whereas, none of ATLA-Ab negative CRC (22 cases) demonstrated ATLV positive lymphocytes. All of the 10 ATLA-Ab positive CRC that were stored for 2, 4, and 7 days contained lymphocytes which expressed ATLV after in vitro culture, while 7 of 10 CRC stored for 14 days and only 1 of 10 CRCs stored for 20 days, expressed ATLV positive lymphocytes. This data indicates that almost all of the ATLA-Ab positive blood contained ATLV positive lymphocytes, and that the in vitro appearance of these ATLV positive lymphocytes was reduced by storing the CRC for more than 14 days.

A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults.

PubMed

Oka, Saori; Hirai, Jun; Yasukawa, Takashi; Nakahara, Yasuyuki; Inoue, Yoshihiro H

2015-08-01

The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS accumulation by depletion of Cu/Zn-SOD (SOD1) or Mn-SOD (SOD2) influenced age-related impairment of the nervous system and muscles in Drosophila. We confirmed the efficient depletion of Sod1 and Sod2 through RNAi and ROS accumulation by monitoring of ROS-inducible gene expression. Both RNAi flies displayed accelerated impairment of locomotor activity with age and shortened lifespan. Similarly, adults with nervous system-specific depletion of Sod1 or Sod2 also showed reduced lifespan. We then found an accelerated loss of dopaminergic neurons in the flies with suppressed SOD expression. A half-dose reduction of three pro-apoptotic genes resulted in a significant suppression of the neuronal loss, suggesting that apoptosis was involved in the neuronal loss caused by SOD silencing. In addition, depletion of Sod1 or Sod2 in musculature is also associated with enhancement of age-related locomotion impairment. In indirect flight muscles from SOD-depleted adults, abnormal protein aggregates containing poly-ubiquitin accumulated at an early adult stage and continued to increase as the flies aged. Most of these protein aggregates were observed between myofibril layers. Moreover, immuno-electron microscopy indicated that the aggregates were predominantly localized in damaged mitochondria. These findings suggest that muscular and neuronal ROS accumulation may have a significant effect on age-dependent impairment of the Drosophila adults.

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

ClinicalTrials.gov

2015-09-27

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

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

ClinicalTrials.gov

2017-07-24

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

Adult cases of mitochondrial DNA depletion due to TK2 defect: an expanding spectrum.

PubMed

Béhin, A; Jardel, C; Claeys, K G; Fagart, J; Louha, M; Romero, N B; Laforêt, P; Eymard, B; Lombès, A

2012-02-28

In this study we aim to demonstrate the occurrence of adult forms of TK2 mutations causing progressive mitochondrial myopathy with significant muscle mitochondrial DNA (mtDNA) depletion. Patients' investigations included serum creatine kinase, blood lactate, electromyographic, echocardiographic, and functional respiratory analyses as well as TK2 gene sequencing and TK2 activity measurement. Mitochondrial activities and mtDNA were analyzed in the patients' muscle biopsy. The 3 adult patients with TK2 mutations presented with slowly progressive myopathy compatible with a fairly normal life during decades. Apart from its much slower progression, these patients' phenotype closely resembled that of pediatric cases including early onset, absence of CNS symptoms, generalized muscle weakness predominating on axial and proximal muscles but affecting facial, ocular, and respiratory muscles, typical mitochondrial myopathy with a mosaic pattern of COX-negative and ragged-red fibers, combined mtDNA-dependent respiratory complexes deficiency and mtDNA depletion. In accordance with the disease's relatively slow progression, the residual mtDNA content was higher than that observed in pediatric cases. That difference was not explained by the type of the TK2 mutations or by the residual TK2 activity. TK2 mutations can cause mitochondrial myopathy with a slow progression. Comparison of patients with similar mutations but different disease progression might address potential mechanisms of mtDNA maintenance modulation.

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

NASA Astrophysics Data System (ADS)

Leighton, Jacqueline P.; Bisanz, Gay L.

2003-01-01

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

Interleukin-2-dependent long-term cultures of low-density lymphocytes allow the proliferation of lymphokine-activated killer cells with natural killer, Ti gamma/delta or TNK phenotype.

PubMed

Testa, U; Care, A; Montesoro, E; Fossati, C; Giannella, G; Masciulli, R; Fagioli, M; Bulgarini, D; Habetswallner, D; Isacchi, G

1990-01-01

We have developed a culture system for "long-term" growth of human lymphokine-activated killer (LAK) cells exhibiting an elevated, wide-spectrum antitumor cytotoxicity. The system allows the exponential growth of monocyte-depleted low-density lymphocytes in the presence of human serum and recombinant human interleukin-2 (10(3) U/ml), alone or in combination with interleukin-1 alpha or beta (both at 10 U/ml). Eighteen cultures were established from 18 normal adult donors. The membrane phenotypes of the final LAK cell population, assessed by a panel of monoclonal antibodies (mAb), consist of three main types: (a) NKH-1+, Ti alpha/beta-, Ti gamma/delta-, and CD3- lymphocytes; (b) NKH-1+, Ti alpha/beta-, Ti gamma/delta+, and CD3+ lymphocytes and (c) NKH-1+, Ti alpha/beta+, Ti gamma/delta- and CD3+ lymphocytes. Northern blot analysis showed that all these cell populations express relatively high levels of perforin RNA, particularly cells exhibiting the first phenotype. This culture system may provide a tool for cellular and molecular studies on the mechanisms of antitumor cytotoxicity, as well as the basis for new adoptive immunotherapy protocols in advanced center.

CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2014-05-07

B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Malignant Neoplasm; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

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

ERIC Educational Resources Information Center

And Others; Hann, Hie-Won L.

1979-01-01

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

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

ClinicalTrials.gov

2017-02-21

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

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

PubMed

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

2015-01-01

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

Reference ranges of lymphocyte subsets balanced for age and gender from a population of healthy adults in Chongqing District of China.

PubMed

Zhang, Kejun; Wang, Feng; Zhang, Mingxu; Cao, Xinglu; Yang, Shaojun; Jia, Shuangrong; Wang, Lixin; Luo, Jie; Deng, Shaoli; Chen, Ming

2016-11-01

The enumeration of lymphocyte subsets plays an essential role in the monitoring of immunological disorders. Immunophenotyping values have been found to be influenced by race, age, gender, and environmental conditions. Therefore, it is important to establish reference ranges for healthy adults from the local population for clinical decision-making. The current study aimed to establish a normal reference range for peripheral blood lymphocyte subsets in healthy adults from the Chongqing District of China by using single-platform flow cytometry. Age- and gender-specific reference ranges were established in 268 healthy adult males and females between 21 and 60 years of age. The CD8+ cell counts decreased with age, CD4+ cell percentages and counts increased with age, and total T cell percentages were higher in the female population. Our results are similar to those reported from other parts of China but different from some results reported from other countries; this further stresses the need to establish local reference ranges by region. Our results will help in the management of patients with human immunodeficiency virus and other immunological disorders in Chongqing District. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

Deplete! Deplete! Deplete!

NASA Astrophysics Data System (ADS)

Woodson, J.

2017-12-01

Deplete is intended to demonstrate by analogy the harmful effect that Green House Gases (GHG's) such as CO2 and H2O vapor are causing to the Ozone Layer. Increasing temperatures from human activities are contributing to the depletion of Ozone.

Clofarabine in Adult Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-02-04

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

Modification of lymphocyte responsiveness in vitro by lambda carrageenan compared with colloidal silica and depletion of surface adherent cells.

PubMed Central

Pawelec, G; Brons, G

1978-01-01

The effects of the immunosuppressive sulphated polygalactan lambda carrageenan on in vitro models of allograft immunity were compared with the effects of removing macrophages (surface adherent and/or phagocytic cells) by established methods. Carrageenan depressed the primary mixed lymphocyte reactions, but not to the same extent as the removal of macrophages. 2-Mercaptoethanol restored the response. Secondary mixed lymphocyte reactions and responses to phytohaemaglutinin were depressed by carrageenan but not by the removal of macrophages, and in these systems 2-mercaptoethanol failed to restore the responses of carrageenan-treated cultures. In contrast, cell-mediated cytolysis by presensitized lymphocytes was not affected by carrageenan or by colloidal silica. Carrageenan depressed cell-mediated cytolysis only if it was present during the sensitization of the effector cells. We conclude that carrageenan can have two dose-related effects in vitro: one on the macrophage and one on the responding lymphocyte. PMID:207475

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

MedlinePlus

... Impact Support LRF Subscribe About Lymphoma Chronic Lymphocytic Leukemia Home » About Lymphoma » Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Chronic lymphocytic leukemia Disease generally ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.more » 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.« less

Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

PubMed

Johnson, B J; Bruno, J P

1995-02-01

A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

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

PubMed

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

2017-03-01

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

Failure to replicate depletion of self-control.

PubMed

Xu, Xiaomeng; Demos, Kathryn E; Leahey, Tricia M; Hart, Chantelle N; Trautvetter, Jennifer; Coward, Pamela; Middleton, Kathryn R; Wing, Rena R

2014-01-01

The limited resource or strength model of self-control posits that the use of self-regulatory resources leads to depletion and poorer performance on subsequent self-control tasks. We conducted four studies (two with community samples, two with young adult samples) utilizing a frequently used depletion procedure (crossing out letters protocol) and the two most frequently used dependent measures of self-control (handgrip perseverance and modified Stroop). In each study, participants completed a baseline self-control measure, a depletion or control task (randomized), and then the same measure of self-control a second time. There was no evidence for significant depletion effects in any of these four studies. The null results obtained in four attempts to replicate using strong methodological approaches may indicate that depletion has more limited effects than implied by prior publications. We encourage further efforts to replicate depletion (particularly among community samples) with full disclosure of positive and negative results.

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

NASA Technical Reports Server (NTRS)

Rubin, A. L.

1977-01-01

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

CD4+ T cells are required to contain early extrathoracic TB dissemination and sustain multi-effector functions of CD8+ T and CD3− lymphocytes

PubMed Central

Yao, Shuyu; Huang, Dan; Chen, Crystal Y.; Halliday, Lisa; Wang, Richard C.; Chen, Zheng W.

2014-01-01

The possibility that CD4+ T cells can act as “innate-like” cells to contain very-early M. tuberculosis (Mtb) dissemination and function as master helpers to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes during development of adaptive immunity against primary tuberculosis(TB) has not been demonstrated. We showed that pulmonary Mtb infection of CD4-depleted macaques surprisingly led to very-early extrathoracic Mtb dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. CD4 depletion during Mtb infection revealed the ability of CD8+ T cells to compensate and rapidly differentiate to Th17-like/Th1-like, and cytotoxic-like effectors, but these effector functions were subsequently unsustainable due to CD4 deficiency. While CD3-negative non-T lymphocytes in presence of CD4+ T cells developed predominant Th22-like and NK-like (perforin production) responses to Mtb infection, CD4 depletion abrogated these Th22-/NK-like effector functions and favored IL-17 production by CD3-negative lymphocytes. CD4-depleted macaques exhibited no or few pulmonary T effector cells constitutively producing IFN-γ, TNFα, IL-17, IL-22, and perforin at the endpoint of more severe TB, but presented pulmonary IL-4+ T effectors. TB granulomas in CD4-depleted macaques contained fewer IL-22+ and perforin+ cells despite presence of IL-17+ and IL-4+ cells. These results implicate previously-unknown “innate-like” ability of CD4+ T cells to contain extrathoracic Mtb dissemination at very early stage. Data also suggest that CD4+ T cells are required to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes and to prevent rapid TB progression during Mtb infection of nonhuman primates. PMID:24489088

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

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Baldwin, Kenneth M.

1995-01-01

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

Chlamydophila pneumoniae in human immortal Jurkat cells and primary lymphocytes uncontrolled by interferon-γ.

PubMed

Ishida, Kasumi; Kubo, Takeru; Saeki, Ayumi; Yamane, Chikayo; Matsuo, Junji; Yimin; Nakamura, Shinji; Hayashi, Yasuhiro; Kunichika, Miyuki; Yoshida, Mitsutaka; Takahashi, Kaori; Hirai, Itaru; Yamamoto, Yoshimasa; Shibata, Ken-ichiro; Yamaguchi, Hiroyuki

2013-03-01

Lymphocytes are a potential host cell for Chlamydophila pneumoniae, although why the bacteria must hide in lymphocytes remains unknown. Meanwhile, interferon (IFN)-γ is a crucial factor for eliminating chlamydiae from infected cells through indoleamine 2,3-dioxygenase (IDO) expression, resulting in depletion of tryptophan. We therefore assessed if lymphocytes could work as a shelter for the bacteria to escape IFN-γ. C. pneumoniae grew normally in human lymphoid Jurkat cells, even in the presence of IFN-γ or under stimulation with phorbol myristate acetate plus ionomycin. Although Jurkat cells expressed IFN-γ receptor CD119, their lack of IDO expression was confirmed by RT-PCR and western blotting. Also, C. pneumoniae survived in enriched human peripheral blood lymphocytes, even in the presence of IFN-γ. Furthermore, C. pneumoniae in spleen cells obtained from IFN-γ knockout mice with C57BL/6 background was maintained in a similar way to wild-type mice, supporting a minimal role of IFN-γ-related response for eliminating C. pneumoniae from lymphocytes. Thus, we concluded that IFN-γ did not remove C. pneumoniae from lymphocytes, possibly providing a shelter for C. pneumoniae to escape from the innate immune response, which has direct clinical significance. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2018-06-01

responses to vaccination. B lymphocytes play a significant role in the pathogenesis of rheumatoid arthritis, and B cell-depletion therapy has a major effect on the course of the disease. The advances in treatment of rheumatoid arthritis include the development of targeted therapies. Anti-TNF-α therapies are widely used despite potentially serious adverse events. The data on the effects of anti-TNF-α therapies on B lymphocytes are limited and conflicting. There is a need for larger studies to better understand the effects of newly discovered therapies on the different cells of the immune system. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2008-01-01

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

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

ClinicalTrials.gov

2017-10-23

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

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

PubMed Central

Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

2017-01-01

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

Evaluation of three high abundance protein depletion kits for umbilical cord serum proteomics

PubMed Central

2011-01-01

Background High abundance protein depletion is a major challenge in the study of serum/plasma proteomics. Prior to this study, most commercially available kits for depletion of highly abundant proteins had only been tested and evaluated in adult serum/plasma, while the depletion efficiency on umbilical cord serum/plasma had not been clarified. Structural differences between some adult and fetal proteins (such as albumin) make it likely that depletion approaches for adult and umbilical cord serum/plasma will be variable. Therefore, the primary purposes of the present study are to investigate the efficiencies of several commonly-used commercial kits during high abundance protein depletion from umbilical cord serum and to determine which kit yields the most effective and reproducible results for further proteomics research on umbilical cord serum. Results The immunoaffinity based kits (PROTIA-Sigma and 5185-Agilent) displayed higher depletion efficiency than the immobilized dye based kit (PROTBA-Sigma) in umbilical cord serum samples. Both the PROTIA-Sigma and 5185-Agilent kit maintained high depletion efficiency when used three consecutive times. Depletion by the PROTIA-Sigma Kit improved 2DE gel quality by reducing smeared bands produced by the presence of high abundance proteins and increasing the intensity of other protein spots. During image analysis using the identical detection parameters, 411 ± 18 spots were detected in crude serum gels, while 757 ± 43 spots were detected in depleted serum gels. Eight spots unique to depleted serum gels were identified by MALDI- TOF/TOF MS, seven of which were low abundance proteins. Conclusions The immunoaffinity based kits exceeded the immobilized dye based kit in high abundance protein depletion of umbilical cord serum samples and dramatically improved 2DE gel quality for detection of trace biomarkers. PMID:21554704

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

PubMed

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

2017-06-01

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

Impact of Depleting Therapeutic Monoclonal Antibodies on the Host Adaptive Immunity: A Bonus or a Malus?

PubMed Central

Deligne, Claire; Milcent, Benoît; Josseaume, Nathalie; Teillaud, Jean-Luc; Sibéril, Sophie

2017-01-01

Clinical responses to anti-tumor monoclonal antibody (mAb) treatment have been regarded for many years only as a consequence of the ability of mAbs to destroy tumor cells by innate immune effector mechanisms. More recently, it has also been shown that anti-tumor antibodies can induce a long-lasting anti-tumor adaptive immunity, likely responsible for durable clinical responses, a phenomenon that has been termed the vaccinal effect of antibodies. However, some of these anti-tumor antibodies are directed against molecules expressed both by tumor cells and normal immune cells, in particular lymphocytes, and, hence, can also strongly affect the host adaptive immunity. In addition to a delayed recovery of target cells, lymphocyte depleting-mAb treatments can have dramatic consequences on the adaptive immune cell network, its rebound, and its functional capacities. Thus, in this review, we will not only discuss the mAb-induced vaccinal effect that has emerged from experimental preclinical studies and clinical trials but also the multifaceted impact of lymphocytes-depleting therapeutic antibodies on the host adaptive immunity. We will also discuss some of the molecular and cellular mechanisms of action whereby therapeutic mAbs induce a long-term protective anti-tumor effect and the relationship between the mAb-induced vaccinal effect and the immune response against self-antigens. PMID:28855903

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

PubMed

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

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

PubMed

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

2017-04-01

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

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

PubMed

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2013-10-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

PubMed Central

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2014-01-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

ClinicalTrials.gov

2016-06-27

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

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

PubMed

Zana, Marianna; Szécsényi, Anita; Czibula, Agnes; Bjelik, Annamária; Juhász, Anna; Rimanóczy, Agnes; Szabó, Krisztina; Vetró, Agnes; Szucs, Péter; Várkonyi, Agnes; Pákáski, Magdolna; Boda, Krisztina; Raskó, István; Janka, Zoltán; Kálmán, János

2006-06-30

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

[Lymphocytic Clonal Expansion in Adult Patients with Epstein-Barr Virus-Associated Lymphoproliferative Disease].

PubMed

Zhong, Feng-Luan; Zhang, Hong-Yu; Zhang, Qian; Feng, Jia; Zhang, Wen-Li; Xu, Lei; Xu, Hai-Chan; Wen, Juan-Juan; Meng, Qing-Xiang

2017-12-01

To explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease. Peripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot. FCM showed only 1 case with clonal TCRVβ in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot. Detecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes

PubMed Central

Dekimpe, Emily; Van Woensel, Matthias; Roobrouck, Valerie D.; Bullens, Dominique M.; Pinxteren, Jef; Verfaillie, Catherine M.; Van Gool, Stefaan W.

2016-01-01

MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8+ cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated. MultiStem was nonimmunogenic for alloreactive CTL induction and was—even after major histocompatibility complex class I upregulation—insensitive to alloantigen-specific CTL-mediated lysis. Furthermore, MultiStem reduced CTL proliferation and significantly decreased perforin expression during the T-cell activation phase. As a consequence, MultiStem dose-dependently impaired the induction of CTL function. These effects of MultiStem were mediated predominantly through contact-dependent mechanisms. Moreover, MultiStem cells considerably influenced the expression of T-cell activation markers CD25, CD69, and human leukocyte antigen-DR. The MultiStem-induced CD8−CD69+ T-cell population displayed a suppressive effect on the induction of CTL function during a subsequent mixed-lymphocyte culture. Finally, the killer activity of activated antigen-specific CTLs during their cytolytic effector phase was also diminished in the presence of MultiStem. This study confirms that these clinical-grade MAPCs are an immune-modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs. Significance Because multipotent adult progenitor cells (MAPCs) are among the noteworthy adult mesenchymal stem cell populations for

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes.

PubMed

Plessers, Jeroen; Dekimpe, Emily; Van Woensel, Matthias; Roobrouck, Valerie D; Bullens, Dominique M; Pinxteren, Jef; Verfaillie, Catherine M; Van Gool, Stefaan W

2016-12-01

: MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8 + cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated. MultiStem was nonimmunogenic for alloreactive CTL induction and was-even after major histocompatibility complex class I upregulation-insensitive to alloantigen-specific CTL-mediated lysis. Furthermore, MultiStem reduced CTL proliferation and significantly decreased perforin expression during the T-cell activation phase. As a consequence, MultiStem dose-dependently impaired the induction of CTL function. These effects of MultiStem were mediated predominantly through contact-dependent mechanisms. Moreover, MultiStem cells considerably influenced the expression of T-cell activation markers CD25, CD69, and human leukocyte antigen-DR. The MultiStem-induced CD8 - CD69 + T-cell population displayed a suppressive effect on the induction of CTL function during a subsequent mixed-lymphocyte culture. Finally, the killer activity of activated antigen-specific CTLs during their cytolytic effector phase was also diminished in the presence of MultiStem. This study confirms that these clinical-grade MAPCs are an immune-modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs. Because multipotent adult progenitor cells (MAPCs) are among the noteworthy adult mesenchymal stem cell populations for immune therapy

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

PubMed

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

2015-04-01

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

Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

PubMed Central

Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

2015-01-01

We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

PubMed

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

2015-05-01

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2015-01-01

Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7–1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2–2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes. PMID:26491309

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

PubMed

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

2015-01-01

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

Both cladribine and alemtuzumab may effect MS via B-cell depletion.

PubMed

Baker, David; Herrod, Samuel S; Alvarez-Gonzalez, Cesar; Zalewski, Lukasz; Albor, Christo; Schmierer, Klaus

2017-07-01

To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests. Data were extracted and statistically analyzed. Either dose of cladribine (3.5 mg/kg; 5.25 mg/kg) tested in CLARITY reduced the annualized relapse rate to 0.16-0.18 over 96 weeks, and both doses were similarly effective in reducing the risk of MRI lesions and disability. Surprisingly, however, T-cell depletion was rather modest. Cladribine 3.5 mg/kg depleted CD4 + cells by 40%-45% and CD8 + cells by 15%-30%, whereas alemtuzumab suppressed CD4 + cells by 70%-95% and CD8 + cells by 47%-55%. However, either dose of cladribine induced 70%-90% CD19 + B-cell depletion, similar to alemtuzumab (90%). CD19 + cells slowly repopulated to 15%-25% of baseline before cladribine redosing. However, alemtuzumab induced hyperrepopulation of CD19 + B cells 6-12 months after infusion, which probably forms the substrate for B-cell autoimmunities associated with alemtuzumab. Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4 + T-cell depletion studies. The therapeutic drug-response relationship with cladribine is more consistent with lasting B-cell depletion and, coupled with the success seen with monoclonal CD20 + depletion, suggests that B-cell suppression could be the major direct mechanism of action.

Low Nourishment of Vitamin C Induces Glutathione Depletion and Oxidative Stress in Healthy Young Adults.

PubMed

Waly, Mostafa I; Al-Attabi, Zahir; Guizani, Nejib

2015-09-01

The present study was conducted to assess the status of vitamin C among healthy young adults in relation to serum antioxidant parameters [glutathione (GSH), thiols, and total antioxidant capacity, (TAC)], and oxidative stress markers [malondialdehyde (MDA), and nitrites plus nitrates (NN)]. A prospective study included 200 young adults, and their dietary intake was assessed by using food diaries. Fasting plasma vitamin C, serum levels of GSH, thiols, TAC, MDA, and NN were measured using biochemical assays. It was observed that 38% of the enrolled subjects, n=76, had an adequate dietary intake of vitamin C (ADI group). Meanwhile, 62%, n=124, had a low dietary intake of vitamin C (LDI group) as compared to the recommended dietary allowances. The fasting plasma level of vitamin C was significantly higher in the ADI group as compared to the LDI group. Oxidative stress in the sera of the LDI group was evidenced by depletion of GSH, low thiols levels, impairment of TAC, an elevation of MDA, and increased NN. In the ADI group, positive correlations were found between plasma vitamin C and serum antioxidant parameters (GSH, thiols, and TAC). Meanwhile, the plasma vitamin C was negatively correlated with serum MDA and NN levels. This study reveals a significant increase of oxidative stress status and reduced antioxidant capacity in sera from healthy young adults with low intake of the dietary antioxidant, vitamin C.

Time-on-task effects in children with and without ADHD: depletion of executive resources or depletion of motivation?

PubMed

Dekkers, Tycho J; Agelink van Rentergem, Joost A; Koole, Alette; van den Wildenberg, Wery P M; Popma, Arne; Bexkens, Anika; Stoffelsen, Reino; Diekmann, Anouk; Huizenga, Hilde M

2017-12-01

Children with attention-deficit/hyperactivity disorder (ADHD) are characterized by deficits in their executive functioning and motivation. In addition, these children are characterized by a decline in performance as time-on-task increases (i.e., time-on-task effects). However, it is unknown whether these time-on-task effects should be attributed to deficits in executive functioning or to deficits in motivation. Some studies in typically developing (TD) adults indicated that time-on-task effects should be interpreted as depletion of executive resources, but other studies suggested that they represent depletion of motivation. We, therefore, investigated, in children with and without ADHD, whether there were time-on-task effects on executive functions, such as inhibition and (in)attention, and whether these were best explained by depletion of executive resources or depletion of motivation. The stop-signal task (SST), which generates both indices of inhibition (stop-signal reaction time) and attention (reaction time variability and errors), was administered in 96 children (42 ADHD, 54 TD controls; aged 9-13). To differentiate between depletion of resources and depletion of motivation, the SST was administered twice. Half of the participants was reinforced during second task performance, potentially counteracting depletion of motivation. Multilevel analyses indicated that children with ADHD were more affected by time-on-task than controls on two measures of inattention, but not on inhibition. In the ADHD group, reinforcement only improved performance on one index of attention (i.e., reaction time variability). The current findings suggest that time-on-task effects in children with ADHD occur specifically in the attentional domain, and seem to originate in both depletion of executive resources and depletion of motivation. Clinical implications for diagnostics, psycho-education, and intervention are discussed.

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

ClinicalTrials.gov

2017-10-24

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

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

PubMed

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

2011-12-01

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

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

ClinicalTrials.gov

2013-07-01

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

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing.

PubMed

Luo, Ling; Wang, Huanling; Fan, Hongwei; Xie, Jing; Qiu, Zhifeng; Li, Taisheng

2018-03-01

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20-81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing

PubMed Central

Luo, Ling; Wang, Huanling; Fan, Hongwei; Xie, Jing; Qiu, Zhifeng; Li, Taisheng

2018-01-01

Abstract Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases. The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients. We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected. There were 28 adult onset CAEBV patients. The median age was 45 (range, 20–81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever. Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell. PMID:29489682

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

PubMed Central

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; Gregersen, Peter K.; Rai, Kanti R.

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, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity. PMID:21385850

Elevated expression of pleiotrophin in lymphocytic leukemia CD19+ B cells.

PubMed

Du, Chun-Xian; Wang, Lan; Li, Yan; Xiao, Wei; Guo, Qin-Lian; Chen, Fei; Tan, Xin-Ti

2014-10-01

Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Comparison between flowcytometry and immunoperoxidase staining for the enumeration of lymphocyte subsets.

PubMed

Dhaliwal, J S; Malar, B; Quck, C K; Sukumaran, K D; Hassan, K

1991-06-01

Immunoperoxidase staining was compared with flowcytometry for the enumeration of lymphocyte subsets. The percentages obtained for peripheral blood lymphocytes using immunoperoxidase (CD3 = 76 CD4 = 27.9, B = 10.7 CD4/CD8 = 1.8) differed significantly from those obtained by flowcytometry (CD3 = 65.7 CD4 = 39.4, CD8 = 25.6, B = 16.7, HLA DR = 11.9 CD4/CD8 = 1.54) for certain subsets (CD3, CD4, B). There was no significant difference in lymphocyte subsets between children and adults using the same method. These differences are probably due to the different methods used to prepare lymphocytes for analysis. Other factors that should also be considered are the presence of CD4 antigen on monocytes and CD8 on natural killer cells.

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

PubMed

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

1994-01-01

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

Executive function depletion in children and its impact on theory of mind.

PubMed

Powell, Lindsey J; Carey, Susan

2017-07-01

The current studies provide an experimental, rather than correlational, method for testing hypotheses about the role of executive function (EF) in conceptual development. Previous research has established that adults' tendency to deploy EF can be temporarily diminished by use. Exercising self-control in one context decreases adults' performance on other EF demanding tasks immediately thereafter. Using two different depletion methods, Experiments 1 and 3 extend this finding to preschool-aged children. Experiments 2 and 4 make use of these EF depletion methods to elucidate the role of EF in children's theory of mind reasoning. Experiment 2 shows that EF depletion affects 5-year-olds' ability to predict another's behavior on the basis of that person's false belief, and Experiment 4 shows that this negative effect of depletion extends to 4- and 5-year-olds' ability to explain others' behavior on the basis of their false beliefs. These findings provide direct evidence that EF is required for the expression of an understanding of others' false beliefs across a variety of task demands, even in children who clearly have the capacity to construct such representations. We suggest ways in which depletion may be used as a tool for further investigating the role of executive function in cognitive development. Copyright © 2017. Published by Elsevier B.V.

Suppression of the formation of polyamines and macromolecules by dl-α-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) in phytohaemagglutinin-activated human lymphocytes

PubMed Central

Jänne, Juhani; Hovi, Tapani; Hölttä, Erkki

1979-01-01

1. The activation of human peripheral blood lymphocytes by phytohaemagglutinin in vitro was accompanied by striking increases in the concentrations of the natural polyamines putrescine, spermidine and spermine. 2. The enhanced accumulation of polyamines could be almost totally abolished by dl-α-difluoromethylornithine, a newly discovered irreversible inhibitor of l-ornithine decarboxylase (EC 4.1.1.17), or by methylglyoxal bis(guanylhydrazone) {1,1′-[(methylethanediylidene)dinitrilo]diguanidine}, an inhibitor of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50). The inhibition of polyamine accumulation was associated with a marked suppression of DNA synthesis, which was partially or totally reversed by low concentrations of exogenous putrescine, spermidine, spermine and cadaverine and by higher concentrations of 1,3-diaminopropane. 3. In contrast with some earlier studies, we found that methylglyoxal bis(guanylhydrazone), at concentrations that were sufficient to prevent polyamine accumulation, also caused a clear inhibition of protein synthesis in the activated lymphocytes. Similar results were obtained with difluoromethylornithine. The decrease in protein synthesis caused by both compounds preceded the impairment of DNA synthesis. The inhibition of protein synthesis by difluoromethylornithine was fully reversed by exogenous putrescine, spermidine and spermine, and that caused by methylglyoxal bis(guanylhydrazone) by spermidine and spermine. In further support of the idea that the inhibition of protein synthesis by these compounds was related to the polyamine depletion, we found that difluoromethylornithine caused a dose-dependent decrease in the incorporation of [14C]leucine into lymphocyte proteins which closely correlated with the decreased concentrations of cellular spermidine. 4. Difluoromethylornithine and methylglyoxal bis(guanylhydrazone) also elicited a variable depression in the incorporation of [3H]uridine and [14C]adenine into total RNA. The

Suppression of the formation of polyamines and macromolecules by DL-alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) in phytohaemagglutinin-activated human lymphocytes.

PubMed

Hölttä, E; Jänne, J; Hovi, T

1979-01-15

1. The activation of human peripheral blood lymphocytes by phytohaemagglutinin in vitro was accompanied by striking increases in the concentrations of the natural polyamines putrescine, spermidine and spermine. 2. The enhanced accumulation of polyamines could be almost totally abolished by dl-alpha-difluoromethylornithine, a newly discovered irreversible inhibitor of l-ornithine decarboxylase (EC 4.1.1.17), or by methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidene)dinitrilo]diguanidine}, an inhibitor of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50). The inhibition of polyamine accumulation was associated with a marked suppression of DNA synthesis, which was partially or totally reversed by low concentrations of exogenous putrescine, spermidine, spermine and cadaverine and by higher concentrations of 1,3-diaminopropane. 3. In contrast with some earlier studies, we found that methylglyoxal bis(guanylhydrazone), at concentrations that were sufficient to prevent polyamine accumulation, also caused a clear inhibition of protein synthesis in the activated lymphocytes. Similar results were obtained with difluoromethylornithine. The decrease in protein synthesis caused by both compounds preceded the impairment of DNA synthesis. The inhibition of protein synthesis by difluoromethylornithine was fully reversed by exogenous putrescine, spermidine and spermine, and that caused by methylglyoxal bis(guanylhydrazone) by spermidine and spermine. In further support of the idea that the inhibition of protein synthesis by these compounds was related to the polyamine depletion, we found that difluoromethylornithine caused a dose-dependent decrease in the incorporation of [(14)C]leucine into lymphocyte proteins which closely correlated with the decreased concentrations of cellular spermidine. 4. Difluoromethylornithine and methylglyoxal bis(guanylhydrazone) also elicited a variable depression in the incorporation of [(3)H]uridine and [(14)C]adenine into total RNA

Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation.

PubMed

Kanazawa, Hiroyuki; Fukuda, Akinari; Mali, Vidyadhar Padmakar; Rahayatri, Tri Hening; Hirata, Yoshihiro; Sasaki, Kengo; Uchida, Hajime; Shigeta, Takanobu; Sakamoto, Seisuke; Matsumoto, Kimikazu; Kasahara, Mureo

2016-05-01

LT from ABO-I donors requires preconditioning regimens to prevent postoperative catastrophic AMR. NAC for HBL is known to cause myelosuppression leading to a reduction in the number and function of lymphocytes. We investigated this chemotherapy-induced myelosuppression in HBL patients listed for LT from ABO-I donors with reference to the kinetics of B, T cells, and anti-ABO blood type isoagglutinin titers. Between 2005 and 2015, of the 319 patients who underwent LDLT at our institute, 12 were indicated for unresectable HBL. Three patients with unresectable HBL who underwent LDLT from ABO-I donors are included in this study. Immunosuppression consisted of a standard regime of tacrolimus and low-dose steroids as in ABO compatible/identical LDLT. No additional preoperative therapies for B-cell depletion were used. Absolute lymphocyte counts, lymphocyte subsets (including CD20+ B cells, CD3+CD4+ T cells and CD3+CD8+ T cells), and anti-ABO blood type isoagglutinin titers were measured before LDLT and postoperatively. The median age at diagnosis was 19 months (range, 3-31 months). The median follow-up was seven months (range, 6-15 months). The median interval from the last NAC to LDLT was 33 days (range, 25-52 days). The median interval from LDLT to adjuvant chemotherapy was 28 days (range, 22-36 days). The counts of CD20+ B cells before LDLT were depleted to median 5 cells/mm(3) (range, 0-6 cells/mm(3)). There was a transient rebound in the CD20+ B cell counts on day seven (maximum of 82 cells/mm(3)) followed by a decline starting at 14 days after LDLT that was sustained for the duration of adjuvant chemotherapy. Anti-ABO blood type isoagglutinin titers were lowered to between 1:1 and 1:16 before LDLT and remained low for the duration of follow-up in this study. All of the three patients remained in good health without either acute cellular or AMR after LDLT. The B-cell depletion that occurs after cisplatin-based chemotherapy for HBL may help accomplish safe ABO-I LDLT

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

ClinicalTrials.gov

2014-10-30

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

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

ClinicalTrials.gov

2017-12-26

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

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

PubMed Central

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

2015-01-01

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

ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.

PubMed

Bassoy, Esen Yonca; Kasahara, Atsuko; Chiusolo, Valentina; Jacquemin, Guillaume; Boydell, Emma; Zamorano, Sebastian; Riccadonna, Cristina; Pellegatta, Serena; Hulo, Nicolas; Dutoit, Valérie; Derouazi, Madiha; Dietrich, Pierre Yves; Walker, Paul R; Martinvalet, Denis

2017-06-01

Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. © 2017 The Authors.

Age moderates the effect of acute dopamine depletion on passive avoidance learning.

PubMed

Kelm, Mary Katherine; Boettiger, Charlotte Ann

2015-04-01

Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task. We tested 16 (5 female) adults (ages 22-40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[-]), would affect PAL task performance. We found that P/T[-] beverage effects on PAL performance were modulated by age. Specifically, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, -0.71 - -2.27, r=-0.74, p=0.001). Moreover, P/T depletion improved learning from punishment in adults (ages 26-40) while it impaired learning from punishment in emerging adults (ages 22-25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[-] beverage also made more errors on the P/T[-] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[-] beverage negatively correlated with learning from reward on the P/T[-] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary with age. Copyright © 2015 Elsevier Inc. All rights

Age Moderates the Effect of Acute Dopamine Depletion on Passive Avoidance Learning

PubMed Central

Kelm, Mary Katherine; Boettiger, Charlotte Ann

2015-01-01

Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task We tested 16 (5 female) adults (ages 22–40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[−]), would affect performance on the PAL task. We found that P/T[−] beverage effects on PAL performance were modulated by age. In particular, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, −0.71 – −2.27, r=−0.74, p=0.001). Moreover, in this small sample, P/T depletion improved learning from punishment in adults (ages 26–40) while it impaired learning from punishment in emerging adults (ages 22–25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[−] beverage also made more errors on the P/T[−] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[−] beverage negatively correlated with learning from reward on the P/T[−] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary

Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance

PubMed Central

Robertson, Charles M.; Perrone, Erin E; McConnell, Kevin W.; Dunne, W. Michael; Boody, Barrett; Brahmbhatt, Tejal; Diacovo, M. Julia; Van Rooijen, Nico; Hogue, Lisa A.; Cannon, Carolyn L.; Buchman, Timothy G.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2008-01-01

Background Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare. Materials and Methods We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and resistant as well as Panton-Valentine leukocidin positive and negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, Balb/c, ND4, n=148). The immunologic basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4 or 7 days prior to the onset of pneumonia. Results Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% vs. 90% alive at 7 days, p<0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 hours but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary MCP-1 (822 pg/ml vs. 150 pg/ml, p<0.05). In contrast, pulmonary histologic appearance was similar in both groups as was dry/wet lung weight. Conclusions These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response. PMID:18621398

Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance.

PubMed

Robertson, Charles M; Perrone, Erin E; McConnell, Kevin W; Dunne, W Michael; Boody, Barrett; Brahmbhatt, Tejal; Diacovo, M Julia; Van Rooijen, Nico; Hogue, Lisa A; Cannon, Carolyn L; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

2008-12-01

Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare. We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia. Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight. These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.

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

ClinicalTrials.gov

2013-07-15

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

Human podocyte depletion in association with older age and hypertension.

PubMed

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

2016-04-01

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

Lymphocyte thymidine kinase and treatment response in acute lymphocytic leukemia.

PubMed

Russo, S A; Harris, M B; Greengard, O

1987-01-01

The activity of thymidine kinase (TK) and the proportion of its isozymes (TK1/TK2) were studied in peripheral lymphoid cells of 37 children with acute lymphocytic leukemia (ALL). The high TK in 25 untreated subjects (31.5 +/- 8.9) decreased during chemotherapy-induced remission to uniformly low (5.3 +/- 0.4) normal values, and rose again during relapse to a mean of (24.8 +/- 8.1). The proportion of isozyme 1 followed the same pattern but TK was a more sensitive indicator of disease state. The lymphocyte fractions' TK (per mg protein) correlated with the number (per ml blood) of WBCs, blasts and lymphocytes. Although the higher TK of blasts than of apparently normal lymphocytes was confirmed in cases permitting clean physical separation, the lymphocyte fraction of several untreated subjects with minimal blast counts also exhibited elevated TK. Moreover, this elevation was also seen in relapsed cases even if their blood (unlike bone marrow) was devoid of blasts. The results indicate that quantification of TK can reveal a subpopulation of maldifferentiated lymphocytes which are microscopically normal and that it may provide an objective parameter of prognostic differences between ALL subjects with similar hematological characteristics.

Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE distribution patterns in peripheral blood lymphocytes of Spanish adult smokers compared to non-smokers.

PubMed

Sebastià, Natividad; Hervás, David; Almonacid, Miguel; Villaescusa, Juan Ignacio; Soriano, José Miguel; Sahuquillo, Vicenta; Esteban, Valentín; Barquinero, Joan Francesc; Verdú, Gumersindo; Cervera, José; Such, Esperanza; Montoro, Alegría

2014-04-01

According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n=48) and non-smokers (n=53), aged from 18 to 49 years, was studied using SCE levels in peripheral lymphocytes. Heavy smoking (≥ 10 cigarettes per day) increased significantly the SCE frequency and the HFC parameters. Neither age nor sex significantly influenced the frequencies in the groups studied. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth.

PubMed

Zhao, Bo; Zou, James; Wang, Hongfang; Johannsen, Eric; Peng, Chih-wen; Quackenbush, John; Mar, Jessica C; Morton, Cynthia Casson; Freedman, Matthew L; Blacklow, Stephen C; Aster, Jon C; Bernstein, Bradley E; Kieff, Elliott

2011-09-06

Epstein-Barr virus nuclear antigen 2 (EBNA2) regulation of transcription through the cell transcription factor RBPJ is essential for resting B-lymphocyte (RBL) conversion to immortal lymphoblast cell lines (LCLs). ChIP-seq of EBNA2 and RBPJ sites in LCL DNA found EBNA2 at 5,151 and RBPJ at 10,529 sites. EBNA2 sites were enriched for RBPJ (78%), early B-cell factor (EBF, 39%), RUNX (43%), ETS (39%), NFκB (22%), and PU.1 (22%) motifs. These motif associations were confirmed by LCL RBPJ ChIP-seq finding 72% RBPJ occupancy and Encyclopedia Of DNA Elements LCL ChIP-seq finding EBF, NFκB RELA, and PU.1 at 54%, 31%, and 17% of EBNA2 sites. EBNA2 and RBPJ were predominantly at intergene and intron sites and only 14% at promoter sites. K-means clustering of EBNA2 site transcription factors identified RELA-ETS, EBF-RUNX, EBF, ETS, RBPJ, and repressive RUNX clusters, which ranked from highest to lowest in H3K4me1 signals and nucleosome depletion, indicative of active chromatin. Surprisingly, although quantitatively less, the same genome sites in RBLs exhibited similar high-level H3K4me1 signals and nucleosome depletion. The EBV genome also had an LMP1 promoter EBF site, which proved critical for EBNA2 activation. LCL HiC data mapped intergenic EBNA2 sites to EBNA2 up-regulated genes. FISH and chromatin conformation capture linked EBNA2/RBPJ enhancers 428 kb 5' of MYC to MYC. These data indicate that EBNA2 evolved to target RBL H3K4me1 modified, nucleosome-depleted, nonpromoter sites to drive B-lymphocyte proliferation in primary human infection. The primed RBL program likely supports antigen-induced proliferation.

Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds.

PubMed Central

Lipsky, P E; Ziff, M

1977-01-01

Gold sodium thiomalate (GST) inhibited in vitro antigen- and mitogen-triggered human lymphocyte DNA synthesis. Inhibition of responsiveness was observed with concentrations of GST equivalent to gold levels found in serum or tissues of patients receiving chrysotherapy, Inhibition was dependent upon the gold ion itself since GST and gold chloride were both inhibitory whereas thiomalic acid was not. Inhibition could not be explained by nonspecific killing of cells or by an alteration in the kinetics of the responses. GST inhibited mitogen-induced proliferation most effectively when present from the initiation of culture and could not inhibit the responsiveness of cells which previously had been activated by concanvalin A. These findings indicated that GST blocked a critical early step in lymphocyte activation. The degree of GST-induced inhibition of proliferation was increased in cultures of cells partially depleted of monocytes. Moreover, inhibition was reversed by supplementation of these cultures with purified monocytes. These observations suggested that GST blocked thymus-derived (T)-lymphocyte activation by interfering with a requisite function of the monocyte population in initiating such responses. Prolonged incubation of peripheral blood mononuclear cells with GST resulted in diminished mitogen responsiveness upon subsequent culture in the absence of gold. The addition of fresh monocytes restored responsiveness to these populations. Furthermore, preincubation of purified monocytes with GST rendered them deficient in their ability to support mitogen-induced T-lymphocyte proliferation on subsequent culture. These observations indicate that the major effect of GST results from interference with the functional capability of the monocyte population. PMID:838859

Lymphocyte-dependent antibodies in uveitis.

PubMed

Pápai, I; Lehrner, J

1976-01-01

Lymphocyte-dependent antibodies were revealed in the serum of patients suffering from uveitis of various aetiologies. The serum was incubated with normal uveal tissue and the binding of non-immune human lymphocytes was investigated. In three cases of sympathetic ophthalmitis the lymphocytes accumulated around the melanine granules, while in another 17 patients with uveitis cases the lymphocytes accumulated around the capillaries. Uveal tissue incubated with control sera failed to bound lymphocytes. The lymphocytic infiltration in certain cases of chronic uveitis suggested the role of lymphocyte-mediating antibodies in the aetiology of these cases.

Lymphocyte Functions in Microgravity

NASA Technical Reports Server (NTRS)

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

1999-01-01

To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

[Acquirement of autologous murine cytotoxic T lymphocytes via cryopreservation of lymphocytes].

PubMed

Wang, Lei; Peng, Na; Hu, Xiaoyan; Liang, Wentao; Liang, Kai; Peng, Guizhu

2016-11-01

Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10 6 /mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs). Dendritic cells (DCs) were co-cultured with fresh allogenic lymphocytes and post-cryopreservation autologous lymphocytes to obtain CTLs. The viable cells were counted by trypan blue staining; the percentages of CD3 + T cells and regulatory T cells (Tregs) were determined by flow cytometry; the levels of supernatant IFN-γ were detected through ELISA and the cytotoxicity was evaluated by lactate dehydrogenase (LDH) assay. Results The rate of viable lymphocytes declined to 78% after cryopreservation, and there were no significant differences in the percentages of CD3 + T cells and Tregs between pre-cryopreservation and post-cryopreservation. There were no significant differences in the proliferation of Tregs, the level of IFN-γ and the cytotoxicity between the fresh CIKs and cryopreservation CIKs, and the similar results were get between the autologous CTLs and allogenic CTLs. Conclusion The autologous CTLs acquired via cryopreservation of lymphocytes is equivalent to the allogenic CTLs with the similar proliferation and killing activity in vitro.

A comparative study on efficiency of adult fibroblast, putative embryonic stem cell and lymphocyte as donor cells for production of handmade cloned embryos in goat and characterization of putative ntES cells obtained from these embryos.

PubMed

Dutta, Rahul; Malakar, Dhruba; Khate, Keviletsu; Sahu, Shailendra; Akshey, Yogesh; Mukesh, Manishi

2011-09-15

The main purpose of the experiment was to compare the efficiency of three cell types, namely adult fibroblast, putative embryonic stem (ES) cell, and lymphocyte, as donor cells for somatic cell nuclear transfer by handmade cloning in goats. The outcome clearly shows that putative embryonic stem cells, with a cleavage and blastocyst production rate of 74.69% ± 3.92 and 39.75% ± 3.86, respectively, performs better in comparison to adult fibroblast cell and lymphocyte. Between adult fibroblast cell and lymphocyte no statistically significant difference exists at P < 0.05. An overall cleavage and blastocyst formation rate of 67.41% ± 3.92 and 26.96% ± 3.86 was obtained using adult fibroblast donor cells. The study establishes beyond doubt the reprogrammability of lymphocyte by handmade cloning (HMC) protocol with a cleavage and blastocyst production rate of 56.47% ± 3.92 and 24.70% ± 3.86, respectively. PCR analysis of highly polymorphic 286 bp fragment of MHC II DRB genes of cloned embryos and three donor cells were performed to verify the cloned embryos. The amplified PCR products were subjected to SSCP to confirm their genetic identity. The karyotyping of the cloned embryos showed normal chromosomal status as expected in goat. Significantly, in the second stage of the experiment, the produced cloned embryos were successfully used to derive ntES-like cells. The rate of primary colony formation rate was 62.50% ± 4.62 for fibroblast donor cell derived embryos. The same was 60.60% ± 4.62 for putative ES donor cell derived embryos and 66.66% ± 4.62 for lymphocyte donor cell derived embryos, respectively. The putative ntES colonies were positively characterized for alkaline phosphatase, Oct-4, TRA-1-60, TRA-1-81, Sox-2, and Nanog by Immunocytochemistry and Reverse Transcription PCR. To further validate the stem ness, the produced putative ntES colonies were differentiated to embryoid bodies. Immunocytochemistry revealed that embryoid bodies expressed NESTIN

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

ClinicalTrials.gov

2015-11-10

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

Health investigations of depleted-uranium clean-up workers.

PubMed

Milacic, Snezana

2008-01-01

The soil contaminated by depleted uranium (238U) ammunition during the NATO bombing of Serbia and Montenegro was cleaned-up for four months in 2002. A team of 11 clean-up workers (expert members) were medically examined three times: before decontamination as a preliminary medical check-up, immediately after decontamination, and four years after cleaning up contaminated ground. This short report presents investigations and health risk assessments of clean-up workers in radioactive decontamination operations and an assessment of the environmental health perspectives for citizens living in surrounding areas. The method of initial health disorders was used, analyzing the most sensitive biological materials, such as blood cells or chromosome damage, DNA strand breaks, radio-toxicological examination of urine. The total number of blood cells did not change, but variations of the relative number (percentage) of cells in the leukocyte formula were observed. The total number of DNA alterations was higher immediately after decontamination than before decontamination. Four years after decontamination the number of DNA alterations had decreased. However, the number of damaged cells (lymphocytes containing chromosome lesions) was higher in both medical examinations, immediately after and four years after decontamination. Disease or tumours due to 238U did not develop in the group of depleted uranium clean-up workers during the investigation period of four years. Further monitoring of haematological and chromosomal effects and the health condition of workers is necessary.

OXIDATIVE STRESS AND TREG DEPLETION IN LUPUS PATIENTS WITH ANTI-PHOSPHOLIPID SYNDROME

PubMed Central

Lai, Zhi-wei; Marchena-Mendez, Ivan; Perl, Andras

2015-01-01

Anti-phospholipid antibodies (APLA) represent a diagnostic criterion of systemic lupus erythematosus (SLE) and cause morbidity, termed anti-phospholipid syndrome (APS). Activation of the mechanistic target of rapamycin (mTOR) has been recently associated with APS. mTOR is a sensor of oxidative stress. Therefore, we examined mitochondrial mass, superoxide production, mTOR and FoxP3 expression in 72 SLE patients, twelve of whom also had APS, and 54 healthy controls by flow cytometry. Mitochondrial mass was increased in CD4−CD8− double-negative (DN) T cells of SLE patients with APS (2.7-fold) in comparison to those without APS (1.7-fold; p=0.014). Superoxide production was increased in all lymphocyte subsets of APS patients. FoxP3+ cells were depleted within CD4+CD25+ Tregs in patients with APS (28.4%) relative to those without APS (46.3%, p=0.008). mTOR activity was similar between SLE patients with and without APS. Thus, oxidative stress and Treg depletion rather than mTOR activation underlie APS in patients with SLE. PMID:25862984

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

PubMed

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

2005-02-10

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

T lymphocyte subpopulations diverge in commercially raised chickens

PubMed Central

Bridle, Byram W.; Julian, Richard; Shewen, Patricia E.; Vaillancourt, Jean-Pierre

2006-01-01

Abstract To evaluate immunocompetence in commercially raised chickens, we immunophenotyped Dekalb Delta and H&N White Leghorn (WLH) hybrids, 20 chickens in each of 3 age groups (9 wk [juvenile], 25 wk [young adult], and 79 or 80 wk [adult]), for circulating CD3+, CD4+, CD8+, TCR1+, TCR2+, and TCR3+ lymphocytes. The proportion of CD3+ T cells, including CD4+ and CD8+ subsets, was increased in the hybrids as compared with published values for laboratory-raised outbred WLH chickens. The proportion of the TCR2+ (Vβ1) T cell subpopulation was also increased. An age-related decrease in the proportion of TCR1+ (γδ) T cells was noted in both hybrids. Further, a remarkably low CD4:CD8 ratio was evident in all age groups of both hybrids, indicating decreased immunocompetence. Overall, these experiments provide age-related proportions of various peripheral-blood T lymphocyte subpopulations in commercially raised Dekalb Delta and H&N chickens that diverge from the proportions in laboratory-raised outbred WLH chickens and suggest reduced immunocompetence. Such a decline in immunocompetence, including humoral immune capacity, could be attributed to genetic selection for production traits, environmental factors associated with commercial operations, and intense immunization. PMID:16850940

Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiley, J.S.; Dubyak, G.R.

Extracellular adenosine triphosphate (ATP) is known to reversibly increase the cation permeability of a variety of freshly isolated and cultured cell types. In this study the effects of extracellular ATP were studied using peripheral blood lymphocytes (PBL) isolated from both normal subjects and from patients with chronic lymphocytic leukemia (CLL). Changes in the permeability to Na+, Rb+, and Li+ ions were measured using conventional isotope and flame photometry techniques. In addition, changes in cytosolic (Ca2+) were fluorimetrically monitored to assess possible changes in net Ca2+ influx. ATP produced a 12-fold increase in 22Na+ influx into CLL cells but only amore » 3.5-fold increase in this flux in PBL cells. A maximal response was produced by 0.1 mmol/L ATP in the absence of Mg2+, while a twofold molar excess of Mg2+ over ATP abolished the response. ATP had no effect on the passive (ouabain-insensitive) 86Rb+ influx into PBL cells but stimulated this flux by fivefold in the CLL cells. Li+ influx into CLL cells was also stimulated threefold by ATP. Under these same conditions ATP also produced a net increase in total cell Na and a decrease in total cell K in the CLL cells. Exclusion of two normally impermeable dyes, trypan blue and ethidium bromide, was not altered in the ATP-treated CLL cells. Finally, extracellular ATP (3 mmol/L) produced no significant change in the cytosolic (Ca2+) of normal, monocyte-depleted populations of PBL. Conversely, this same concentration of ATP produced a very rapid and a significant (an average threefold peak change) increase in the cytosolic (Ca2+) of cell preparations derived from five out of nine CLL patients. In these latter CLL cells, the ATP-induced elevation in cytosolic (Ca2+) appeared to be due to a net increase in Ca2+ influx, since no elevations were observed when the extracellular (Ca2+) was reduced to less than 0.1 mmol/L.« less

Tumor infiltrating lymphocytes in ovarian cancer

PubMed Central

Santoiemma, Phillip P; Powell, Daniel J

2015-01-01

The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. PMID:25894333

Adult advanced chronic lymphocytic leukemia: computational analysis of whole-body CT documents a bone structure alteration.

PubMed

Fiz, Francesco; Marini, Cecilia; Piva, Roberta; Miglino, Maurizio; Massollo, Michela; Bongioanni, Francesca; Morbelli, Silvia; Bottoni, Gianluca; Campi, Cristina; Bacigalupo, Andrea; Bruzzi, Paolo; Frassoni, Francesco; Piana, Michele; Sambuceti, Gianmario

2014-06-01

To assess the presence of alteration of bone structure and bone marrow metabolism in adult patients who were suspected of having advanced chronic lymphocytic leukemia (ACLL) by using a computational prognostic model that was based on computational analysis of positron emission tomography (PET)/computed tomography (CT) images. In this retrospective study, all patients signed written informed consent as a requisite to undergo PET/CT examination. However, due to its observational nature, approval from the ethical committee was not deemed necessary. Twenty-two previously untreated chronic lymphocytic leukemia patients underwent PET/CT for disease progression. PET/CT images were analyzed by using dedicated software, capable of recognizing an external 2-pixel bone ring whose Hounsfield coefficient served as cutoff to recognize trabecular and compact bone. PET/CT data from 22 age- and sex-matched control subjects were used as comparison. All data are reported as means ± standard deviations. The Student t test, log-rank, or Cox proportional hazards model were used as appropriate, considering a difference with a P value of less than .05 as significant. Trabecular bone was expanded in ACLL patients and occupied a larger fraction of the skeleton with respect to control subjects (mean, 39% ± 5 [standard deviation] vs 31% ± 7; ie, 32 of 81 mL/kg of ideal body weight vs 27 of 86 mL/kg of ideal body weight, respectively; P < .001). After stratification according to median value, patients with a ratio of trabecular to skeletal bone volume of more than 37.3% showed an actuarial 2-year survival of 18%, compared with 82% for those with a ratio of less than 37.3% (P < .001), independent from age, sex, biological markers, and disease duration. These data suggest that computational assessment of skeletal alterations might represent a new window for prediction of the clinical course of the disease.

Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-01-12

Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections.

PubMed

Grimaldi, David; Le Bourhis, Lionel; Sauneuf, Bertrand; Dechartres, Agnès; Rousseau, Christophe; Ouaaz, Fatah; Milder, Maud; Louis, Delphine; Chiche, Jean-Daniel; Mira, Jean-Paul; Lantz, Olivier; Pène, Frédéric

2014-02-01

In between innate and adaptive immunity, the recently identified innate-like mucosal-associated invariant T (MAIT) lymphocytes display specific reactivity to non-streptococcal bacteria. Whether they are involved in bacterial sepsis has not been investigated. We aimed to assess the number and the time course of circulating innate-like T lymphocytes (MAIT, NKT and γδ T cells) in critically ill septic and non-septic patients and to establish correlations with the further development of intensive care unit (ICU)-acquired infections. We prospectively enrolled consecutive patients with severe sepsis and septic shock. Controls were critically ill patients with non-septic shock and age-matched healthy subjects. Circulating innate-like lymphocytes were enumerated using a flow cytometry assay at day 1, 4 and 7. One hundred and fifty six patients (113 severe bacterial infections, 36 non-infected patients and 7 patients with severe viral infections) and 26 healthy subjects were enrolled into the study. Patients with severe bacterial infections displayed an early decrease in MAIT cell count [median 1.3/mm(3); interquartile range (0.4-3.2)] as compared to control healthy subjects [31.1/mm(3) (12.1-45.2)], but also to non-infected critically ill patients [4.3/mm(3) (1.4-13.2)] (P < 0.0001 for all comparisons). In contrast NKT and γδ T cell counts did not differ between patients groups. The multivariate analysis identified non-streptococcal bacterial infection as an independent determinant of decrease in MAIT cell count. Furthermore, the incidence of ICU-acquired infections was higher in patients with persistent MAIT cell depletion. This large human study provides valuable information about MAIT cells in severe bacterial infections. The persistent depletion of MAIT cells is associated with the further development of ICU-acquired infections.

Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

ClinicalTrials.gov

2018-04-20

Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes

PubMed Central

Gomes, J A P; Dua, H S; Rizzo, L V; Nishi, M; Joseph, A; Donoso, L A

2004-01-01

Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. PMID:14736792

The Chemokine CCL4 (MIP-1β) Evokes Antinociceptive Effects in Mice: a Role for CD4+ Lymphocytes and Met-Enkephalin.

PubMed

García-Domínguez, Mario; Lastra, Ana; Folgueras, Alicia R; Cernuda-Cernuda, Rafael; Fernández-García, María Teresa; Hidalgo, Agustín; Menéndez, Luis; Baamonde, Ana

2018-06-15

In the present study, we characterize the antinociceptive effects produced by the chemokine CCL4 in mice. The intraplantar administration of very low doses of CCL4 (0.1-3 pg) produced bilateral antinociception assessed by the unilateral hot-plate test (UHP) without evoking chemotactic responses at the injection site. Moreover, the subcutaneous administration of CCL4 (3-100 pg/kg) also yielded bilateral antinociception in the UHP and the paw pressure test and reduced the number of spinal neurons that express Fos protein in response to noxious stimulation. The implication of peripheral CCR5 but not CCR1 in CCL4-evoked antinociception was deduced from the inhibition produced by systemic but not intrathecal, administration of the CCR5 antagonist DAPTA, and the inefficacy of the CCR1 antagonist J113863. Besides, the inhibition observed after subcutaneous but not intrathecal administration of naloxone demonstrated the involvement of peripheral opioids and the efficacy of naltrindole but not cyprodime or nor-binaltorphimine supported the participation of δ-opioid receptors. In accordance, plasma levels of met-enkephalin, but not β-endorphin, were augmented in response to CCL4. Likewise, CCL4-evoked antinociception was blocked by the administration of an anti-met-enk antibody. Leukocyte depletion experiments performed with cyclophosphamide, anti-Ly6G, or anti-CD3 antibodies indicated that the antinociceptive effect evoked by CCL4 depends on circulating T lymphocytes. Double immunofluorescence experiments showed a four times more frequent expression of met-enk in CD4 + than in CD8 + T lymphocytes. CCL4-induced antinociception almost disappeared upon CD4 + , but not CD8 + , lymphocyte depletion with selective antibodies, thus supporting that the release of met-enk from CD4 + lymphocytes underlies the opioid antinociceptive response evoked by CCL4.

Effects of tryptophan depletion on the performance of an iterated Prisoner's Dilemma game in healthy adults.

PubMed

Wood, Richard M; Rilling, James K; Sanfey, Alan G; Bhagwagar, Zubin; Rogers, Robert D

2006-05-01

Adaptive social behavior often necessitates choosing to cooperate with others for long-term gains at the expense of noncooperative behaviors giving larger immediate gains. Although little is know about the neural substrates that support cooperative over noncooperative behaviors, recent research has shown that mutually cooperative behavior in the context of a mixed-motive game, the Prisoner's Dilemma (PD), is associated with increased neural activity within reinforcement circuitry. Other research attests to a role for serotonin in the modulation of social behavior and in reward processing. In this study, we used a within-subject, crossover, double-blind design to investigate performance of an iterated, sequential PD game for monetary reward by healthy human adult participants following ingestion of an amino-acid drink that either did (T+) or did not (T-) contain l-tryptophan. Tryptophan depletion produced significant reductions in the level of cooperation shown by participants when playing the game on the first, but not the second, study days. This effect was accompanied by a significantly diminished probability of cooperative responding given previous mutually cooperative behavior. These data suggest that serotonin plays a significant role in the acquisition of socially cooperative behavior in human adult participants, and suggest novel hypotheses concerning the serotonergic modulation of reward information in socially cooperative behavior in both health and psychiatric illness.

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

PubMed

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.

Hapten-specific T-Cell Unresponsiveness Induced by Benzylpenicilloyl Autologous Gamma Globulin Conjugates in Human Lymphocytes In Vitro

PubMed Central

Geha, Raif S.; Fruchter, Lazar; Borel, Yves

1980-01-01

The aim of these studies was to determine whether unresponsiveness to the main determinant of penicillin, benzylpenicilloyl, can be induced in human peripheral lymphocytes in vitro by conjugates of benzylpenicilloyl (BPO) autologous gamma globulin (HGG). Initially it was shown that conjugates of BPO-keyhole limpet hemocyanin (KLH) elicited lymphocyte proliferation in the peripheral blood lymphocytes of six out of nine adult individuals in vitro. In contrast, conjugates of dinitrophenylated KLH and of BPO-HGG and the carriers HGG and KLH alone failed to do so. Similarly, release of the non-specific helper factor, lymphocyte mitogenic factor (LMF) occurred only after BPO-KLH stimulation. LMF activity was measured by B-cell proliferation and incorporation of radioactive amino acids into secreted immunoglobulin. Treatment with BPO-HGG for 24 h in vitro inhibited BPO-KLH-induced lymphocyte proliferation and LMF release. Treatment with either HGG, dinitrophenylated HGG, BPO-KLH, or BPO-human serum albumin failed to abrogate T-cell lymphocyte proliferation of human lymphocytes in vitro. The antigen specificity of the reduced immunologic responsiveness was further demonstrated by the observation that lymphocytes treated with BPO-HGG for 24 h in vitro responded normally to tetanus toxoid antigen. The data suggest that conjugates of BPO-HGG induce hapten-specific helper T-cell unresponsiveness in vitro. PMID:6157701

Response to phytohaemagglutinin of lymphocytes from mice treated with anti-lymphocyte globulin

PubMed Central

Tursi, A.; Greaves, M. F.; Torrigiani, G.; Playfair, J. H. L.; Roitt, I. M.

1969-01-01

Thymus, spleen, lymph node and peripheral blood lymphocytes taken from mice treated with anti-lymphocyte globulin (ALG) showed a greatly diminished response to PHA in vitro. Recovery of circulating lymphocyte levels preceded recovery of responsiveness to PHA. The latter could be prevented by reinjection of ALG or by thymectomy. Grafts were rejected within a period equal to the normal rejection time after PHA responsiveness had recovered to a value of approximately 20 per cent of the normal. Thus the effect of ALG on thymus dependent lymphocytes in mice can be monitored by assessing the PHA sensitivity of peripheral white blood cells. ImagesFIG. 1 PMID:4900922

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

PubMed

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

2016-06-01

There are no accurate reference ranges for hematology parameters and lymphocyte subsets in Korean native beef cattle (Hanwoo). This study was performed to establish reliable reference ranges of hematology and lymphocyte subsets using a large number of Hanwoo cattle (n = 350) and to compare differences between Hanwoo and Holstein dairy cattle (n = 334). Additionally, age-related changes in lymphocyte subsets were studied. Bovine leukocyte subpopulation analysis was performed using mono or dual color flow cytometry. The leukocyte subpopulations investigated in healthy cattle included: CD2(+) cells, sIgM(+) cells, MHC class II(+) cells, CD3(+) CD4(+) cells, CD3(+) CD8(+) cells, and WC1(+) cells. Although Hanwoo and Holstein cattle are the same species, results showed several differences in hematology and lymphocyte subsets between Hanwoo and Holstein cattle. This study is the first report to establish reference ranges of hematology and lymphocyte subsets in adult Hanwoo cattle. © 2015 Japanese Society of Animal Science.

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

ClinicalTrials.gov

2018-01-26

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

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

PubMed Central

Kaplan, Kara; Echert, Ashley E.; Massat, Ben; Puissant, Madeleine M.; Palygin, Oleg; Geurts, Aron M.

2016-01-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DATph2−/−) rats. DATph2−/− rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DATph2−/− rats. Body temperature was also maintained in adult DATph2−/− rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DATph2−/− rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

"When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

PubMed

Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

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

PubMed Central

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

2014-01-01

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely ‘normalizing’ the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. PMID:25070512

Molecular mechanisms of lymphocyte extravasation. II. Studies of in vitro lymphocyte adherence to high endothelial venules.

PubMed

Braaten, B A; Spangrude, G J; Daynes, R A

1984-07-01

Lymphocyte migration from the blood into the lymph nodes in most species occurs across post-capillary high endothelial venules (HEV). In a previous study, we proposed that lymphocyte extravasation involves receptor-mediated binding followed by adenylate cyclase-dependent activation of lymphocyte motility. This hypothesis was, in part, based on observations of in vitro lymphocyte adherence to HEV by employing pertussigen, which is a known inhibitor of lymphocyte recirculation. In vitro lymphocyte-HEV binding requires a cold (6 degrees C) incubation step and binding is poor to nil if the assay is attempted at room (23 degrees C) or physiologic temperature. We decided to investigate why this assay is temperature restricted, because of the possibility that pertussigen or fucoidin -treated lymphocytes might interact with HEV differently at higher temperatures. We now report that O.C.T. compound (OCT), the embedding matrix generally used to cut frozen lymph node sections, is toxic to lymphocytes at temperatures above 6 degrees C. Exclusion of OCT from the assay system will allow lymphocyte-HEV binding to occur at 23 degrees C and to a lesser extent at 37 degrees C. With this modified protocol, lymphocytes treated with either pertussigen, fucoidin , or neuraminidase were tested for adherence to HEV at 23 degrees C. No essential difference in binding properties was observed from what had been reported at 6 degrees C. In contrast, trypsin-treated lymphocytes that did not bind to HEV with the standard technique at 6 degrees C did adhere to a minimal extent to HEV at 23 degrees C using the modified procedure. We also report some preliminary work, using the modified assay, on in vitro lymphocyte-HEV binding of rat, rabbit, and guinea pig lymphocytes to sections of lymph nodes from the respective species.

Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat.

PubMed

Legendre, Audrey; Elie, Christelle; Ramambason, Camille; Manens, Line; Souidi, Maamar; Froment, Pascal; Tack, Karine

2016-08-10

Environmental toxicant exposure can induce disorders in sex steroidogenesis during fetal gonad development. Our previous study demonstrated that chronic adult exposure to a supra environmental concentration of depleted uranium (DU) does not impair testicular steroidogenesis in rats. In this study, we investigated the effects of lifelong exposure (embryo - adult) to low-dose DU (40 or 120mgL -1 ) on adult rat testicular steroidogenesis and spermatogenesis. A significant content of uranium was detected in testis and epididymis in the DU 120mgL -1 group and the assay in epididymal spermatozoa showed a significant content in both groups. No major defect was observed in testicular histology except a decrease in the number of basal vacuoles in the DU groups. Moreover, plasma Follicle-Stimuling Hormone [FSH] and Luteinizing Hormone [LH] levels were increased only in the DU 120mgL -1 group and intratesticular estradiol was decreased in both groups. Testosterone level was reduced in plasma and testis in the DU 40mgL -1 group. These modulations could be explained by an observed decrease in gene expression of luteinizing hormone receptor (LHR), and enzymes involved in steroid production and associated signal transduction (StAR, cyp11a1, cyp17a1, 3βhsd, 17βhsd, TGFβ1, AR). Several genes specific to germ cells and cell junctions of the blood-testis barrier were also modulated. In conclusion, these data show that fetal life is a critical window for chronic uranium exposure and that the endocrine activities of low-dose uranium could disrupt steroidogenesis through the hypothalamic-pituitary-testicular axis. Further investigation should be so useful in subsequent generations to improve risk assessment of uranium exposure. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Intestinal lymphocyte subsets and turnover are affected by chronic alcohol consumption: implications for SIV/HIV infection.

PubMed

Poonia, Bhawna; Nelson, Steve; Bagby, Greg J; Veazey, Ronald S

2006-04-15

We recently demonstrated that simian immunodeficiency virus (SIV) viral loads were significantly higher in the plasma of rhesus macaques consuming alcohol compared with controls following intrarectal SIV infection. To understand the possible reasons behind increased viral replication, here we assessed the effects of chronic alcohol consumption on distribution and cycling of various lymphocyte subsets in the intestine. Macaques were administered alcohol (n = 11) or sucrose (n = 12), and percentages of memory and naive and activated lymphocyte subsets were compared in the blood, lymph nodes, and intestines. Although minimal differences were detected in blood or lymph nodes, there were significantly higher percentages of central memory (CD95+CD28+) CD4+ lymphocytes in the intestines from alcohol-receiving animals before infection compared with controls. In addition, higher percentages of naive (CD45RA+CD95-) as well as CXCR4+CD4 cells were detected in intestines of alcohol-treated macaques. Moreover, alcohol consumption resulted in significantly lower percentages of effector memory (CD95+CD28-) CD8 lymphocytes as well as activated Ki67+CD8 cells in the intestines. A subset (7 receiving alcohol and 8 receiving sucrose) were then intrarectally inoculated with SIV(mac251). Viral RNA was compared in different tissues using real-time PCR and in situ hybridization. Higher levels of SIV replication were observed in tissues from alcohol-consuming macaques compared with controls. Central memory CD4 lymphocytes were significantly depleted in intestines and mesenteric lymph nodes from all alcohol animals at 8 weeks postinfection. Thus, changes in the mucosal immune compartment (intestines) in response to alcohol are likely the major reasons behind higher replication of SIV observed in these animals.

Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting CCAAT/enhancer-binding protein beta (C/EBP beta) expression.

PubMed

Selim, Erin; Frkanec, Julie T; Cunard, Robyn

2007-02-01

Fibrates, which function by binding and activating peroxisome proliferator-activated receptor alpha (PPARalpha), have been used successfully to treat hyperlipidemia and atherosclerosis. Increasing evidence suggests that in addition to their lipid lowering activities these medications also function as immunosuppressive agents. Tribbles is a Drosophila protein that slows cell cycle progression, and its mammalian homolog, TRB3 interferes with insulin-induced activation of AKT. In these studies we demonstrate that fibrates upregulate TRB3 expression in mitogen-activated lymphocytes. Interestingly, in lymphocytes fibrates augment TRB3 expression in both PPARalpha wildtype and knockout mice, suggesting that upregulation of this protein occurs in a PPARalpha-independent manner. Fibrates activate a proximal TRB3 promoter construct and mutation or partial deletion of a potential PPAR response element does not alter the ability of fibrates to drive TRB3 expression. Subsequent studies reveal that fibrates upregulate C/EBPbeta and CHOP in lymphocytes and mutation of potential C/EBPbeta and CHOP consensus sequences abrogates the ability of fibrates to upregulate TRB3 promoter activity. Accordingly, fibrates enhance the recruitment of C/EBPbeta and CHOP to the proximal TRB3 promoter. Finally, TRB3 expression in lymphocytes induces G2 cell cycle delay and cellular depletion. These studies outline a novel PPARalpha-independent mechanism of action of fibrates and document for the first time the expression of TRB3 in activated lymphocytes.

Lymphocytic esophagitis: Report of three cases and review of the literature

PubMed Central

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

Depressive Symptoms, Depletion, or Developmental Change? Withdrawal, Apathy, and Lack of Vigor in the Geriatric Depressive Scale.

ERIC Educational Resources Information Center

Adams, Kathryn Betts

2001-01-01

This study has dual goals of confirming the existence of a "Withdrawal/Apathy/[Lack of] Vigor" (WAV) dimension of the Geriatric Depression Scale (GDS) and determining if it is descriptive of either depletion or disengagement-related change in older adults. High endorsement rates suggest WAV may be congruent with disengagement or depletion and may…

The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma.

PubMed

Buettner, Stefan; Spolverato, Gaya; Kimbrough, Charles W; Alexandrescu, Sorin; Marques, Hugo P; Lamelas, Jorge; Aldrighetti, Luca; Gamblin, T Clark; Maithel, Shishir K; Pulitano, Carlo; Weiss, Matthew; Bauer, Todd W; Shen, Feng; Poultsides, George A; Marsh, J Wallis; IJzermans, Jan N M; Koerkamp, Bas Groot; Pawlik, Timothy M

2018-06-11

Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival

Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

ClinicalTrials.gov

2017-10-10

Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia

PubMed Central

Gribben, John G.; Zahrieh, David; Stephans, Katherine; Bartlett-Pandite, Lini; Alyea, Edwin P.; Fisher, David C.; Freedman, Arnold S.; Mauch, Peter; Schlossman, Robert; Sequist, Lecia V.; Soiffer, Robert J.; Marshall, Blossom; Neuberg, Donna; Ritz, Jerome; Nadler, Lee M.

2005-01-01

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens. PMID:16131571

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

USDA-ARS?s Scientific Manuscript database

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

Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

PubMed

Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

2015-08-01

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

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

PubMed

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

2014-09-01

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma.

PubMed

Schober, Sebastian J; von Luettichau, Irene; Wawer, Angela; Steinhauser, Maximilian; Salat, Christoph; Schwinger, Wolfgang; Ussowicz, Marek; Antunovic, Petar; Castagna, Luca; Kolb, Hans-Jochem; Burdach, Stefan E G; Thiel, Uwe

2018-04-27

Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 × 10 4 to 1 × 10 8 CD3 + cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia.

PubMed

Deeks, Emma D

2017-02-01

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

Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

PubMed Central

D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

2012-01-01

Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

PubMed Central

Simpson, Tyler R.; Li, Fubin; Montalvo-Ortiz, Welby; Sepulveda, Manuel A.; Bergerhoff, Katharina; Arce, Frederick; Roddie, Claire; Henry, Jake Y.; Yagita, Hideo; Wolchok, Jedd D.; Peggs, Karl S.; Ravetch, Jeffrey V.

2013-01-01

Treatment with monoclonal antibody specific for cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, has emerged as an effective therapy for the treatment of metastatic melanoma. Although subject to debate, current models favor a mechanism of activity involving blockade of the inhibitory activity of CTLA-4 on both effector (T eff) and regulatory (T reg) T cells, resulting in enhanced antitumor effector T cell activity capable of inducing tumor regression. We demonstrate, however, that the activity of anti–CTLA-4 antibody on the T reg cell compartment is mediated via selective depletion of T reg cells within tumor lesions. Importantly, T reg cell depletion is dependent on the presence of Fcγ receptor–expressing macrophages within the tumor microenvironment, indicating that T reg cells are depleted in trans in a context-dependent manner. Our results reveal further mechanistic insight into the activity of anti-CTLA-4–based cancer immunotherapy, and illustrate the importance of specific features of the local tumor environment on the final outcome of antibody-based immunomodulatory therapies. PMID:23897981

Asset Depletion, Chronic Financial Stress, and Mortgage Trouble Among Older Female Homeowners.

PubMed

Castro Baker, Amy; West, Stacia; Wood, Anna

2017-09-08

The Great Recession disproportionately impacted older adults and women of color, suggesting that women may be entering retirement without adequate assets. However, the current literature lacks a detailed account of women's experiences of mortgage trouble and foreclosure, as well as a longitudinal view of how these experiences impacted their overall financial assets. Grounded in cumulative inequality theory, this mixed methods study employed a QUAL→quan approach to gather qualitative data from a sample of 21 older adult women regarding their experiences of mortgage trouble. Quantitative longitudinal data was gathered for a subsample of the Early Baby Boomer Cohort using the Health and Retirement Study. Qualitative findings indicated women approaching retirement experienced chronic underemployment, wage stagnation, and financial volatility as contributors to asset depletion and eventual mortgage default or foreclosure. Quantitative results indicated asset depletion both during and post-Recession was considerably more pronounced among older adult women of color compared to older adult White men. These findings suggest that a lifetime of financial disadvantage coupled with macroeconomic instability situates older adult women, particularly women of color, in a financially vulnerable position for retirement. The ways in which 2017 attacks on the Consumer Financial Protection Bureau, Dodd-Frank, and the Fiduciary rule carry potential to further destabilize this population are also discussed. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats.

PubMed

Nelson, Lars H; Lenz, Kathryn M

2017-01-01

Microglia, the innate immune cells of the central nervous system, regulate brain development by promoting cell genesis, pruning synapses, and removing dying, newly-born or progenitor cells. However, the role of microglia in the early life programming of behavior under normal conditions is not well characterized. We used central infusion of liposomal clodronate to selectively deplete microglia from the neonatal rat brain and subsequently assessed the impact of microglial depletion on programming of juvenile and adult motivated behaviors. Liposomal clodronate treatment on postnatal days one and four led to greater than 70% loss of forebrain microglia by postnatal day 6 that lasted for approximately ten days. Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior on the elevated plus maze and open field test, and increased locomotor activity. On a test of juvenile social play, microglial depletion led to decreased chase behaviors relative to control animals. There was no change in active social behavior in adults on a reciprocal social interaction test, but there was decreased passive interaction time and an increased number of social avoidance behaviors in clodronate treated rats relative to controls. There was an overall decrease in behavioral despair on the forced swim test in adult rats treated neonatally with clodronate. Females, but not males, treated neonatally with clodronate showed a blunted corticosterone response after acute stress in adulthood. These results show that microglia are important for the early life programming of juvenile and adult motivated behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

PubMed Central

Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

2012-01-01

While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4+ T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT. PMID:22205732

Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization.

PubMed

Berki, T; Németh, P

1998-02-01

An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs. host reaction.

Deregulation of Apoptosis - Is it Still an Important Issue in Pathogenesis of Chronic Lymphocytic Leukemia?

PubMed

Podhorecka, Monika; Macheta, Arkadiusz; Bozko, Maria; Bozko, Andrzej; Malek, Nisar P; Bozko, Przemyslaw

2016-01-01

Chronic lymphocytic leukemia (CLL), a clonal expansion of B CD5+ cells, is the most common type of adult leukemia in western countries. The accumulation of neoplastic B-cells is primarily caused by prolonged life-span of these cells due to deregulation of apoptosis, and only marginally due to a higher proliferation rate. In spite of numerous reports characterizing particular mechanisms of B-CLL cell apoptosis, still relatively little is known about the complex regulation of this process. Therefore, more detailed research is required to understand the complicated mechanisms and regulatory processes of apoptosis in neoplastic B lymphocytes.

Water Depletion Threatens Agriculture

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

DHT and IGF-1 in peripheral blood lymphocytes: new markers for the biological passport of athletes.

PubMed

Mancini, A; Imperlini, E; Alfieri, A; Spaziani, S; Martone, D; Parisi, A; Orru, S; Buono, P

2013-01-01

We performed a pilot study using human peripheral blood lymphocytes (PBL) as a novel system to identify new biomarkers of dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-1) abuse in sport. First, to obtain a gene signature, we treated cultures of lymphocytes from sedentary males with three doses of 0.237 microg/ml DHT, each of which is 80-fold the physiological concentration in young adult male serum, at days 0, 2 and 4, or with a single dose of 1.25 microg/ml IGF-1, which is 5-fold the physiological concentration in young adult male serum. We then used the Human Genome U133 Plus 2.0 microarray to identify a gene signature related to DHT or IGF-1 administration. Gene expression was evaluated after 7 and 21 days of DHT treatment, and after 24 h, 72 h and 7 days of IGF-1 treatment. Microarray analysis yielded a list of genes whose expression was altered after DHT or IGF-1 treatment. Among these we selected the genes that are most representative of the pathways associated with skeletal and muscular disorders using the IPA bioinformatics tool. We identified six (IDO1, CXCL13, CCL1, GZMB, VDR and IL2RA) and two (FN1 and RAB31) genes that were up-regulated in lymphocytes from sedentary subjects after 7 days of DHT and IGF-1 treatment, respectively. The expression of these genes in lymphocytes from differently trained athletes was either down-regulated or similar to that in lymphocytes from sedentary subjects. This finding suggests that up-regulation was due to the drug and not to physical exercise. In conclusion, we demonstrate that PBL can be useful in anti-doping checks, and we describe new biomarkers of DHT and IGF-1 abuse which can be included in the Athlete's Biological Passport.

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

ClinicalTrials.gov

2013-09-27

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

Lymphocyte responses to phytohaemagglutinin: age-related effects.

PubMed Central

Fernandez, L A; MacSween, J M; Langley, G R

1976-01-01

Cell-mediated immunity is depressed in elderly individuals compared to young individuals, and lymphocytes from elderly individuals have been reported to have impaired lymphocyte responsiveness to stimulation by PHA after 4 days of culture. We have confirmed this observation. However, after 8 days of culture, the lymphocyte responses were greater in elderly normal individuals than in young normal individuals. Responses of lymphocytes from young individuals decreased with time from 4 to 8 days in culture, while there were increased responses with time when lymphocytes from elderly individuals were studied. When adherent cells from lymphocytes of young individuals were removed by passage through protein-coated Degalan-bead columns, the lymphocyte responses to PHA were significantly increased at 8 days. Passage of lymphocytes from elderly individuals through coated Degalan bead columns did not alter the lymphocyte responses. Removal of macrophages from the mononuclear cells obtained from young individuals did not result in increased lymphocyte responses to PHA after 8 days in culture. Removal of adherent cells appeared to have the same effect regardless of the efficiency of removing B cells. The adherent cells removed by the protein coated columns, therefore, appear to be nonphagocytic mononuclear cells which are not B lymphocytes. PMID:1086285

Lymphocyte-platelet crosstalk in Graves' disease.

PubMed

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

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

“When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

PubMed Central

Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

Ocrelizumab: a B-cell depleting therapy for multiple sclerosis.

PubMed

Jakimovski, Dejan; Weinstock-Guttman, Bianca; Ramanathan, Murali; Kolb, Channa; Hojnacki, David; Minagar, Alireza; Zivadinov, Robert

2017-09-01

Multiple sclerosis (MS) is the most common neurological disease responsible for early disability in the young working population. In the last two decades, based on retrospective/prospective data, the use of disease-modifying therapies has been shown to slow the rate of disability progression and prolonged the time to conversion into secondary-progressive MS (SPMS). However, despite the availability of several approved therapies, disability progression cannot be halted significantly in all MS patients. Areas covered: This article reviews the immunopathology of the B-cells, and their role in pathogenesis of MS and their attractiveness as a potential therapeutic target in MS. The review focuses on the recently published ocrelizumab phase III trials in terms of its efficacy, safety, and tolerability as well as its future considerations. Expert opinion: B lymphocyte cell depletion therapy offers a compelling and promising new option for MS patients. Nonetheless, there is a need for heightened vigilance and awareness in detecting potential long-term consequences that currently remain unknown.

Preterm Infants Have Deficient Monocyte and Lymphocyte Cytokine Responses to Group B Streptococcus▿

PubMed Central

Currie, Andrew J.; Curtis, Samantha; Strunk, Tobias; Riley, Karen; Liyanage, Khemanganee; Prescott, Susan; Doherty, Dorota; Simmer, Karen; Richmond, Peter; Burgner, David

2011-01-01

Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection. PMID:21300777

Reprogramming T cell Lymphocytes to Induced Pluripotent Stem Cells

NASA Astrophysics Data System (ADS)

Bared, Kalia

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

Adipose tissue lymphocytes: types and roles.

PubMed

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

2009-12-01

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

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

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

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

Depletion of CD4⁺ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques.

PubMed

Ortiz, Alexandra M; Klatt, Nichole R; Li, Bing; Yi, Yanjie; Tabb, Brian; Hao, Xing Pei; Sternberg, Lawrence; Lawson, Benton; Carnathan, Paul M; Cramer, Elizabeth M; Engram, Jessica C; Little, Dawn M; Ryzhova, Elena; Gonzalez-Scarano, Francisco; Paiardini, Mirko; Ansari, Aftab A; Ratcliffe, Sarah; Else, James G; Brenchley, Jason M; Collman, Ronald G; Estes, Jacob D; Derdeyn, Cynthia A; Silvestri, Guido

2011-11-01

CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte-depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell-mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

Lymphocytes with Immunoglobulin E Fc Receptors in Patients with Atopic Disorders

PubMed Central

Spiegelberg, H. L.; O'Connor, R. D.; Simon, R. A.; Mathison, D. A.

1979-01-01

Lymphocytes from normal nonallergic donors and patients with atopic disorders were analyzed for subpopulations bearing Fc receptors for immunoglobulin (Ig)E (Fcε) and IgG (Fcγ), surface IgM (sIgM) and IgD (sIgD), and for T cells forming spontaneous rosettes with sheep erythrocytes (E). The patients were divided into three groups according to serum IgE concentrations and systemic corticosteroid treatment. Group I consisted of 12 atopic patients with either normal or moderately increased IgE levels up to 4,000 U/ml. Four patients of group II and three of group III had 10,500-31,000 U/ml and severe atopic dermatitis. Patients of group III, but not I and II, were receiving corticosteroids systemically. The percentage (mean ±SD) and total number of Fcε+ lymphocytes were 1.2±0.5%, 41±24/mm3 in 12 normals; 1.6±0.9%, 59±43/mm3 in patients of group I: 7.0±2.0%, 187±67/mm3 in group II; and 0.3±0.1%, 13±5/mm3 in patients of group III. The increase in group II and decrease in group III of Fcε+ cells were statistically significantly different from the normal persons and patients of group I. In contrast, the patients did not differ significantly from the donors in sIgM+, sIgD+, Fcγ+, and E+ cell populations. As shown by depletion of sIg+ cells in four patients with atopic disorders, the great majority of the Fcε+ lymphocytes were B cells. However, two patients with elevated Fcε+ cell numbers had small numbers of mixed E- and Fcε-rosetting cells, presumably T cells. Two patients of group II were examined during an acute herpes simplex infection. Both showed an ≅80% decrease of Fcε+ cells at that time. No apparent correlation between numbers of Fcε+ cells and IgE level existed in patients of group I. Injection of an IgE myeloma protein into two monkeys did not significantly change their percentages of Fcε+ lymphocytes. The data indicate that Fcε+ lymphocytes are increased in patients with markedly elevated serum IgE and severe atopic disease, suggesting that

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

ClinicalTrials.gov

2018-03-05

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

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

PubMed

Smetana, K; Karban, J; Trneny, M

2010-01-01

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

Spotlight on ibrutinib and its potential in frontline treatment of chronic lymphocytic leukemia

PubMed Central

Khan, Maliha; Gibbons, Jamie L; Ferrajoli, Alessandra

2017-01-01

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the adult population. Current efforts are focused on better understanding the intricate pathophysiology of the disease to develop successful targeted therapies. Ibrutinib is emerging as an important agent in this new age of targeted treatment for CLL. As a Bruton’s tyrosine kinase inhibitor, it blocks the signaling pathway that malignant B-lymphocytes need for growth and maturation. Ibrutinib’s role in therapy was further expanded recently when the US Food and Drug Administration approved its use in both frontline and salvage treatment for patients with CLL. This review assesses the effectiveness of ibrutinib in the frontline setting, its efficacy in various types of patients with CLL, and its safety and tolerability. PMID:28408842

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

PubMed

Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

2017-10-01

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

Role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, A.; Morse, H.C. III; Winkelstein, J.

1978-07-01

The avirulent high egg passage (HEP) strain of rabies virus produces an inapparent infection limited to the central nervous system (CNS) in intracerebrally inoculated adult mice. Heavy chain isotype (anti-..mu.. antiserum) immunosuppression potentiates the infection, with a mortality of about 60% and with elevated virus titers in the brain. Anti-..mu..-treated mice fail to raise antibody responses to rabies virus although their T cell function is normal when measured by the concanavalin A response of splenic lymphocytes. This indicates that the B cell response plays an important role in clearance of rabies virus from the neuroparenchyma. Treatment with cyclophosphamide or bymore » adult thymectomy, x-irradiation, and bone marrow reconstitution potentiates HEP infection to a greater extent than does isotype supression. Since these suppressive techniques impair both T and B lymphocyte responses, the data suggest that cellular immune mechanisms may also contribute to host defenses against this central nervous system (CNS) virus infection.« less

Hypergravity-induced immunomodulation in a rodent model: lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Pecaut, Michael J.; Green, Lora M.; Miller, Glen M.; Nelson, Gregory A.

2002-01-01

The major goal of this study was to quantify changes in lymphoid organs and cells over time due to centrifugation-induced hypergravity. C57BL/6 mice were exposed to 1, 2 and 3 G and the following assays were performed on days 1, 4, 7, 10, and 21: spleen, thymus, lung, and liver masses; total leukocyte, lymphocyte, monocyte/macrophage, and granulocyte counts; level of splenocyte apoptosis; enumeration of CD3+ T, CD3+/CD4+ T helper, CD3+/CD8+ T cytotoxic, B220+ B, and NK1.1+ natural killer cells; and quantification of cells expressing CD25, CD69, and CD71 activation markers. The data show that increased gravity resulted in decreased body, spleen, thymus, and liver, but not lung, mass. Significant reductions were noted in all three major leukocyte populations (lymphocytes, granulocytes, monocyte/macrophages) [correction of macrphages] with increased gravity; persistent depletion was noted in blood but not spleen. Among the various lymphocyte populations, the CD3+/CD8+ T cells and B220+ B cells were the most affected and NK1.1+ NK cells the least affected. Overall, the changes were most evident during the first week, with a greater influence noted for cells in the spleen. A linear relationship was found between some of the measurements and the level of gravity, especially on day 4. These findings indicate that hypergravity profoundly alters leukocyte number and distribution in a mammalian model and that some aberrations persisted throughout the three weeks of the study. In certain cases, the detected changes were similar to those observed after whole-body irradiation. In future investigations we hope to combine hypergravity with low-dose rate irradiation and immune challenge.

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

ClinicalTrials.gov

2017-08-09

Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

Lymphocyte changes in beta-thalassaemia major.

PubMed Central

Musumeci, S; Schiliro, G; Romeo, M A; Sciotto, A; Rosalba, A; Pizzarelli, G

1979-01-01

Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls. PMID:316991

Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats

PubMed Central

2016-01-01

Abstract Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyperlocomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator odor–induced avoidance behavior, but increased their risk assessment behaviors compared with vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits—behavioral disinhibition and locomotion—as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development of juvenile and adult behavior. PMID:27957532

THE LYMPHOCYTE RESPONSE TO PRIMARY MOLONEY SARCOMA VIRUS TUMORS IN BALB/c MICE

PubMed Central

Lamon, E. W.; Wigzell, H.; Klein, E.; Andersson, B.; Skurzak, H. M.

1973-01-01

Adult BALB/c mice were injected with Moloney sarcoma virus (MSV) after which the animals' lymphocytes were examined for activity against Moloney leukemia virus (MLV) antigen-bearing target cells at 5-day intervals for 30 days. Lymphocytes from these animals and appropriately matched controls were fractionated into B cell-deficient (primarily T cells) and T cell-deficient (primarily B cells) subpopulations. Macrophages were removed using iron powder and magnetism. The unfractionated lymphocytes, T cells, and non-T cells were then tested in microcytotoxicity tests. Antigen-specific activity was found in the unfractionated lymphocytes from animals that had not yet developed palpable tumors and from regressor animals. The T cells were active just before tumor development and just after regression; however, by day 30 after virus infection (8–10 days after regression) the T cell subpopulation was much less active. The non-T cell subpopulation was also active before tumor development and soon after regression. However, this activity continued to rise after regression and was highest at 30 days. At day 15 (peak tumor size) neither subpopulation was active. The activity was demonstrated to be specific for the MLV-determined cell surface antigen by testing on control target cells that were MLV antigen negative and by comparison of the inhibitory effects with lymphocytes immune to a nonpertinent antigen as well as normal lymphocytes. The non-T cells were tested for activity before and after removal of macrophages with iron powder and magnetism. Such cells were significantly more active after removal of the macrophages. These data demonstrate specific T cell and non-T cell activity in microcytotoxicity tests with a tumor-specific system and strongly suggest that the non-T cell activity described herein is a B cell function. PMID:4709269

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

PubMed

Li, Qiong; Wang, Zhenhong

2016-08-01

An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Comparative cytotoxicity and genotoxicity of cobalt (II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro.

PubMed

Rajiv, S; Jerobin, J; Saranya, V; Nainawat, M; Sharma, A; Makwana, P; Gayathri, C; Bharath, L; Singh, M; Kumar, M; Mukherjee, A; Chandrasekaran, N

2016-02-01

Despite the extensive use of nanoparticles (NPs) in various fields, adequate knowledge of human health risk and potential toxicity is still lacking. The human lymphocytes play a major role in the immune system, and it can alter the antioxidant level when exposed to NPs. Identification of the hazardous NPs was done using in vitro toxicity tests and this study mainly focuses on the comparative in vitro cytotoxicity and genotoxicity of four different NPs including cobalt (II, III) oxide (Co3O4), iron (III) oxide (Fe2O3), silicon dioxide (SiO2), and aluminum oxide (Al2O3) on human lymphocytes. The Co3O4 NPs showed decrease in cellular viability and increase in cell membrane damage followed by Fe2O3, SiO2, and Al2O3 NPs in a dose-dependent manner after 24 h of exposure to human lymphocytes. The oxidative stress was evidenced in human lymphocytes by the induction of reactive oxygen species, lipid peroxidation, and depletion of catalase, reduced glutathione, and superoxide dismutase. The Al2O3 NPs showed the least DNA damage when compared with all the other NPs. Chromosomal aberration was observed at 100 µg/ml when exposed to Co3O4 NPs and Fe2O3 NPs. The alteration in the level of antioxidant caused DNA damage and chromosomal aberration in human lymphocytes. © The Author(s) 2015.

[Cystinosis : Diagnosis, cystine-depleting therapy, and transition].

PubMed

Kaufeld, Jessica; Weber, Lutz T; Kurschat, Christine; Canaan-Kuehl, Sima; Brand, Eva; Oh, Jun; Pape, Lars

2018-04-18

This article presents a case of cystinosis in a young man. Diagnosis of the disease and the problem of transition to adult care are described. Cystinosis is a rare lysosomal storage disease with first manifestation in early childhood presenting as renal Fanconi syndrome. Without treatment, the disease leads to severe health impairment. Due to the rarity of the disease, a correct diagnosis is often delayed. Without treatment, cystinosis often leads to end-stage renal failure, blindness, hypothyroidism, diabetes mellitus, and rickets. Cystine-depleting therapy with cysteamine significantly improves mortality and quality of life.

Opinion: Interactions of innate and adaptive lymphocytes

PubMed Central

Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

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

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

PubMed

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] < 1/h total sleep time [TST]), mild OSA (1 ≤ AHI < 5/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

In vitro induction of lymphocyte responsiveness by a Strongylus vulgaris-derived mitogen.

PubMed

Bailey, M; Lloyd, S; Martin, S C; Soulsby, E J

1984-01-01

Proliferation in vitro of peripheral blood lymphocytes both from horses infected with Strongylus vulgaris and from helminth-free ponies was observed in the presence of extracts of the fourth and fifth stage larvae and adults of S. vulgaris. In addition, S. vulgaris extracts induced transformation in cultures of peripheral blood lymphocytes from sheep and dogs and in mouse spleen cell cultures. Nylon wool non-adherent, T cell enriched fractions of lymphocytes from both mice and horses were stimulated by the S. vulgaris larval mitogen while no proliferation was observed in cultures containing nylon wool adherent, B cell enriched fractions. Macrophage co-operation appeared not to be necessary for S. vulgaris mitogen-induced transformation of spleen cells. The S. vulgaris mitogen stimulated a subpopulation of mouse spleen cells different from those responsive to PHA, Con A and LPS. These cells might be T helper cells since B cells were stimulated to proliferate in the presence of both T cells and S. vulgaris larval mitogen. In addition, the supernatant of in vitro cultured larvae of S. vulgaris induced slight, but significant transformation of equine peripheral blood lymphocytes. Therefore, it is possible that the S. vulgaris mitogen released by both viable parasites and degenerating larvae might induce T cell dependent production of immunoglobulin in vivo and account for the beta-globulinaemia, of which IgG(T) is a major component, in S vulgaris infected horses.

The Optimal Cut-Off Value of Neutrophil-to-Lymphocyte Ratio for Predicting Prognosis in Adult Patients with Henoch–Schönlein Purpura

PubMed Central

Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

2016-01-01

Background The development of gastrointestinal (GI) bleeding and end-stage renal disease (ESRD) can be a concern in the management of Henoch–Schönlein purpura (HSP). We aimed to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of adult patients with HSP. Methods Clinical data including the NLR of adult patients with HSP were retrospectively analyzed. Patients were classified into three groups as follows: (a) simple recovery, (b) wax & wane without GI bleeding, and (c) development of GI bleeding. The optimal cut-off value was determined using a receiver operating characteristics curve and the Youden index. Results A total of 66 adult patients were enrolled. The NLR was higher in the GI bleeding group than in the simple recovery or wax & wane group (simple recovery vs. wax & wane vs. GI bleeding; median [IQR], 2.32 [1.61–3.11] vs. 3.18 [2.16–3.71] vs. 7.52 [4.91–10.23], P<0.001). For the purpose of predicting simple recovery, the optimal cut-off value of NLR was 3.18, and the sensitivity and specificity were 74.1% and 75.0%, respectively. For predicting development of GI bleeding, the optimal cut-off value was 3.90 and the sensitivity and specificity were 87.5% and 88.6%, respectively. Conclusions The NLR is useful for predicting development of GI bleeding as well as simple recovery without symptom relapse. Two different cut-off values of NLR, 3.18 for predicting an easy recovery without symptom relapse and 3.90 for predicting GI bleeding can be used in adult patients with HSP. PMID:27073884

Association of immunophenotypic characterization of peripheral lymphocytes with different clinical phenotypes of tuberculosis in Chinese Han children.

PubMed

Xiao, Jing; Sun, Lin; Wu, Xi-Rong; Miao, Qing; Jiao, Wei-Wei; Shen, Chen; Shen, Dan; Feng, Wei-Xing; Liu, Fang; Shen, A-Dong

2012-01-01

Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB. In this study, we obtained blood samples from 114 Chinese pediatric TB patients and 116 matched controls to study the association of phenotypic subsets of peripheral lymphocytes with different clinical phenotypes of TB. The subjects were classified as the control group and the TB patients group which were further divided into a pulmonary TB group and an extra-pulmonary TB group (more serious than the former). The distribution of lymphocyte subpopulations, including T lymphocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes, B lymphocytes, and natural killer (NK) cells, were quantitatively analyzed by flow cytometry. Compared to the healthy controls, TB infection was associated with significantly higher B cell (P < 0.0001), and lower T cell (P = 0.029) and NK cell (P < 0.0001) percentages. Compared to pulmonary TB patients, extra-pulmonary TB was associated with relatively higher B cell (P = 0.073), and lower T cell percentages (P = 0.021), higher purified protein derivative (PPD) negative rate (P = 0.061), and poorer PPD response (P = 0.010). Most pulmonary TB cases were primary pulmonary TB (89.1%), and most extra-pulmonary TB cases had TB meningitis (72.1%). This study demonstrates changes in the lymhocyte distribution in children suffering from different clinical phenotypes of TB; such as primary pulmonary TB, and TB meningitis. These patterns may have significance in understanding the pathogenesis and prognostic markers of the disease, and for developing immunomodulatory modalities of therapy.

Characterization of CD31 expression on murine and human neonatal T lymphocytes during development and activation

PubMed Central

Fike, Adam J.; Nguyen, Linda T.; Kumova, Ogan K.; Carey, Alison J.

2017-01-01

Background CD31, expressed by the majority of the neonatal T cell pool, is involved in modulation of T-cell Receptor signalling by increasing the threshold for T cell activation. Therefore, CD31 could modulate neonatal tolerance and adaptive immune responses. Methods Lymphocytes were harvested from murine neonates at different ages, human late preterm and term cord blood, and adult peripheral blood. Human samples were activated over a five-day period to simulate acute inflammation. Mice were infected with influenza; lungs and spleens were harvested at days 6 and 9 post-infection and analyzed by flow cytometry. Results CD31 expressing neonatal murine CD4+ and CD8a+ T cells increase over the first week of life. Upon in vitro stimulation, human infants’ CD4+ and CD8a+ T cells shed CD31 faster in comparison to adults. In the context of acute infection, mice infected at 3-days old have an increased number of naive and activated CD31+ T lymphocytes at the site of infection at day 6 and 9 post-infection, as compared to 7-days old; however, the opposite is true in the periphery. Conclusion Differences in trafficking of CD31+ Cytotoxic T Lymphocytes (CTLs) during acute influenza infection could modulate tolerance and contribute to a dampened adaptive immune response in neonates. PMID:28355204

Ego depletion increases risk-taking.

PubMed

Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

2012-01-01

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

Oligodendrocytes and Progenitors Become Progressively Depleted within Chronically Demyelinated Lesions

PubMed Central

Mason, Jeffrey L.; Toews, Arrel; Hostettler, Janell D.; Morell, Pierre; Suzuki, Kinuko; Goldman, James E.; Matsushima, Glenn K.

2004-01-01

To understand mechanisms that may underlie the progression of a demyelinated lesion to a chronic state, we have used the cuprizone model of chronic demyelination. In this study, we investigated the fate of oligodendrocytes during the progression of a demyelinating lesion to a chronic state and determined whether transplanted adult oligodendrocyte progenitors could remyelinate the chronically demyelinated axons. Although there is rapid regeneration of the oligodendrocyte population following an acute lesion, most of these newly regenerated cells undergo apoptosis if mice remain on a cuprizone diet. Furthermore, the oligodendrocyte progenitors also become progressively depleted within the lesion, which appears to contribute to the chronic demyelination. Interestingly, even if the mice are returned to a normal diet following 12 weeks of exposure to cuprizone, remyelination and oligodendrocyte regeneration does not occur. However, if adult O4+ progenitors are transplanted into the chronically demyelinated lesion of mice treated with cuprizone for 12 weeks, mature oligodendrocyte regeneration and remyelination occurs after the mice are returned to a normal diet. Thus, the formation of chronically demyelinated lesions induced by cuprizone appears to be the result of oligodendrocyte depletion within the lesion and not due to the inability of the chronically demyelinated axons to be remyelinated. PMID:15111314

Clearance of Virulent but Not Avirulent Rhodococcus equi from the Lungs of Adult Horses Is Associated with Intracytoplasmic Gamma Interferon Production by CD4+ and CD8+ T Lymphocytes

PubMed Central

Hines, Stephen A.; Stone, Diana M.; Hines, Melissa T.; Alperin, Debby C.; Knowles, Donald P.; Norton, Linda K.; Hamilton, Mary J.; Davis, William C.; McGuire, Travis C.

2003-01-01

Rhodococcus equi is a gram-positive bacterium that infects alveolar macrophages and causes rhodococcal pneumonia in horses and humans. The virulence plasmid of R. equi appears to be required for both pathogenicity in the horse and the induction of protective immunity. An understanding of the mechanisms by which virulent R. equi circumvents protective host responses and by which bacteria are ultimately cleared is important for development of an effective vaccine. Six adult horses were challenged with either virulent R. equi or an avirulent, plasmid-cured derivative. By using a flow cytometric method for intracytoplasmic detection of gamma interferon (IFN-γ) in equine bronchoalveolar lavage fluid (BALF) cells, clearance of the virulent strain was shown to be associated with increased numbers of pulmonary CD4+ and CD8+ T lymphocytes producing IFN-γ. There was no change in IFN-γ-positive cells in peripheral blood, suggesting that a type 1 recall response at the site of challenge was protective. The plasmid-cured strain of R. equi was cleared in horses without a significant increase in IFN-γ-producing T lymphocytes in BALF. In contrast to these data, a previous report in foals suggested an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-γ expression by equine CD4+ T lymphocytes. Intracytoplasmic detection of IFN-γ provides a method to better determine whether modulation of macrophage-activating cytokines by virulent strains occurs uniquely in neonates and contributes to their susceptibility to rhodococcal pneumonia. PMID:12626444

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

PubMed

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

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

PubMed Central

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

2011-01-01

An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

Phylogeny of lymphocyte heterogeneity: the cellular requirements for the mixed leucocyte reaction with channel catfish.

PubMed Central

Miller, N W; Deuter, A; Clem, L W

1986-01-01

Vigorous mixed leucocyte reactions (MLR) were obtained using channel catfish peripheral blood leucocytes (PBL) when equal numbers of responder and stimulator cells (5 X 10(5) cells each) were cocultured. The use of 2000 rads of X-irradiation was sufficient to block subsequent proliferative responses of the stimulator cells. The cellular requirements for channel catfish MLR responses were assessed by using three functionally distinct leucocyte subpopulations isolated from the PBL. B cells (sIg+ lymphocytes) and T cells (sIg- lymphocytes) were isolated by an indirect panning procedure employing a monoclonal antibody specific for channel catfish Ig. A third population, monocytes, was isolated or depleted by adherence to baby hamster kidney cell microexudate-coated surfaces or adherence to Sephadex G-10, respectively. The results indicated that only the T cells were able to respond in the fish MLR, with monocytes being required as accessory cells. In contrast, all three cell types could function as stimulator cells. In addition, it was observed that low in vitro culture temperatures inhibited the generation of channel catfish MLRs, thereby supporting the contention that low temperature immunosuppression in fish results from a preferential inhibition of the generation of primary T-cell responses. PMID:2944817

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

NASA Astrophysics Data System (ADS)

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

2006-02-01

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

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

PubMed Central

Laurence, J; Mitra, D; Steiner, M; Lynch, D H; Siegal, F P; Staiano-Coico, L

1996-01-01

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. PMID:8609222

GENERATION OF CYTOTOXIC LYMPHOCYTES IN MIXED LYMPHOCYTE REACTIONS

PubMed Central

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

Transequatorial Propagation and Depletion Precursors

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-22

Lymphocyte-Rich Classical Hodgkin Lymphoma; Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma; Recurrent Mixed Cellularity Classical Hodgkin Lymphoma; Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma; Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma; Refractory Mixed Cellularity Classical Hodgkin Lymphoma; Refractory Nodular Sclerosis Classical Hodgkin Lymphoma

Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes

PubMed Central

Garnett, C. T.; Erdman, D.; Xu, W.; Gooding, Linda R.

2002-01-01

The common species C adenoviruses (serotypes Ad1, Ad2, Ad5, and Ad6) infect more than 80% of the human population early in life. Following primary infection, the virus can establish an asymptomatic persistent infection in which infectious virions are shed in feces for several years. The probable source of persistent virus is mucosa-associated lymphoid tissue, although the molecular details of persistence or latency of adenovirus are currently unknown. In this study, a sensitive real-time PCR assay was developed to quantitate species C adenovirus DNA in human tissues removed for routine tonsillectomy or adenoidectomy. Using this assay, species C DNA was detected in Ficoll-purified lymphocytes from 33 of 42 tissue specimens tested (79%). The levels varied from fewer than 10 to greater than 2 × 106 copies of the adenovirus genome/107 cells, depending on the donor. DNA from serotypes Ad1, Ad2, and Ad5 was detected, while the rarer serotype Ad6 was not. When analyzed as a function of donor age, the highest levels of adenovirus genomes were found among the youngest donors. Antibody-coated magnetic beads were used to purify lymphocytes into subpopulations and determine whether viral DNA could be enriched within any purified subpopulations. Separation of T cells (CD4/8- expressing and/or CD3-expressing cells) enriched viral DNA in each of nine donors tested. In contrast, B-cell purification (CD19-expressing cells) invariably depleted or eliminated viral DNA. Despite the frequent finding of significant quantities of adenovirus DNA in tonsil and adenoid tissues, infectious virus was rarely present, as measured by coculture with permissive cells. These findings suggest that human mucosal T lymphocytes may harbor species C adenoviruses in a quiescent, perhaps latent form. PMID:12368303

Extracts of chronic lymphocytic leukemia lymphocytes have a high level of DNA repair activity for O/sup 6/-methylguanine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waldstein, E.A.; Cao, E.H.; Miller, M.E.

Extracts of peripheral lymphocytes from six individuals with chronic lymphocytic leukemia (CLL) were assayed for the ability to remove O/sup 6/-methylguanine (O/sup 6/MeGua) from exogenous DNA. The O/sup 6/MeGua-removing activity in CLL lymphocytes, predominantly B cells, was approximately 7-fold higher than in B lymphocytes of normal individuals and about 2-fold higher than in the unstimulated T type cells of normal persons. The activity measured in extracts of lymphocytes from three blood relatives was in the upper range of the normal distribution. Over 80% of the removal of O/sup 6/MeGua was accomplished by the transfer of the methyl group to cysteinemore » moieties of acceptor proteins in a stoichiometric reaction. If one assumes one acceptor group per acceptor protein, the calculated number of acceptor molecules per CLL lymphocyte falls between 91,000 and 220,000. Thus CLL lymphocytes do not show lower O/sup 6/MeGua-removing activity, in contrast to many tumor cell strains or transformed cell lines, which are reported to have a deficient methyl excision repair phenotype (Mer/sup -/). Instead, the CLL lymphocytes act as if they have a super-Mer/sup +/ phenotype.« less

HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE

PubMed Central

Caza, Tiffany N; Fernandez, David R; Talaber, Gergely; Oaks, Zachary; Haas, Mark; Madaio, Michael P; Lai, Zhi-wei; Miklossy, Gabriella; Singh, Ram R; Chudakov, Dmitriy M; Malorni, Walter; Middleton, Frank; Banki, Katalin; Perl, Andras

2014-01-01

Objective Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupus-prone mice. Methods Mitochondria were evaluated in peripheral blood lymphocytes (PBL) of 38 SLE patients and 21 healthy controls and mouse models by flow cytometry, microscopy and western blot. MRL/lpr mice were treated with 125 μg/kg 3-PEHPC or 1 mg/kg rapamycin for 10 weeks, from 4 weeks of age. Disease was monitored by antinuclear antibody (ANA) production, proteinuria, and renal histology. Results Overexpression of HRES-1/Rab4 increased the mitochondrial mass of PBL (1.4-fold; p=0.019) and Jurkat cells (2-fold; p=0.000016) and depleted the mitophagy initiator protein Drp1 both in human (−49%; p=0.01) and mouse lymphocytes (−41%; p=0.03). Drp1 protein levels were profoundly diminished in PBL of SLE patients (−86±3%; p=0.012). T cells of 4-week-old MRL/lpr mice exhibited 4.7-fold over-expression of Rab4A (p=0.0002), the murine homologue of HRES-1/Rab4, and depletion of Drp1 that preceded the accumulation of mitochondria, ANA production and nephritis. 3-PEHPC increased Drp1 (p=0.03) and reduced mitochondrial mass in T cells (p=0.02) and diminished ANA production (p=0.021), proteinuria (p=0.00004), and nephritis scores of lupus-prone mice (p<0.001). Conclusions These data reveal a pathogenic role for HRES-1/Rab4-mediated Drp1 depletion and identify endocytic control of mitophagy as a treatment target in SLE. PMID:23897774

[A multicenter study of correlation between peripheral lymphocyte counts and CD(+)4T cell counts in HIV/AIDS patients].

PubMed

Xie, Jing; Qiu, Zhifeng; Han, Yang; Li, Yanling; Song, Xiaojing; Li, Taisheng

2015-02-01

To evaluate the accuracy of lymphocyte count as a surrogate for CD(+)4T cell count in treatment-naїve HIV-infected adults. A total of 2 013 HIV-infected patients were screened at 23 sites in China. CD(+)4T cell counts were measured by flow cytometry. Correlation between CD(+)4T cell count and peripheral lymphocyte count were analyzed by spearman coefficient. AUCROC were used to evaluate the performance of lymphocyte count as a surrogate for CD(+)4T cell count. The lymphocyte count and CD(+)4T cell count of these 2 013 patients were (1 600 ± 670) × 10(6)/L and (244 ± 148) × 10(6)/L respectively. CD(+)4T cell count were positively correlated with lymphocyte count (r = 0.482, P < 0.000 1). AUCROC of lymphocyte count as a surrogate for CD(+)4T cell counts of <100×10(6)/L, <200×10(6)/L and <350×10(6)/L were 0.790 (95%CI 0.761-0.818, P < 0.000 1), 0.733 (95%CI 0.710-0.755, P < 0.000 1) and 0.732 (95%CI 0.706-0.758, P < 0.000 1) respectively. Lymphocyte count could be considerad as a potential surrogate marker for CD(+)4T cell count in HIV/AIDS patients not having access to T cell subset test by flowcytometry.

Radionuclide labeled lymphocytes for therapeutic use

DOEpatents

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

1985-01-01

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

Radionuclide labeled lymphocytes for therapeutic use

DOEpatents

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

1983-05-03

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

Signaling via the CD2 receptor enhances HTLV-1 replication in T lymphocytes.

PubMed

Guyot, D J; Newbound, G C; Lairmore, M D

1997-07-21

Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of adult T cell leukemia/lymphoma and several chronic progressive immune-mediated diseases. Approximately 1-4% of infected individuals develop disease, generally decades following infection. Increased proviral transcription, mediated by the viral 40-kDa trans-activating protein, Tax, has been implicated in the pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains sequences responsive to cyclic AMP and protein kinase C, we hypothesized that lymphocyte activation signals initiated through the TCR/CD3 complex or CD2 receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate that mAbs directed against the CD2, but not the CD3 receptor increase viral p24 capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an immortalized HTLV-1 cell line. Consistent with transcriptional regulation, reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene construct under control of the HTLV-1 promoter. These data suggest a possible physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte activation may promote viral transcription in infected lymphocytes.

Lenalidomide, Ibrutinib, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma That Is Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-13

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

Effect of 90-day space flight (MDS-ISS) on immunological parameters in mice: lymphocyte distribution and function

NASA Astrophysics Data System (ADS)

Roberts, Arthur; Lhuillier, Andrew; Liu, Yi; Ruggiu, Alessandra; Shi, Yufang

Elucidation of the effects of space flight on the immune system of astronauts and other animal species is important for the survival and success of manned space flight, especially long-term missions. Space flight exposes astronauts to microgravity, galactic cosmic radiation (GCR), and various psycho-social stressors. Blood samples from astronauts returning from space flight have shown changes in the numbers and types of circulating leukocytes. Similarly, normal lym-phocyte homeostasis has been shown to be severely affected in mice using ground-based models of microgravity and GCR exposure, as demonstrated by profound effects on several immuno-logical parameters examined by other investigators and ourselves. In particular, lymphocyte numbers are significantly reduced and subpopulation distribution is altered in the spleen, thy-mus, and peripheral blood following hindlimb unloading (HU) in mice. Lymphocyte depletion was found to be mediated through corticosteroid-induced apoptosis, although the molecular mechanism of apoptosis induction is still under investigation. The proliferative capacity of TCR-stimulated lymphocytes was also inhibited after HU. We have similarly shown that mice exposed to high-energy 56Fe ion radiation have decreased lymphocyte numbers and perturba-tions in proportions of various subpopulations, including CD4+ and CD8+ T cells, and B cells in the spleen, and maturation stages of immature T cells in the thymus. To compare these ground-based results to the effects of actual space-flight, fresh spleen and thymus samples were recently obtained from normal and transgenic mice immediately after 90 d. space-flight in the MDS, and identically-housed ground control mice. Total leukocyte numbers in each organ were enumerated, and subpopulation distribution was examined by flow cytometric analysis of CD3, CD4, CD8, CD19, CD25, DX-5, and CD11b. Splenic T cells were stimulated with anti-CD3 and assessed for proliferation after 2-4 d., and production of

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

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

MedlinePlus

... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Research ... help researchers learn more about how CLL develops. New drugs for chronic lymphocytic leukemia Dozens of new ...

Prognosis of chronic lymphocytic leukemia from infrared spectra of lymphocytes

NASA Astrophysics Data System (ADS)

Schultz, Christian P.; Liu, Kan-Zhi; Johnston, James B.; Mantsch, Henry H.

1997-06-01

Peripheral mononuclear cells obtained from blood of normal individuals and from patients with chronic lymphocytic leukemia (CLL) were investigated by infrared spectroscopy and multivariate statistical analysis. Not only are the spectra of CLL cells different from those of normal cells, but hierarchical clustering also separated the CLL cells into a number of subclusters, based on their different DNA content, a fact which may provide a useful diagnostic tool for staging (progression of the disease) and multiple clone detection. Moreover, there is evidence for a correlation between the increased amount of DNA in the CLL cells and the in-vivo doubling time of the lymphocytes in a given patient.

Differential immunotoxic effects of ethanol on murine EL-4 lymphoma and normal lymphocytes is mediated through increased ROS production and activation of p38MAPK.

PubMed

Premachandran, Sudha; Khan, Nazir M; Thakur, Vikas S; Shukla, Jyoti; Poduval, T B

2012-08-01

Ethanol has been used to achieve thymic depletion in myasthenia gravis patients. Ethanol (95%) has also been used widely in the therapy of many tumors including hepatocellular carcinoma. In light of these findings, we delineated the differential immunotoxic behavior and mechanism of lower concentration of ethanol towards murine EL-4 lymphoma and its normal counterpart lymphocytes. EL-4 lymphoma and normal lymphocytes were cultured with ethanol (0%-5%) for 6 h and cytotoxicity was measured by various methods. EL-4 cells treated with ethanol showed concentration-dependent loss of viability at 2%-5% ethanol concentration and exhibit proliferative arrest at preG1 stage. Acridine-orange and ethidium-bromide staining indicated that ethanol induced death in EL-4 cells, by induction of both apoptosis and necrosis which was further supported by findings of DNA-fragmentation and trypan blue dye exclusion test. However, treatment of lymphocytes with similar concentration of ethanol did not show any death-associated parameters. Furthermore, ethanol induced significantly higher ROS generation in EL-4 cells as compared to lymphocytes and caused PARP cleavage and activation of apoptotic proteins like p53 and Bax, in EL-4 cells and not in normal lymphocytes. In addition, ethanol exposure to EL-4 cells led to phosphorylation of p38MAPK, and upregulation of death receptor Fas (CD95). Taken together, these results suggest that ethanol upto a concentration of 5% caused no significant immunotoxicity towards normal lymphocytes and induced cell death in EL-4 cells via phosphorylation of p38MAPK and regulation of p53 leading to further activation of both extrinsic (Fas) and intrinsic (Bax) apoptotic markers.

Measurement of exercise-induced oxidative stress in lymphocytes.

PubMed

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.

IMMUNOGLOBULIN SPOTS ON THE SURFACE OF RABBIT LYMPHOCYTES

PubMed Central

Pernis, Benvenuto; Forni, Luciana; Amante, Luisa

1970-01-01

Small and medium lymphocytes from the peripheral blood and lymphoid tissues of the rabbit react in suspension with antibodies directed against different immunoglobulin determinants. Through immunofluorescence, it was possible to show that numerous discrete spots on the surface of the positive lymphocytes carry immunoglobulin molecules. The positive lymphocytes are about one-half of all lymphocytes in the different preparations; thymus lymphocytes are all negative. With antisera specific for rabbit IgM as well as with antisera directed against allotypic determinants specific for IgM or IgG, it was possible to show that about nine-tenths of the immunoglobulin-positive lymphocytes carry IgM molecules on their surface. With antisera directed against a- and b-locus determinants, it was also possible to demonstrate that both heavy and light chains were present in the surface immunoglobulins. Furthermore, in animals which were heterozygous at the a or the b locus, it was found that each lymphocyte had immunoglobulins synthesized under the influence of only one of two alleles. A very small proportion of lymphocytes could be shown to have a specific surface reaction with one antigen (horse ferritin); the proportion of these cells increased very much after immunization. PMID:4919141

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

ClinicalTrials.gov

2017-12-05

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

The cytotoxicity of anti-CD22 immunotoxin is enhanced by bryostatin 1 in B-cell lymphomas through CD22 upregulation and PKC-βII depletion.

PubMed

Biberacher, Viola; Decker, Thomas; Oelsner, Madlen; Wagner, Michaela; Bogner, Christian; Schmidt, Burkhard; Kreitman, Robert J; Peschel, Christian; Pastan, Ira; Meyer Zum Büschenfelde, Christian; Ringshausen, Ingo

2012-05-01

In spite of potent first-line therapies for chronic lymphocytic leukemia, treatment remains palliative and all patients frequently relapse. Treatment options for these patients are more limited. BL22 is a recombinant protein composed of the variable region of a monoclonal antibody that binds to CD22 and of PE38, a truncated Pseudomonas exotoxin. BL22 is a very potent drug already used in patients with hairy cell leukemia, whereas in chronic lymphocytic leukemia its cytotoxicity is limited by a lower expression of CD22. Here we demonstrate that this limitation can be overcome by pre-activation of chronic lymphocytic leukemia cells with bryostatin 1. Primary malignant B cells from chronic lymphocytic leukemia and mantle cell lymphoma patients were used in vitro to assess the therapeutic impact of drug combinations using BL22 and bryostatin 1. We demonstrate that bryostatin 1 sensitizes chronic lymphocytic leukemia cells for the cytotoxic effects of BL22 through activation of protein kinase C and subsequently increased CD22 surface expression. Dose and time response analysis reveals that activation of protein kinase C further activates an autocrine feedback loop degrading protein kinase C-βII protein. Depletion of protein kinase C-βII and upregulation of CD22 persist for several days following pre-stimulation with bryostatin 1. Therefore, our data provide a rationale for the sequential administration of BL22 following bryostatin 1 treatment. In addition to primary chronic lymphocytic leukemia cells, bryostatin 1 also sensitizes diffuse large B-cell lymphoma and mantle cell lymphoma cells to BL22 induced apoptosis. Our data suggest that the combination of bryostatin 1 with antibodies directed against CD22 is a potent drug combination for the treatment of low- and high-grade B-cell lymphoma.

The cytotoxicity of anti-CD22 immunotoxin is enhanced by bryostatin 1 in B-cell lymphomas through CD22 upregulation and PKC-βII depletion

PubMed Central

Biberacher, Viola; Decker, Thomas; Oelsner, Madlen; Wagner, Michaela; Bogner, Christian; Schmidt, Burkhard; Kreitman, Robert J.; Peschel, Christian; Pastan, Ira; Meyer zum Büschenfelde, Christian; Ringshausen, Ingo

2012-01-01

Background In spite of potent first-line therapies for chronic lymphocytic leukemia, treatment remains palliative and all patients frequently relapse. Treatment options for these patients are more limited. BL22 is a recombinant protein composed of the variable region of a monoclonal antibody that binds to CD22 and of PE38, a truncated Pseudomonas exotoxin. BL22 is a very potent drug already used in patients with hairy cell leukemia, whereas in chronic lymphocytic leukemia its cytotoxicity is limited by a lower expression of CD22. Here we demonstrate that this limitation can be overcome by pre-activation of chronic lymphocytic leukemia cells with bryostatin 1. Design and Methods Primary malignant B cells from chronic lymphocytic leukemia and mantle cell lymphoma patients were used in vitro to assess the therapeutic impact of drug combinations using BL22 and bryostatin 1. Results We demonstrate that bryostatin 1 sensitizes chronic lymphocytic leukemia cells for the cytotoxic effects of BL22 through activation of protein kinase C and subsequently increased CD22 surface expression. Dose and time response analysis reveals that activation of protein kinase C further activates an autocrine feedback loop degrading protein kinase C-βII protein. Depletion of protein kinase C-βII and upregulation of CD22 persist for several days following pre-stimulation with bryostatin 1. Therefore, our data provide a rationale for the sequential administration of BL22 following bryostatin 1 treatment. In addition to primary chronic lymphocytic leukemia cells, bryostatin 1 also sensitizes diffuse large B-cell lymphoma and mantle cell lymphoma cells to BL22 induced apoptosis. Conclusions Our data suggest that the combination of bryostatin 1 with antibodies directed against CD22 is a potent drug combination for the treatment of low- and high-grade B-cell lymphoma. PMID:22180432

Association of neutrophil-lymphocyte ratio and T lymphocytes with the pathogenesis and progression of HBV-associated primary liver cancer

PubMed Central

Han, Junyan; Wang, Lijia; Li, Mengge; Jiang, Yuyong; Wang, Xianbo; Yang, Zhiyun

2017-01-01

Background The neutrophil–lymphocyte ratio (NLR) is a new prognostic predictor for patients with liver cancer. The association of NLR and T lymphocytes with the pathogenesis and progression of liver cancer is poorly understood. Methods Seventy-three patients with hepatitis B virus (HBV)-associated primary liver cancer (HBV-PLC), 50 patients with HBV-associated liver cirrhosis (HBV-LC) and 37 patients with chronic HBV infection (CHB) were prospectively enrolled from July 1, 2013 to February 28, 2014 in Beijing Ditan Hospital, Capital Medical University (Beijing, China). The NLR, proportions and concentrations of neutrophils and lymphocytes, concentration of subpopulations of lymphocytes, and the expression of CD31 (index for recent thymic output) and HLA-DR (index for activation of T lymphocytes) of T cells in the peripheral blood samples of the patients were assessed and statistically compared between different groups. Results The NLR was significantly increased from patients with CHB, those with HBV-LC to those with HBV-PLC (P<0.05), along with significant increase of neutrophils and decrease of lymphocytes in the same way (P<0.05). The concentrations of T lymphocytes, natural killer cells, B cells, CD4+ T cells and CD8+ T cells were decreased from patients with CHB, those with HBV-LC to those with HBV-PLC, and were significantly reduced in patients with HBV-PLC compared with those in patients with CHB (P<0.05). The CD31 and HLA-DR expression of naive CD4+ and CD8+ T cells was significantly decreased and increased, respectively in patients with HBV-PLC compared with that in patients with CHB. Conclusions Elevated NLR, resulted from the increase of neutrophils and decrease of lymphocytes, is positively associated with the pathogenesis and progression of HBV-PLC. The reduced thymic output and hyperactivation of T lymphocytes may contribute to the decrease of T lymphocytes, which could be also related to the pathogenesis of HBV-PLC. PMID:28231294

Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial

PubMed Central

Francois, Bruno; Daix, Thomas; Walton, Andrew H.; Shotwell, Matthew S.; Unsinger, Jacqueline; Rimmelé, Thomas; Blood, Teresa; Morre, Michel; Gregoire, Anne; Mayo, Gail A.; Blood, Jane; Durum, Scott K.; Hotchkiss, Richard S.

2018-01-01

BACKGROUND. A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS. We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 weeks. Primary aims were to determine the safety of CYT107 in sepsis and its ability to reverse lymphopenia. RESULTS. CYT107 was well tolerated without evidence of inducing cytokine storm or worsening inflammation or organ dysfunction. CYT107 caused a 3- to 4-fold increase in absolute lymphocyte counts and in circulating CD4+ and CD8+ T cells that persisted for weeks after drug administration. CYT107 also increased T cell proliferation and activation. CONCLUSIONS. This is the first trial of an immunoadjuvant therapy targeting defects in adaptive immunity in patients with sepsis. CYT107 reversed the marked loss of CD4+ and CD8+ immune effector cells, a hallmark of sepsis and a likely key mechanism in its morbidity and mortality. CYT107 represents a potential new way forward in the treatment of patients with sepsis by restoring adaptive immunity. Such immune-based therapy should be broadly protective against diverse pathogens including multidrug resistant bacteria that preferentially target patients with impaired immunity. TRIAL REGISTRATION. Trials registered at clinicaltrials.gov: NCT02640807 and NCT02797431. FUNDING. Revimmune, NIH National Institute of General Medical Sciences GM44118. PMID:29515037

T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.

PubMed

Vago, Luca; Oliveira, Giacomo; Bondanza, Attilio; Noviello, Maddalena; Soldati, Corrado; Ghio, Domenico; Brigida, Immacolata; Greco, Raffaella; Lupo Stanghellini, Maria Teresa; Peccatori, Jacopo; Fracchia, Sergio; Del Fiacco, Matteo; Traversari, Catia; Aiuti, Alessandro; Del Maschio, Alessandro; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara

2012-08-30

The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

Ego depletion impairs implicit learning.

PubMed

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

2014-01-01

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

Ego Depletion Impairs Implicit Learning

PubMed Central

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

2014-01-01

Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent. PMID:25275517

Exposure to nature counteracts aggression after depletion.

PubMed

Wang, Yan; She, Yihan; Colarelli, Stephen M; Fang, Yuan; Meng, Hui; Chen, Qiuju; Zhang, Xin; Zhu, Hongwei

2018-01-01

Acts of self-control are more likely to fail after previous exertion of self-control, known as the ego depletion effect. Research has shown that depleted participants behave more aggressively than non-depleted participants, especially after being provoked. Although exposure to nature (e.g., a walk in the park) has been predicted to replenish resources common to executive functioning and self-control, the extent to which exposure to nature may counteract the depletion effect on aggression has yet to be determined. The present study investigated the effects of exposure to nature on aggression following depletion. Aggression was measured by the intensity of noise blasts participants delivered to an ostensible opponent in a competition reaction-time task. As predicted, an interaction occurred between depletion and environmental manipulations for provoked aggression. Specifically, depleted participants behaved more aggressively in response to provocation than non-depleted participants in the urban condition. However, provoked aggression did not differ between depleted and non-depleted participants in the natural condition. Moreover, within the depletion condition, participants in the natural condition had lower levels of provoked aggression than participants in the urban condition. This study suggests that a brief period of nature exposure may restore self-control and help depleted people regain control over aggressive urges. © 2017 Wiley Periodicals, Inc.

The effect of acute tyrosine phenylalanine depletion on emotion-based decision-making in healthy adults.

PubMed

Vrshek-Schallhorn, Suzanne; Wahlstrom, Dustin; White, Tonya; Luciana, Monica

2013-04-01

Despite interest in dopamine's role in emotion-based decision-making, few reports of the effects of dopamine manipulations are available in this area in humans. This study investigates dopamine's role in emotion-based decision-making through a common measure of this construct, the Iowa Gambling Task (IGT), using Acute Tyrosine Phenylalanine Depletion (ATPD). In a between-subjects design, 40 healthy adults were randomized to receive either an ATPD beverage or a balanced amino acid beverage (a control) prior to completing the IGT, as well as pre- and post-manipulation blood draws for the neurohormone prolactin. Together with conventional IGT performance metrics, choice selections and response latencies were examined separately for good and bad choices before and after several key punishment events. Changes in response latencies were also used to predict total task performance. Prolactin levels increased significantly in the ATPD group but not in the control group. However, no significant group differences in performance metrics were detected, nor were there sex differences in outcome measures. However, the balanced group's bad deck latencies speeded up across the task, while the ATPD group's latencies remained adaptively hesitant. Additionally, modulation of latencies to the bad decks predicted total score for the ATPD group only. One interpretation is that ATPD subtly attenuated reward salience and altered the approach by which individuals achieved successful performance, without resulting in frank group differences in task performance. Copyright © 2013 Elsevier Inc. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

THE MECHANISM OF ACTION OF ANTI-LYMPHOCYTE SERUM

PubMed Central

Lance, Eugene M.

1969-01-01

Studies designed to gain insight into the mechanism of action of the active component of antilymphocyte serum were carried out using an antibody eluate prepared from the IgG fraction of anti-lymphocyte serum by absorption and subsequent elution from thymocyte membrane. The resulting antibody eluate was labeled with radionuclide tracer to determine the fate of the antibody in vivo. The result indicated that anti-lymphocytic antibodies are eliminated from recipients extremely rapidly. The mechanism for this rapid clearance appears to depend upon the absorption of antibody molecules onto lymphocyte surfaces and the subsequent clearing and degradation of the antibody-lymphocyte complexes by the reticuloendothelial system. Distribution studies confirm that the major site of antibody-lymphocyte interaction occurs in the periphery with relatively little penetration of antibody within lymphoid organs. Radioautographic studies showed that the pattern of localization within lymphoid and other organs is confined to rather specific areas. These observations are believed to offer strong support for the notion that anti-lymphocyte serum achieves its immunosuppressive effect by bringing about a selective ablation of the population of recirculating lymphocytes. PMID:4183778

Response of lymphocytes to a mitogenic stimulus during spaceflight

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1989-01-01

Several studies were performed that demonstrate that immunological activities of lymphocytes can be affected by spaceflight or by models that attempt to simulate some aspects of weightlessness. Included among these are the responses of lymphocytes to external stimuli such as mitogens and viruses. When cultures of lymphocytes were flown in space, the ability of the lymphocytes to respond to mitogens was inhibited. Similar results were obtained when lymphocytes from astronauts or animals just returned from space were placed into culture immediately upon return to earth, and when models of hypogravity were used. Lymphocytes placed in culture during spaceflights produced enhanced levels of interferon compared to control cultures. When cultures of lymphocytes were prepared for cosmonauts or rodents immediately upon return to earth, interferon production was inhibited. These results suggest that space flight can have profound effects on lymphocyte function, and that effects on isolated cells may be different from that on cells in the whole organism.

Effect of rituximab on human in vivo antibody immune responses.

PubMed

Pescovitz, Mark D; Torgerson, Troy R; Ochs, Hans D; Ocheltree, Elizabeth; McGee, Paula; Krause-Steinrauf, Heidi; Lachin, John M; Canniff, Jennifer; Greenbaum, Carla; Herold, Kevan C; Skyler, Jay S; Weinberg, Adriana

2011-12-01

B-lymphocyte depletion with rituximab has been shown to benefit patients with various autoimmune diseases. We have previously demonstrated that this benefit is also apparent in patients with newly diagnosed type 1 diabetes. The effect of rituximab on in vivo antibody responses, particularly during the period of B-lymphocyte depletion, is incompletely determined. This study was designed to assess this knowledge void. In patients with recent-onset type 1 diabetes treated with rituximab (n = 46) or placebo (n = 29), antibody responses to neoantigen phiX174 during B-lymphocyte depletion and with hepatitis A (as a second neoantigen) and tetanus/diphtheria (as recall antigens) after B-lymphocyte recovery were studied. Anti- tetanus, diphtheria, mumps, measles, and rubella titers were measured before and after treatment by means of ELISA. Antibody titers and percentage IgM versus percentage IgG to phiX174 were measured by means of phage neutralization. B-lymphocyte subsets were determined by means of flow cytometry. No change occurred in preexisting antibody titers. Tetanus/diphtheria and hepatitis A immunization responses were protective in the rituximab-treated subjects, although significantly blunted compared with those seen in the controls subjects, when immunized at the time of B-lymphocyte recovery. Anti-phiX174 responses were severely reduced during the period of B-lymphocyte depletion, but with B-lymphocyte recovery, anti-phiX174 responses were within the normal range. During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights

[The lymphocyte transformation test in dermatology].

PubMed

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.

Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.

PubMed

Chari, D M; Huang, W L; Blakemore, W F

2003-09-15

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs. Copyright 2003 Wiley-Liss, Inc.

Lymphocytic mastopathy mimicking breast malignancy: a case report*

PubMed Central

Campos, Gabriela Couto Possati; Castro, Melissa Vieira Koch e; de Mattos, Viviane Ferreira Esteves; Pinto, Laura Zaiden Ferreira e; Boechat, Marcia Cristina Bastos; dos Santos, Alair Augusto Sarmet Moreira Damas

2014-01-01

Lymphocytic mastopathy affects both young and middle-aged women and is frequently associated with autoimmune diseases. Diagnosis is done by associating clinical (breast tissue thickening or hardened breast lump), radiological (increased breast density, presence of mass and calcifications), sonographic (nodule with posterior acoustic shadowing), histopathological (fibrosis and lymphocytic infiltrate) and immunohistochemical findings. Lymphocytic mastopathy is a benign entity that may mimic carcinoma. The authors report the case of a patient with lymphocytic mastopathy. PMID:25741094

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

PubMed

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

2018-05-01

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

[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].

PubMed

Xie, J; Wang, H L; Qiu, Z F; Li, T S

2016-06-01

To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as

Differentiation Capacity of Cultured B Lymphocytes from Immunodeficient Patients

PubMed Central

Wu, L. Y. F.; Lawton, A. R.; Cooper, M. D.

1973-01-01

Peripheral blood lymphocytes from 27 healthy individuals and from 18 patients with a diverse spectrum of defects in humoral immunity were examined for their capacity to undergo terminal differentiation in vitro. Pokeweed mitogen induced cells from normal persons to synthesize and secrete IgM. IgG, and IgA as detected by Immunofluorescence and incorporation of [14C]amino acids, Lymphocytes from three boys with X-linked agammaglobulinemia were stimulated to proliferate, but did not synthesize immunoglobulin. Lymphocyte cultures from three of four patients having agammaglobulinemia with B lymphocytes produced different immunoglobulin classes in ratios similar to the in vivo distribution of classes of B lymphocytes, Lymphocytes from a dysgammaglobulinemic boy deficient in serum IgG and IgA, but who had normal numbers of IgM-, IgG-, and IgA-bearing B lymphocytes, could not be stimulated by pokeweed mitogen to make IgG and IgA. Synthesis and secretion of IgA, as well as IgM and IgG, was detected in cell cultures from each of 10 patients with isolated IgA deficiency. The results suggest that deficiencies in immunoglobulin synthesis may reflect either (a) failure to develop B lymphocytes, (b) arrested development of B lymphocytes due to intrinsic metabolic abnormalities, or (c) disturbance of factors extrinsic to the B lymphocyte which are essential for normal induction of plasma cell maturation. Images PMID:4543023

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

ClinicalTrials.gov

2018-03-26

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

Neutrophil-lymphocyte ratio in patients with pesticide poisoning.

PubMed

Dundar, Zerrin Defne; Ergin, Mehmet; Koylu, Ramazan; Ozer, Rasit; Cander, Basar; Gunaydin, Yahya Kemal

2014-09-01

Pesticides are highly toxic to human beings, and pesticide poisoning is associated with high morbidity and mortality. The identification of powerful prognostic markers is important for the management of patients with pesticide poisoning in emergency settings. To investigate the prognostic value of the neutrophil-lymphocyte ratio and hematological parameters measured in patients with pesticide poisoning within the first 24 h after admission to the emergency department (ED). All patients (≥15 years old) admitted to the ED from July 2008 through February 2013 due to pesticide poisoning were enrolled in the study. The written and electronic medical charts of patients were reviewed. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated for each patient using absolute neutrophil, lymphocyte, and platelet counts. Mechanical ventilation requirement and mortality were used as the primary endpoints. A total of 189 patients were included in the study. The mechanically ventilated patients had significantly higher leukocyte and neutrophil counts, and neutrophil-lymphocyte and platelet-lymphocyte ratios (p < 0.001, p < 0.001, p < 0.001, p = 0.003, respectively), whereas they had significantly lower lymphocyte counts compared to nonventilated patients (p = 0.011). Survivors had significantly higher leukocyte and neutrophil counts, and neutrophil-lymphocyte ratios (p < 0.001, p < 0.001, p = 0.002, respectively), whereas there was no significant difference between groups in terms of lymphocyte counts (p = 0.463), compared to nonsurvivors. Leukocyte counts, neutrophil counts, and neutrophil-lymphocyte ratios measured within the first 24 h after admission to the ED are useful and easy-to-use parameters for estimating prognosis in the follow-up of patients with pesticide poisoning. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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 (p<0.05). When smokers 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 (p<0.05). Neutrophil/lymphocyte ratio increases in correlation with pack/year while platelet/lymphocyte ratio is not affected 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.

Localization of antigen-specific lymphocytes following lymph node challenge.

PubMed Central

Liu, H; Splitter, G A

1986-01-01

The effect of subcutaneous injections of Brucella abortus strain 19 antigen on the specific localization of autologous lymphocytes in the regional nodes of calves was analysed by fluorescent labelling and flow cytometry. Both in vitro and in vivo FITC labelling of lymphocytes indicated the preferential migration of lymphocytes from a previously challenged lymph node to a recently challenged lymph node. However, lymphocytes from a lymph node challenged with B. abortus failed to localize preferentially in a lymph node challenged with a control antigen, Listeria monocytogenes. Lymph node cells, enriched for T lymphocytes and isolated from primary stimulated or secondary challenged B. abortus lymph nodes, could proliferate when cultured with autologous antigen-pulsed macrophages. The kinetics of [3H]thymidine incorporation in lymphocytes from secondarily challenged lymph nodes occurred earlier and to a greater extent when compared with lymphocytes from primary challenged lymph nodes. Our data show that the accumulation of B. abortus-specific lymphocytes in secondarily challenged lymph nodes is increased by the presence of the specific antigen. Images Figure 4 PMID:2426183

Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes.

PubMed

Moritoyo, T; Reinhart, T A; Moritoyo, H; Sato, E; Izumo, S; Osame, M; Haase, A T

1996-07-01

Infection by human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia and a slowly progressive disease of the central nervous system (CNS), HTLV-I-associated myelopathy/tropical spastic paraparesis, characterized pathologically by inflammation and white matter degeneration in the spinal cord. One of the explanations for the tissue destruction is that HTLV-I infects cells in the CNS, or HTLV-I-infected CD4+ T lymphocytes enter the CNS, and this drives local expansion of virus-specific CD8+ cytotoxic T lymphocytes, which along with cytokines cause the pathological changes. Because both in the circulation and in the cerebrospinal fluid, CD8+ cytotoxic T lymphocytes are primarily reactive to the product of the HTLV-I tax gene, we sought evidence of expression of this gene within cells in the inflammatory lesions. After using double-label in situ hybridization techniques, we now report definitive localization of HTLV-I tax gene expression in CD4+ T lymphocytes in areas of inflammation and white matter destruction. These findings lend support to a hypothetical scheme of neuropathogenesis in which HTLV-I tax gene expression provokes and sustains an immunopathological process that progressively destroys myelin and axons in the spinal cord.

Elevated numbers of CD163+ macrophages in hearts of simian immunodeficiency virus-infected monkeys correlate with cardiac pathology and fibrosis.

PubMed

Walker, Joshua A; Sulciner, Megan L; Nowicki, Katherine D; Miller, Andrew D; Burdo, Tricia H; Williams, Kenneth C

2014-07-01

The role of macrophage activation, traffic, and accumulation on cardiac pathology was examined in 23 animals. Seventeen animals were simian immunodeficiency virus (SIV) infected, 12 were CD8 lymphocyte depleted, and the remaining six were uninfected controls (two CD8 lymphocyte depleted, four nondepleted). None of the uninfected controls had cardiac pathology. One of five (20%) SIV-infected, non-CD8 lymphocyte-depleted animals had minor cardiac pathology with increased numbers of macrophages in ventricular tissue compared to controls. Seven of the 12 (58%) SIV-infected, CD8 lymphocyte-depleted animals had cardiac pathology in ventricular tissues, including macrophage infiltration and myocardial degeneration. The extent of fibrosis (measured as the percentage of collagen per tissue area) was increased 41% in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to animals without pathological abnormalities. The number of CD163+ macrophages increased significantly in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to ones without pathology (1.66-fold) and controls (5.42-fold). The percent of collagen (percentage of collagen per total tissue area) positively correlated with macrophage numbers in ventricular tissue in SIV-infected animals. There was an increase of BrdU+ monocytes in the heart during late SIV infection, regardless of pathology. These data implicate monocyte/macrophage activation and accumulation in the development of cardiac pathology with SIV infection.

Alzheimer's lymphocytes are resistant to ultraviolet B-induced apoptosis.

PubMed

Zana, Marianna; Juhász, Anna; Rimanóczy, Agnes; Bjelik, Annamária; Baltás, Eszter; Ocsovszki, Imre; Boda, Krisztina; Penke, Botond; Dobozy, Attila; Kemény, Lajos; Janka, Zoltán; Kálmán, János

2006-06-01

In the present pilot investigation, the susceptibility of T-lymphocytes from Alzheimer's disease (AD) subjects (n=22) and aged-matched, non-demented controls (CNT) (n=12) was examined with ultraviolet (UV) B light-induced apoptosis in vitro. The basal apoptotic ratios were similar in both groups. However, the AD lymphocytes displayed significantly (p<0.0001) lower apoptotic levels than those of the CNT lymphocytes at all of the applied UVB exposure doses (100, 200 and 300 mJ/cm(2)). These observations indicate that AD lymphocytes are more resistant than CNT lymphocytes to UVB irradiation.

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior.

PubMed

Sun, Dong; Sun, Xiang-Dong; Zhao, Lu; Lee, Dae-Hoon; Hu, Jin-Xia; Tang, Fu-Lei; Pan, Jin-Xiu; Mei, Lin; Zhu, Xiao-Juan; Xiong, Wen-Cheng

2018-01-08

Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.

Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

PubMed

Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

2016-07-01

The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01-8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23-24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15-8.85) was associated significantly with progression-free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18-10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression-free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the

Too Depleted to Try? Testing the Process Model of Ego Depletion in the Context of Unhealthy Snack Consumption.

PubMed

Haynes, Ashleigh; Kemps, Eva; Moffitt, Robyn

2016-11-01

The process model proposes that the ego depletion effect is due to (a) an increase in motivation toward indulgence, and (b) a decrease in motivation to control behaviour following an initial act of self-control. In contrast, the reflective-impulsive model predicts that ego depletion results in behaviour that is more consistent with desires, and less consistent with motivations, rather than influencing the strength of desires and motivations. The current study sought to test these alternative accounts of the relationships between ego depletion, motivation, desire, and self-control. One hundred and fifty-six undergraduate women were randomised to complete a depleting e-crossing task or a non-depleting task, followed by a lab-based measure of snack intake, and self-report measures of motivation and desire strength. In partial support of the process model, ego depletion was related to higher intake, but only indirectly via the influence of lowered motivation. Motivation was more strongly predictive of intake for those in the non-depletion condition, providing partial support for the reflective-impulsive model. Ego depletion did not affect desire, nor did depletion moderate the effect of desire on intake, indicating that desire may be an appropriate target for reducing unhealthy behaviour across situations where self-control resources vary. © 2016 The International Association of Applied Psychology.

Donor CTLA-4 genotype influences clinical outcome after T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA-identical sibling donors.

PubMed

Bosch-Vizcaya, Anna; Pérez-García, Arianne; Brunet, Salut; Solano, Carlos; Buño, Ismael; Guillem, Vicent; Martínez-Laperche, Carolina; Sanz, Guillermo; Barrenetxea, Cristina; Martínez, Carmen; Tuset, Esperanza; Lloveras, Natàlia; Coll, Rosa; Guardia, Ramon; González, Yolanda; Roncero, Josep M; Bustins, Anna; Gardella, Santiago; Fernández, Cristalina; Buch, Joan; Gallardo, David

2012-01-01

CTLA-4 (cytotoxic T-lymphocyte antigen-4) plays a pivotal role in inhibiting T cell activation through competitive interaction with B7 molecules and interruption of costimulatory signals mediated by CD28. Polymorphisms on the CTLA-4 gene have been previously associated with autoimmune diseases, predisposition to leukemic relapse, and with graft-versus-host disease (GVHD) or relapse after allogeneic transplant. As CTLA-4 is expressed on T-lymphocytes, the aim of this study was to determine whether the donor CTLA-4 CT60 genotype also influences clinical outcome even after T cell depletion with CD34-positive selection. We studied 136 patient-donor pairs. Overall survival (OS) was worse for those patients who received grafts from a donor with the CT60 AA genotype rather than from a donor with the AG or GG genotype (35.6% vs 49.4%; P = .043). This association was confirmed through multivariate analysis, which identified the donor CT60 genotype as an independent risk factor for OS (P = .008; hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.23-4.08). The donor CT60 AA genotype was also associated with lower disease-free survival, this being related to an increased risk of relapse (P = .001; HR: 3.41, 95% CI: 1.67-6.96) and a trend toward higher transplant-related mortality. These associations were stronger when considering only patients in the early stage of disease. Our results suggest that graft-versus-leukemia (GVL) activity after T cell depletion is conditioned by the donor CTLA-4 genotype. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review.

PubMed

Jawad, Hadeel; McCarthy, Peter; O'Leary, Gerard; Heffron, Cynthia C

2018-05-01

Warthin tumor is the second most common salivary gland neoplasm. It occurs more commonly in males than in females. Malignant transformation in Warthin tumor is a rare but well-recognized phenomenon; however, the development or presentation of lymphoma in a Warthin tumor is rare. An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular lymph nodes. The histological diagnosis was malignant lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, present within the stroma of a Warthin tumor, and also present within the adjacent lymph node. This case is the third reported case describing a collision of Warthin tumor and chronic lymphocytic leukemia/small lymphocytic lymphoma. It also emphasizes the importance of careful examination of the lymphoid stroma of these tumors.

Endothelial Depletion of Acvrl1 in Mice Leads to Arteriovenous Malformations Associated with Reduced Endoglin Expression

PubMed Central

Allinson, Kathleen R.; Redgrave, Rachael E.; Zhai, Zhenhua; Oh, S. Paul; Fruttiger, Marcus; Arthur, Helen M.

2014-01-01

Rare inherited cardiovascular diseases are frequently caused by mutations in genes that are essential for the formation and/or function of the cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease of this type. The majority of patients carry mutations in either Endoglin (ENG) or ACVRL1 (also known as ALK1) genes, and the disease is characterized by arteriovenous malformations and persistent haemorrhage. ENG and ACVRL1 encode receptors for the TGFβ superfamily of ligands, that are essential for angiogenesis in early development but their roles are not fully understood. Our goal was to examine the role of Acvrl1 in vascular endothelial cells during vascular development and to determine whether loss of endothelial Acvrl1 leads to arteriovenous malformations. Acvrl1 was depleted in endothelial cells either in early postnatal life or in adult mice. Using the neonatal retinal plexus to examine angiogenesis, we observed that loss of endothelial Acvrl1 led to venous enlargement, vascular hyperbranching and arteriovenous malformations. These phenotypes were associated with loss of arterial Jag1 expression, decreased pSmad1/5/8 activity and increased endothelial cell proliferation. We found that Endoglin was markedly down-regulated in Acvrl1-depleted ECs showing endoglin expression to be downstream of Acvrl1 signalling in vivo. Endothelial-specific depletion of Acvrl1 in pups also led to pulmonary haemorrhage, but in adult mice resulted in caecal haemorrhage and fatal anaemia. We conclude that during development, endothelial Acvrl1 plays an essential role to regulate endothelial cell proliferation and arterial identity during angiogenesis, whilst in adult life endothelial Acvrl1 is required to maintain vascular integrity. PMID:24896812

Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease)

PubMed Central

Sergi, Consolato; Shen, Fan; Bouma, Gerd

2017-01-01

The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy (GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinico-pathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences “across oceans” among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21st century. PMID:28216964

Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

PubMed

Workman, Joanna L; Weber, Michael D; Nelson, Randy J

2011-09-30

Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

[Celiac crisis with quadriplegia due to potassium depletion as presenting feature of celiac disease].

PubMed

Atikou, A; Rabhi, M; Hidani, H; El Alaoui Faris, M; Toloune, F

2009-06-01

Adult coeliac disease revealed by coeliac crisis and quadriplegia due to potassium depletion is an extremely rare situation. A 26-year-old woman presented with a suddenly developed weakness of all four limbs and a severe diarrhea. Authors emphasize coeliac crisis, which is a presenting feature of coeliac disease, characterized by acute diarrhea with life-threatening acid base and electrolyte abnormalities. The patient improved with correction of hypokalemia and gluten-free diet. A severe acute diarrhea with metabolic and systemic complications, the so-called coeliac crisis, is a possible presenting clinical feature of a previously undiagnosed adult celiac disease.

Hypertrophic gastropathy with gastric adenocarcinoma: Menetrier's disease and lymphocytic gastritis?

PubMed Central

Mosnier, J F; Flejou, J F; Amouyal, G; Gayet, B; Molas, G; Henin, D; Potet, F

1991-01-01

Lymphocytic gastritis is a form of gastric inflammation characterised by a pronounced increase in lymphocytes in gastric surface and foveolar epithelium. Lymphocytic gastritis is often associated with endoscopic evidence of 'varioliform gastritis'. Lymphocytic gastritis has recently been reported to be associated with other forms of hypertrophic gastropathies. We present a case of hypertrophic gastropathy with gastric adenocarcinoma, with both Menetrier's disease and lymphocyte gastritis. Immunohistochemical studies showed that the intraepithelial lymphocytes were predominantly alpha/beta T cells as in the normal stomach and not gamma/delta T cells as in coeliac sprue. This case together with the six recently published cases suggests that Menetrier's disease and lymphocytic gastritis may be part of the same disease spectrum. Images Figure 1 Figure 2 PMID:1773969

Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

PubMed

Grau-Roma, Llorenç; Peckham, Robert; Paton, Jacqui; Stahel, Anina; de Brot, Simone

2017-01-01

The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.

Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes.

PubMed

Webb, Matthew W; Sun, Jianping; Sheard, Michael A; Liu, Wei-Yao; Wu, Hong-Wei; Jackson, Jeremy R; Malvar, Jemily; Sposto, Richard; Daniel, Dylan; Seeger, Robert C

2018-04-17

Tumor-associated macrophages can promote growth of cancers. In neuroblastoma, tumor-associated macrophages have greater frequency in metastatic versus loco-regional tumors, and higher expression of genes associated with macrophages helps to predict poor prognosis in the 60% of high-risk patients who have MYCN-non-amplified disease. The contribution of cytotoxic T-lymphocytes to anti-neuroblastoma immune responses may be limited by low MHC class I expression and low exonic mutation frequency. Therefore, we modelled human neuroblastoma in T-cell deficient mice to examine whether depletion of monocytes/macrophages from the neuroblastoma microenvironment by blockade of CSF-1R can improve the response to chemotherapy. In vitro, CSF-1 was released by neuroblastoma cells, and topotecan increased this release. In vivo, neuroblastomas formed by subcutaneous co-injection of human neuroblastoma cells and human monocytes into immunodeficient NOD/SCID mice had fewer human CD14 + and CD163 + cells and mouse F4/80 + cells after CSF-1R blockade. In subcutaneous or intra-renal models in immunodeficient NSG or NOD/SCID mice, CSF-1R blockade alone did not affect tumor growth or mouse survival. However, when combined with cyclophosphamide plus topotecan, the CSF-1R inhibitor BLZ945, either without or with anti-human and anti-mouse CSF-1 mAbs, inhibited neuroblastoma growth and synergistically improved mouse survival. These findings indicate that depletion of tumor-associated macrophages from neuroblastomas can be associated with increased chemotherapeutic efficacy without requiring a contribution from T-lymphocytes, suggesting the possibility that combination of CSF-1R blockade with chemotherapy might be effective in patients who have limited anti-tumor T-cell responses. © 2018 UICC.

Depletion of CD52-positive cells inhibits the development of central nervous system autoimmune disease, but deletes an immune-tolerance promoting CD8 T-cell population. Implications for secondary autoimmunity of alemtuzumab in multiple sclerosis.

PubMed

von Kutzleben, Stephanie; Pryce, Gareth; Giovannoni, Gavin; Baker, David

2017-04-01

The objective was to determine whether CD52 lymphocyte depletion can act to promote immunological tolerance induction by way of intravenous antigen administration such that it could be used to either improve efficiency of multiple sclerosis (MS) inhibition or inhibit secondary autoimmunities that may occur following alemtuzumab use in MS. Relapsing experimental autoimmune encephalomyelitis was induced in ABH mice and immune cell depletion was therapeutically applied using mouse CD52 or CD4 (in conjunction with CD8 or CD20) depleting monoclonal antibodies. Immunological unresponsiveness was then subsequently induced using intravenous central nervous system antigens and responses were assessed clinically. A dose-response of CD4 monoclonal antibody depletion indicated that the 60-70% functional CD4 T-cell depletion achieved in perceived failed trials in MS was perhaps too low to even stop disease in animals. However, more marked (~75-90%) physical depletion of CD4 T cells by CD4 and CD52 depleting antibodies inhibited relapsing disease. Surprisingly, in contrast to CD4 depletion, CD52 depletion blocked robust immunological unresponsiveness through a mechanism involving CD8 T cells. Although efficacy was related to the level of CD4 T-cell depletion, the observations that CD52 depletion of CD19 B cells was less marked in lymphoid organs than in the blood provides a rationale for the rapid B-cell hyper-repopulation that occurs following alemtuzumab administration in MS. That B cells repopulate in the relative absence of T-cell regulatory mechanisms that promote immune tolerance may account for the secondary B-cell autoimmunities, which occur following alemtuzumab treatment of MS. © 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.

Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis.

PubMed

Brix, Silke R; Noriega, Mercedes; Herden, Elisabeth M; Goldmann, Birgit; Langbehn, Ulrike; Busch, Martin; Jabs, Wolfram J; Steinmetz, Oliver M; Panzer, Ulf; Huber, Tobias B; Stahl, Rolf A K; Wiech, Thorsten

2018-06-01

Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. The aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA-associated glomerulonephritis (GN). We investigated 112 renal biopsies from patients with newly diagnosed ANCA-associated necrotising GN. We identified four different levels of the intrarenal organisation of lymphocytes: T cells without B cells, scattered B and T cells, clustered lymphocytic infiltrates and nodular compartmentally arranged B and T cell aggregates. Almost half the patients showed clusters of B and T lymphocytes in their biopsies. In 15 of these biopsies, a higher degree of organisation with lymphocytic compartments was detected. Inflammatory cell organisation was associated with renal failure, but not with tubular atrophy and interstitial fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had worse renal function during follow-up and were more likely to develop end stage renal disease. In the present study, we show that the renal lymphocytic organisation is associated with renal outcome in ANCA-associated GN. The organisation of the lymphocytic infiltrate may be a morphological correlate of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying the lymphocytic infiltrate could help to predict renal outcome, and might therefore be used for individualised adjustments in the intensity and duration of immunosuppressive therapy. © 2018 John Wiley & Sons Ltd.

Examination of the health status of populations from depleted-uranium-contaminated regions.

PubMed

Milacić, Snezana; Petrović, Dragana; Jovicić, Dubravka; Kovacević, Radomir; Simić, Jadranko

2004-05-01

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahrenhoerster, Lori S.; Tate, Everett R.; Lakatos, Peter A.

The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to completemore » lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life.« less

Adult Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Hodgkin lymphoma treatment depends on the type (classical or nodular lymphocyte predominant) and includes chemotherapy and/or radiation therapy. Get comprehensive information on newly diagnosed and recurrent Hodgkin lymphoma treatment in this summary for clinicians.

Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

PubMed Central

Ezzell, Erin E.; Renshaw, John S.

2017-01-01

Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of non-Hodgkin's lymphoma (NHL) in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT) mass resulting in rapid airway compromise. PMID:28396813

Lymphocyte receptors for pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1990-12-01

We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, andmore » 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.« less

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

PubMed

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

2013-04-15

Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function. Copyright © 2013 Elsevier B.V. All rights reserved.

Neural Differentiation in HDAC1-Depleted Cells Is Accompanied by Coilin Downregulation and the Accumulation of Cajal Bodies in Nucleoli.

PubMed

Krejčí, Jana; Legartová, Soňa; Bártová, Eva

2017-01-01

Cajal bodies (CBs) are important compartments containing accumulated proteins that preferentially regulate RNA-related nuclear events, including splicing. Here, we studied the nuclear distribution pattern of CBs in neurogenesis. In adult brains, coilin was present at a high density, but CB formation was absent in the nuclei of the choroid plexus of the lateral ventricles. Cells of the adult hippocampus were characterized by a crescent-like morphology of coilin protein. We additionally observed a 70 kDa splice variant of coilin in adult mouse brains, which was different to embryonic brains and mouse pluripotent embryonic stem cells (mESCs), characterized by the 80 kDa standard variant of coilin. Here, we also showed that depletion of coilin is induced during neural differentiation and HDAC1 deficiency in mESCs caused coilin accumulation inside the fibrillarin-positive region of the nucleoli. A similar distribution pattern was observed in adult brain hippocampi, characterized by lower levels of both coilin and HDAC1. In summary, we observed that neural differentiation and HDAC1 deficiency lead to coilin depletion and coilin accumulation in body-like structures inside the nucleoli.

Preparative electrophoresis of living lymphocytes

NASA Technical Reports Server (NTRS)

Vanoss, C. J.; Bigazzi, P. E.; Gillman, C. F.; Allen, R. E.

1974-01-01

Vertical liquid columns containing low molecular weight dextran density gradients can be used for preparative lymphocyte electrophoresis on earth, in simulation of 0 gravity conditions. Another method that has been tested at 1 G, is the electrophoresis of lymphocytes in a upward direction in vertical columns. By both methods up to 10 to the 7th power lymphocytes can be separated at one time in a 30 cm glass column of 8 mm inside diameter, at 12 v/cm, in 2 hours. Due to convection and sedimentation problems, the separation at 1 G is less than ideal, but it is expected that at 0 gravity electrophoresis will prove to be a uniquely powerful cell separation tool. The technical feasibility of electrophoresing inert particles at 0 G has been proven earlier, during the flight of Apollo 16.

Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.

PubMed

Schröder, H; Heimers, A; Frentzel-Beyme, R; Schott, A; Hoffmann, W

2003-01-01

Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control.

Phenotype study with monoclonal antibodies of T lymphocyte colonies in normal individuals and in patients with chronic OKT8+ lymphocytic leukaemia.

PubMed Central

Andre, C; Farcet, J P; Oudhriri, N; Gourdin, M F; Bouguet, J; Reyes, F

1983-01-01

The lymphocyte colony forming capacity of peripheral blood mononuclear cells from normal controls and from two patients with chronic OKT8+ lymphocytic leukaemia was determined in agar culture under PHA stimulation. The number and size of the colonies in patients were reduced compared to normal. The lymphocytic phenotype of colony cells was studied with monoclonal antibodies in colonies harvested from agar culture and in colonies expanded in liquid culture in the presence of TCGF. This study was performed in individual colonies and in pooled colonies. Colonies from normal controls contained a mixture of the OKT4+ and OKT8+ lymphocyte subsets. In contrast, colonies from the two patients contained essentially OKT4+ lymphocytes. The data indicate that, in the patients, progenitors of the OKT8+ subset are unresponsive to normal proliferative and/or differentiative stimuli under the present culture conditions. PMID:6606509

E-NTPDase and E-ADA activities in lymphocytes associated with the immune response of rats experimentally infected with Toxoplasma gondii.

PubMed

Tonin, Alexandre A; Da Silva, Aleksandro S; Ruchel, Jader B; Rezer, João F P; Camillo, Giovana; Faccio, Luciana; França, Raqueli T; Leal, Daniela B R; Duarte, Marta M M F; Vogel, Fernada F; de la Rue, Mario L; Lopes, Sonia T A

2013-10-01

An investigation of E-NTPDase and E-ADA activities in lymphocytes from rats experimentally infected with Toxoplasma gondii was carried out in this study. For this purpose, twenty four adult male Wistar rats were divided in two groups/four subgroups (A1 and A2; B1 and B2-6 animal/each group), with "A" as uninfected and "B" inoculated with T. gondii (RH strain). Sampling was performed on days 5 and 10 post-infection (p.i.), with evaluation of hemogram, immunoglobulins (IgM and IgG) and activity of E-NTPDase and E-ADA in lymphocytes. Enzymes essays showed ATP hydrolysis increased on days 5 (P<0.05) and 10 (P<0.01) p.i., as well as an increase of ADP hydrolysis on day 10 (P<0.01) p.i. E-ADA activity on lymphocytes was also increased in both evaluated periods (P<0.01). Based on E-NTPDase and E-ADA increased activities observed on lymphocytes, it is possible to suggest their involvement in an anti-inflammatory response, consisting of a modulatory response, preventing excessive tissue damage caused by the infection with Toxoplasma gondii. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2007-06-01

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

Monoclonal B lymphocytes with the characteristics of "indolent" chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts.

PubMed

Rawstron, Andy C; Green, Michael J; Kuzmicki, Anita; Kennedy, Ben; Fenton, James A L; Evans, Paul A S; O'Connor, Sheila J M; Richards, Stephen J; Morgan, Gareth J; Jack, Andrew S; Hillmen, Peter

2002-07-15

Molecular and cellular markers associated with malignant disease are frequently identified in healthy individuals. The relationship between these markers and clinical disease is not clear, except where a neoplastic cell population can be identified as in myeloma/monoclonal gammopathies of undetermined significance (MGUS). We have used the distinctive phenotype of chronic lymphocytic leukemia (CLL) cells to determine whether low levels of these cells can be identified in individuals with normal complete blood counts. CLL cells were identified by 4-color flow cytometric analysis of CD19/CD5/CD79b/CD20 expression in 910 outpatients over 40 years old. These outpatients were age- and sex-matched to the general population with normal hematologic parameters and no evident history of malignant disease. CLL phenotype cells were detectable in 3.5% of individuals at low level (median, 0.013; range, 0.002- 1.458 x 10(9) cells/L), and represented a minority of B lymphocytes (median, 11%; range, 3%-95%). Monoclonality was demonstrated by immunoglobulin light-chain restriction in all cases with CLL phenotype cells present and confirmed in a subset of cases by consensus-primer IgH-polymerase chain reaction. As in clinical disease, CLL phenotype cells were detected with a higher frequency in men (male-to-female ratio, 1.9:1) and elderly individuals (2.1% of 40- to 59-year-olds versus 5.0% of 60- to 89-year-olds, P =.01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20(wk)79b(wk)11a(-)22(wk)sIg(wk)CD38-, and where assessed had a high degree (4.8%-6.6%) of IgH somatic hypermutation. The monoclonal CLL phenotype cells present in otherwise healthy individuals may represent a very early stage of indolent CLL and should be useful in elucidating the mechanisms of leukemogenesis.

The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE.

PubMed

Halmer, Ramona; Davies, Laura; Liu, Yang; Fassbender, Klaus; Walter, Silke

2015-01-01

Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis. © 2015 The Author(s) Published by S. Karger AG, Basel.

Gadolinia depletion analysis by CASMO-4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Y.; Saji, E.; Toba, A.

1993-01-01

CASMO-4 is the most recent version of the lattice physics code CASMO introduced by Studsvik. The principal aspects of the CASMO-4 model that differ from the models in previous CASMO versions are as follows: (1) heterogeneous model for two-dimensional transport theory calculations; and (2) microregion depletion model for burnable absorbers, such as gadolinia. Of these aspects, the first has previously been benchmarked against measured data of critical experiments and Monte Carlo calculations, verifying the high degree of accuracy. To proceed with CASMO-4 benchmarking, it is desirable to benchmark the microregion depletion model, which enables CASMO-4 to calculate gadolinium depletion directlymore » without the need for precalculated MICBURN cross-section data. This paper presents the benchmarking results for the microregion depletion model in CASMO-4 using the measured data of depleted gadolinium rods.« less

Activation of microcarrier-attached lymphocytes in microgravity

NASA Technical Reports Server (NTRS)

Bechler, B.; Cogoli, A.; Cogoli-Greuter, M.; Muller, O.; Hunzinger, E.; Criswell, S. B.

1992-01-01

A technology has been developed to achieve optimal attachment of adhesion-independent lymphocytes to microcarrier beads. The activation of T-lymphocytes by concanavalin A was tested under microgravity conditions in an experiment carried out in space during the first Spacelab Life Science Mission. Activation, measured as the synthesis of deoxyribonucleic acid (DNA) and the production of interferon-gamma, more than doubled in attached lymphocytes in microgravity. The depression of the activation discovered in previous space experiments is due to an impairment not of the lymphocyte but of the macrophage function. The system described here may be useful for radiobiological investigations on the effect of high-energy particles and for testing the efficiency of the immune system in humans during the long-duration space flight planned in the future. The biotechnological significance of the increased lymphokine production in space remains to be assessed.

Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology

NASA Technical Reports Server (NTRS)

Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M.; Yin, Deling; Allan Mufson, R.; Zhou, Jian-nian

2003-01-01

Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immunosuppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis.

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

ClinicalTrials.gov

2013-09-27

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

An Ego Depletion Account of Aging Stereotypes' Effects on Health-Related Variables.

PubMed

Emile, Mélanie; d'Arripe-Longueville, Fabienne; Cheval, Boris; Amato, Massimiliano; Chalabaev, Aïna

2015-11-01

This study examined whether stereotypes may predict health outcomes independently from their internalization into the self. Specifically, we tested whether endorsement of negative age stereotypes in the physical activity (PA) domain is related to decreased subjective vitality among active older adults, illustrating ego depletion. This longitudinal study included 192 retired individuals aged 60-92 years who regularly participated in organized PA, and who completed the measures on three occasions (9-month period). Multilevel growth models tested whether within-person variation in age stereotypes endorsement across waves predicted subjective vitality, after controlling for self-perceptions of aging and relevant covariates. Results showed that (a) within-person increases in endorsement of age stereotypes of self-efficacy (b = 0.17, p < .01) were associated with increases in subjective vitality, (b) between-person mean difference in endorsement of age stereotypes of PA benefits (b = 0.21, p < .05) positively predicted subjective vitality, and (c) subjective vitality mediated the relationship between endorsement of self-efficacy stereotype and self-rated health. This study confirmed that endorsement of age stereotypes of PA predicted subjective vitality among active older adults. These results suggest that stereotypes may be related to health-related outcomes notably through ego depletion effects. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simulations and observations of plasma depletion, ion composition, and airglow emissions in two auroral ionospheric depletion experiments

NASA Technical Reports Server (NTRS)

Yau, A. W.; Whalen, B. A.; Harris, F. R.; Gattinger, R. L.; Pongratz, M. B.

1985-01-01

Observations of plasma depletion, ion composition modification, and airglow emissions in the Waterhole experiments are presented. The detailed ion chemistry and airglow emission processes related to the ionospheric hole formation in the experiment are examined, and observations are compared with computer simulation results. The latter indicate that the overall depletion rates in different parts of the depletion region are governed by different parameters.

Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells.

PubMed

Pène, Frédéric; Courtine, Emilie; Ouaaz, Fatah; Zuber, Benjamin; Sauneuf, Bertrand; Sirgo, Gonzalo; Rousseau, Christophe; Toubiana, Julie; Balloy, Viviane; Chignard, Michel; Mira, Jean-Paul; Chiche, Jean-Daniel

2009-12-01

Depletion of dendritic cells (DC) in secondary lymphoid organs is a hallmark of sepsis-induced immune dysfunction. In this setting, we investigated if Toll-like receptor (TLR)-dependent signaling might modulate the maturation process and the survival of DC. Using a model of sublethal polymicrobial sepsis induced by cecal ligation and puncture, we investigated the quantitative and functional features of spleen DC in wild-type, TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. By 24 h, a decrease in the relative percentage of CD11c(high) spleen DC occurred in wild-type mice but was prevented in TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. In wild-type mice, sepsis dramatically affected both CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) subsets. In all three types of knockout mice studied, the CD11c(+) CD8alpha(+) subset followed a depletion pattern similar to that for wild-type mice. In contrast, the loss of CD11c(+) CD8alpha(-) cells was attenuated in TLR2(-/-) and TLR4(-/-) mice and completely prevented in TLR2(-/-) TLR4(-/-) mice. Accordingly, apoptosis of spleen DC was increased in septic wild-type mice and inhibited in knockout mice. In addition we characterized the functional features of spleen DC obtained from septic mice. As shown by increased expression of major histocompatibility complex class II and CD86, polymicrobial sepsis induced maturation of DC, with subsequent increased capacity to prime T lymphocytes, similarly in wild-type and knockout mice. In response to CpG DNA stimulation, production of interleukin-12 was equally impaired in DC obtained from wild-type and knockout septic mice. In conclusion, although dispensable for the DC maturation process, TLR2 and TLR4 are involved in the mechanisms leading to depletion of spleen DC following polymicrobial sepsis.

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia, Version 1.2017.

PubMed

Wierda, William G; Zelenetz, Andrew D; Gordon, Leo I; Abramson, Jeremy S; Advani, Ranjana H; Andreadis, C Babis; Bartlett, Nancy; Byrd, John C; Caimi, Paolo; Fayad, Luis E; Fisher, Richard I; Glenn, Martha J; Habermann, Thomas M; Harris, Nancy Lee; Hernandez-Ilizaliturri, Francisco; Hoppe, Richard T; Horwitz, Steven M; Kaminski, Mark S; Kelsey, Christopher R; Kim, Youn H; Krivacic, Susan; LaCasce, Ann S; Martin, Michael G; Nademanee, Auayporn; Porcu, Pierluigi; Press, Oliver; Rabinovitch, Rachel; Reddy, Nishitha; Reid, Erin; Roberts, Kenneth; Saad, Ayman A; Snyder, Erin D; Sokol, Lubomir; Swinnen, Lode J; Vose, Julie M; Yahalom, Joachim; Dwyer, Mary A; Sundar, Hema

2017-03-01

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL. Copyright © 2017 by the National Comprehensive Cancer Network.

The Development of Adult Innate Lymphoid Cells

PubMed Central

Yang, Qi; Bhandoola, Avinash

2016-01-01

Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

Isolation and characterization of lymphocyte-like cells from a lamprey

PubMed Central

Mayer, Werner E.; Uinuk-ool, Tatiana; Tichy, Herbert; Gartland, Lanier A.; Klein, Jan; Cooper, Max D.

2002-01-01

Lymphocyte-like cells in the intestine of the sea lamprey, Petromyzon marinus, were isolated by flow cytometry under light-scatter conditions used for the purification of mouse intestinal lymphocytes. The purified lamprey cells were morphologically indistinguishable from mammalian lymphocytes. A cDNA library was prepared from the lamprey lymphocyte-like cells, and more than 8,000 randomly selected clones were sequenced. Homology searches comparing these ESTs with sequences deposited in the databases led to the identification of numerous genes homologous to those predominantly or characteristically expressed in mammalian lymphocytes, which included genes controlling lymphopoiesis, intracellular signaling, proliferation, migration, and involvement of lymphocytes in innate immune responses. Genes closely related to those that in gnathostomes control antigen processing and transport of antigenic peptides could be ascertained, although no sequences with significant similarity to MHC, T cell receptor, or Ig genes were found. The data suggest that the evolution of lymphocytes in the lamprey has reached a stage poised for the emergence of adaptive immunity. PMID:12388781

Effect of infection with bovine leukosis virus on lymphocyte proliferation and apoptosis in dairy cattle.

PubMed

Erskine, Ronald J; Corl, Christine M; Gandy, Jeffery C; Sordillo, Lorraine M

2011-08-01

To determine effects of infection with bovine leukosis virus (BLV) on lymphocyte proliferation and apoptosis in dairy cattle. 27 adult Holstein cows. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood from lactating Holstein cows seronegative for BLV (n = 9 cows), seropositive for BLV and aleukemic (aleukemic; 9), and seropositive for BLV and persistently lymphocytotic (PL; 9). Isolated PBMCs were assayed for mitogen-induced proliferation and were analyzed by means of flow cytometry. The PBMCs from a subset of each group were assayed for apoptosis, caspase-9 activity, and expression of selected genes related to apoptosis. PL cows had significantly higher total lymphocyte counts and significantly lower proportions of T-lymphocyte populations than did BLV-negative and aleukemic cows. Both groups of BLV-infected cows had significantly higher proportions of B cells and major histocompatibility complex II-expressing cells than did BLV-negative cows. Proliferation with concanavalin A was significantly lower for PL cows, compared with proliferation for BLV-negative cows. Pokeweed mitogen-induced proliferation was significantly higher for aleukemic and PL cows than for BLV-negative cows. Gene expression of apoptosis-inhibitory proteins BCL2 and BCL2L1 was significantly higher for aleukemic cows and expression of BCL2 was significantly higher for PL cows than for BLV-negative cows. Cattle infected with BLV had marked changes in PBMC populations accompanied by alterations in proliferation and apoptosis mechanisms. Because the relative distribution and function of lymphocyte populations are critical for immune competence, additional studies are needed to investigate the ability of BLV-infected cattle to respond to infectious challenge.

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells.

PubMed

Dardalhon, V; Jaleco, S; Kinet, S; Herpers, B; Steinberg, M; Ferrand, C; Froger, D; Leveau, C; Tiberghien, P; Charneau, P; Noraz, N; Taylor, N

2001-07-31

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4(+) cells proliferated in response to IL-7, whereas naive UC CD4(+) lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G(1b) phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4(+) lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4(+) UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4(+) T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates.

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells

PubMed Central

Dardalhon, Valérie; Jaleco, Sara; Kinet, Sandrina; Herpers, Bjorn; Steinberg, Marcos; Ferrand, Christophe; Froger, Delphine; Leveau, Christelle; Tiberghien, Pierre; Charneau, Pierre; Noraz, Nelly; Taylor, Naomi

2001-01-01

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4+ cells proliferated in response to IL-7, whereas naive UC CD4+ lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G1b phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4+ lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4+ UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4+ T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates. PMID:11470908

Differences in Aspergillus-specific immune recovery between T-cell-replete and T-cell-depleted hematopoietic transplants.

PubMed

Perruccio, Katia; Topini, Fabiana; Tosti, Antonella; Gazzola, Maria Vittoria; Messina, Chiara; Martelli, Massimo F; Caniglia, Maurizio; Velardi, Andrea; Cesaro, Simone

2015-12-01

After hematopoietic stem cell transplantation, invasive aspergillosis remains one of the most lethal infections. Susceptibility may be due to prophylaxis and treatment of graft-vs.-host disease in T-cell-replete transplants, and delayed immune rebuilding due to T-cell depletion in haploidentical transplantation. We monitored CD4(+) T-cell recovery and anti-Aspergillus immune competence in pediatric recipients of T-cell-replete matched transplants and of prevalently adult recipients of T-cell-depleted matched or haploidentical transplants for hematological malignancies. Although CD4(+) T-cell counts were higher in T-cell-replete transplant recipients at all post-transplant time points, Aspergillus-specific T cells were first detected 15-18 months after T-cell-replete matched, 7-9 months after T-cell-depleted matched, and 9-12 months after haploidentical transplantation, respectively. Incidence of invasive aspergillosis was 22% with 10% mortality after T-cell-replete transplants, 0% after T-cell-depleted matched, and 7% with 4% mortality after haploidentical transplants. Although T-cell counts were significantly higher after T-cell-replete transplants, post-transplant immune suppression/GvHD appeared to impair their function. Specific Aspergillus immune competence recovered faster after T-cell-depleted transplants, whether matched or haploidentical. T-cell-replete transplants were associated with a higher incidence of invasive aspergillosis and Aspergillus-related deaths. These results showed that T-cell depletion without post-transplant immunosuppression is associated to a faster immune recovery than T-cell-replete transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Persistent depletion of plasma gelsolin (pGSN) after exposure of mice to heavy silicon ions.

PubMed

Rithidech, Kanokporn Noy; Reungpatthanaphong, Paiboon; Tungjai, Montree; Jangiam, Witawat; Honikel, Louise; Whorton, Elbert B

2018-05-01

Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon ( 28 Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells. We evaluated the levels of pGSN in plasma collected from groups of mice (5 mice in each) at 1 week (wk) and 1 month (1 mo) after exposure whole body to different doses of 28 Si ions, i.e. 0, 0.1, 0.25, or 0.5 Gy (2 fractionated exposures, 15 days apart that totaled each selected dose). In the same mouse, the measurements of pGSN levels were coupled with the quantitation of injuries in the lung, determined by (a) the levels of cleaved poly (ADP-ribose) polymerase (cleaved-PARP), a marker of apoptotic cell-death, (b) the levels of activated nuclear factor-kappa B (NF-κB) and selected cytokines, i.e. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, from tissue-lysates of the lung. Further, the ratio of neutrophils and lymphocytes (N/L) was determined in the same mouse. Our data indicated: (i) the magnitude of pGSN depletion was dependent to radiation dose at both harvest times, (ii) a persistent depletion of pGSN up to 1 mo post-exposure to 0.25 or 0.5 Gy of 28 Si ions, (iii) an inverse-correlation between pGSN depletion and increased levels of cleaved-PARP, including activated NF-κB/pro-inflammatory cytokines in the lung, and (iv) at both harvest times, statistically significant increases in the N/L ratio in groups of mice exposed to 0.5 Gy only. Our findings suggested that depletion in p

Persistent depletion of plasma gelsolin (pGSN) after exposure of mice to heavy silicon ions

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn Noy; Reungpatthanaphong, Paiboon; Tungjai, Montree; Jangiam, Witawat; Honikel, Louise; Whorton, Elbert B.

2018-05-01

Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon (28Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells. We evaluated the levels of pGSN in plasma collected from groups of mice (5 mice in each) at 1 week (wk) and 1 month (1 mo) after exposure whole body to different doses of 28Si ions, i.e. 0, 0.1, 0.25, or 0.5 Gy (2 fractionated exposures, 15 days apart that totaled each selected dose). In the same mouse, the measurements of pGSN levels were coupled with the quantitation of injuries in the lung, determined by (a) the levels of cleaved poly (ADP-ribose) polymerase (cleaved-PARP), a marker of apoptotic cell-death, (b) the levels of activated nuclear factor-kappa B (NF-κB) and selected cytokines, i.e. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, from tissue-lysates of the lung. Further, the ratio of neutrophils and lymphocytes (N/L) was determined in the same mouse. Our data indicated: (i) the magnitude of pGSN depletion was dependent to radiation dose at both harvest times, (ii) a persistent depletion of pGSN up to 1 mo post-exposure to 0.25 or 0.5 Gy of 28Si ions, (iii) an inverse-correlation between pGSN depletion and increased levels of cleaved-PARP, including activated NF-κB/pro-inflammatory cytokines in the lung, and (iv) at both harvest times, statistically significant increases in the N/L ratio in groups of mice exposed to 0.5 Gy only. Our findings suggested that depletion in pGSN levels

The effect of veiled cells on lymphocyte function.

PubMed

Balfour, B; O'Brien, J A; Perera, M; Clarke, J; Sumerska, T; Knight, S C

1982-01-01

The response of lymphocytes to stimulation with Con A has been studied in the presence of veiled cells collected from the afferent lymph. In these enriched cultures the response occurred earlier with smaller numbers of lymphocytes and at lower concentrations of Con A. Veiled cells also caused clumping of lymphocytes in unstimulated cultures. In stimulated cultures small cells with veil-like projections appeared after 48 hr, but were not seen in unstimulated cultures.

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

PubMed Central

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

48 CFR 52.223-11 - Ozone-Depleting Substances.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

48 CFR 52.223-11 - Ozone-Depleting Substances.

Code of Federal Regulations, 2013 CFR

2013-10-01

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

48 CFR 52.223-11 - Ozone-Depleting Substances.

Code of Federal Regulations, 2014 CFR

2014-10-01

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

48 CFR 52.223-11 - Ozone-Depleting Substances.

Code of Federal Regulations, 2012 CFR

2012-10-01

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

48 CFR 52.223-11 - Ozone-Depleting Substances.

Code of Federal Regulations, 2011 CFR

2011-10-01

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

Selective Regulation of Human Immunodeficiency Virus-Infected CD4+ Lymphocytes by a Synthetic Immunomodulator Leads to Potent Virus Suppression In Vitro and in hu-PBL-SCID Mice

PubMed Central

Bahr, George M.; Darcissac, Edith C. A.; Castéran, Nathalie; Amiel, Corinne; Cocude, Cécile; Truong, Marie-José; Dewulf, Joëlle; Capron, André; Mouton, Yves

2001-01-01

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants. This activity correlated with reduced viral transcripts and proviral DNA, was evident in cultures harboring R5, X4-R5, or X4 HIV-1 isolates, was not linked to inhibition of cellular DNA synthesis, and did not correlate with β-chemokine release. Moreover, c-myc mRNA expression was down-regulated in Murabutide-treated cells, suggesting potential interference of the immunomodulator with the nuclear transport of viral preintegration complexes. On the other hand, daily treatment of HIV-1-infected hu-PBL-SCID mice with Murabutide significantly reduced the viral loads in plasma and the proviral DNA content in human peritoneal cells. These results are the first to demonstrate that a clinically acceptable synthetic immunomodulator with an ability to enhance the host's nonspecific immune defense mechanisms against infections can directly regulate cellular factors in infected lymphocytes, leading to controlled HIV-1 replication. PMID:11435574

New Approach For Prediction Groundwater Depletion

NASA Astrophysics Data System (ADS)

Moustafa, Mahmoud

2017-01-01

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

Necroptosis Takes Place in Human Immunodeficiency Virus Type-1 (HIV-1)-Infected CD4+ T Lymphocytes

PubMed Central

Pan, Ting; Wu, Shuangxin; He, Xin; Luo, Haihua; Zhang, Yijun; Fan, Miaomiao; Geng, Guannan; Ruiz, Vivian Clarke; Zhang, Jim; Mills, Lisa; Bai, Chuan; Zhang, Hui

2014-01-01

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis. PMID:24714696

Monoclonal antibodies to the equine CD2 T lymphocyte marker, to a pan-granulocyte/monocyte marker and to a unique pan-B lymphocyte marker.

PubMed

Tumas, D B; Brassfield, A L; Travenor, A S; Hines, M T; Davis, W C; McGuire, T C

1994-12-01

Murine monoclonal antibodies, HB88A, B29A and DH59B separately identify the CD2 T lymphocyte molecule, a unique pan-B lymphocyte surface marker and a pan-granulocyte/monocyte surface molecule, respectively, in the horse. Specificity was shown by two-color immunofluorescent flow cytometry and immunofluorescent microscopy. MAb HB88A reacted with a 52 kDa pan-T lymphocyte molecule present on 75% +/- 7 of peripheral blood lymphocytes (PBL) (n = 15 horses). It also reacted with lymphocytes restricted to T lymphocyte dependent areas of lymph node and spleen. Specificity of mAb HB88A to CD2 was demonstrated by its reactivity to COS7 cells which expressed a transfected 1.5 kb equine lymphocyte c-DNA clone having 77.5% overall sequence homology with human CD2 c-DNA. MAb B29A reacted with a pan-B lymphocyte specific cell surface complex, 143, 72, 50, 40, 27 and 14.5 kDa, present on 19% +/- 7 of PBL (n = 15 horses). This complex has not been described in the horse or other species. MAb DH59B reacted with a 96 kDa pan-granulocyte/monocyte specific surface protein and identified macrophages and Kupffer cells in equine tissue sections. Together these mAbs can be used to identify and quantitate the major constituents of equine leukocytes.

Podocyte Depletion in Thin GBM and Alport Syndrome.

PubMed

Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

2016-01-01

The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman's capsule) were present at 30-50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

Cardiomyocyte marker expression in a human lymphocyte cell line using mouse cardiomyocyte extract.

PubMed

Vojdani, Zahra; Tavakolinejad, Sima; Talaei-Khozani, Tahereh; Esmaeilpour, Tahereh; Rasooli, Manuchehr

2011-03-01

Cell transplantation shows potential for the treatment of cardiac diseases. Embryonic stem cells, cord blood and mesenchymal stem cells have been suggested as sources for transplantation therapy. Because of some technical limitations with the use of stem cells, transdifferentiation of fully differentiated cells is a potentially useful alternative. We investigated whether human peripheral blood cells could transdifferentiate into cardiomyocyte. Transdifferentiation was induced in a human B lymphocyte cell line (Raji). Cardiomyocyte extract was prepared from adult mouse cardiomyocytes. The cells were treated with 5-aza-2-deoxycytidine and trichostatin A, permeabilized with streptolysin O, and exposed to the mouse cardiomyocyte extract. They were cultured for 10 days, 3 weeks and 4 weeks. Cardiomyocyte markers were detected with immunohistochemistry and flow cytometry. Immunocytochemistry revealed that some cells expressed myosin heavy chain, α-actinin and cardiac troponin T after 3 and 4 weeks. Flow cytometry confirmed these data. In cells exposed to trichostatin A and 5-aza-2-deoxycytidine and permeabilized in the presence of the cardiomyocyte extract, troponin T expression was seen in 3.53% of the cells and 3.11% of them expressed α-actinin. After exposure to the cardiomyocyte extract, some permeabilized cells adhered to the plate loosely; however, the morphology did not change significantly, and they continued to show a rounded shape after 4 weeks. Our treated lymphocytes expressed cardiomyocyte markers. Our results suggest that lymphocytes may be useful in future research as a source of cells for reprogramming procedures.

Increased mitogenic response in lymphocytes from chronically centrifuged mice

NASA Technical Reports Server (NTRS)

Mueller, Otfried; Hunzinger, E.; Cogoli, Augusto; Bechler, B.; Lee, J.; Moore, J.; Duke, J.

1990-01-01

The effects upon the mitogenic response of splenic lymphocytes when exposing mice to prolonged hypergravity conditions (3.5 G for 1 year) were studied. Cultures of splenic lymphocytes isolated from both centrifuged and control (1 G) animals were stimulated with Concanavalin A and the response measured using both morphological and biochemical means. Lymphocytes obtained from centrifuged mice exhibited much higher activation rates (as measured by the incorporation of H-3 thymidine) and larger cell aggregates consisting of more lymphoblasts and mitotic figures than those observed in non centrifuged control animals. Isolated splenic lymphocytes thus appear to have been conditioned by hypergravity state.

Cellular energy metabolism in T-lymphocytes.

PubMed

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.

Erythrocyte depletion from bone marrow: performance evaluation after 50 clinical-scale depletions with Spectra Optia BMC.

PubMed

Kim-Wanner, Soo-Zin; Bug, Gesine; Steinmann, Juliane; Ajib, Salem; Sorg, Nadine; Poppe, Carolin; Bunos, Milica; Wingenfeld, Eva; Hümmer, Christiane; Luxembourg, Beate; Seifried, Erhard; Bonig, Halvard

2017-08-11

Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions. Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite. Product quality was assessed before and after processing for volume, RBC and leukocyte content; RBC-depletion and stem cell (CD34+ cells) recovery was calculated there from. Clinical engraftment data were collected from 26/45 allogeneic recipients. Median RBC removal was 98.2% (range 90.8-99.1%), median CD34+ cell recovery was 93.6%, minimum recovery being 72%, total product volume was reduced to 7.5% (range 4.7-23.0%). Products engrafted with expected probability and kinetics. Performance indicators were stable over time. Spectra Optia BMC is a robust and efficient technology for RBC-depletion and volume reduction of BM, providing near-complete RBC removal and excellent CD34+ cell recovery.

Changes in gravity inhibit lymphocyte locomotion through type I collagen

NASA Technical Reports Server (NTRS)

Pellis, N. R.; Goodwin, T. J.; Risin, D.; McIntyre, B. W.; Pizzini, R. P.; Cooper, D.; Baker, T. L.; Spaulding, G. F.

1997-01-01

Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes

Revisiting Antarctic Ozone Depletion

NASA Astrophysics Data System (ADS)

Grooß, Jens-Uwe; Tritscher, Ines; Müller, Rolf

2015-04-01

Antarctic ozone depletion is known for almost three decades and it has been well settled that it is caused by chlorine catalysed ozone depletion inside the polar vortex. However, there are still some details, which need to be clarified. In particular, there is a current debate on the relative importance of liquid aerosol and crystalline NAT and ice particles for chlorine activation. Particles have a threefold impact on polar chlorine chemistry, temporary removal of HNO3 from the gas-phase (uptake), permanent removal of HNO3 from the atmosphere (denitrification), and chlorine activation through heterogeneous reactions. We have performed simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) employing a recently developed algorithm for saturation-dependent NAT nucleation for the Antarctic winters 2011 and 2012. The simulation results are compared with different satellite observations. With the help of these simulations, we investigate the role of the different processes responsible for chlorine activation and ozone depletion. Especially the sensitivity with respect to the particle type has been investigated. If temperatures are artificially forced to only allow cold binary liquid aerosol, the simulation still shows significant chlorine activation and ozone depletion. The results of the 3-D Chemical Transport Model CLaMS simulations differ from purely Lagrangian longtime trajectory box model simulations which indicates the importance of mixing processes.

Establishment of a novel endothelial target mouse model of a typhus group rickettsiosis: evidence for critical roles for gamma interferon and CD8 T lymphocytes.

PubMed

Walker, D H; Popov, V L; Feng, H M

2000-09-01

A mouse model of typhus rickettsiosis that reproduces the hematogenous dissemination to the critical target organs, including brain, lungs, heart, and kidneys, primary endothelial and, to a lesser degree, macrophage intracellular rickettsial infection, and typical vascular-based lesions of louse-borne typhus and murine typhus was established. Intravenous inoculation of C3H/HeN mice with Rickettsia typhi caused disease with a duration of the incubation period and mortality rate that were dependent on the infective dose of rickettsiae. Lethal infection was associated with high concentrations of R. typhi in the lungs and brain, despite a brisker humoral immune response to the rickettsiae than in the sublethal infection. Gamma interferon and CD8 T lymphocytes were demonstrated to be crucial to clearance of the rickettsiae and recovery from infection in experiments in which specific monoclonal antibodies were administered to deplete these components. Death of animals depleted of gamma interferon or CD8 T lymphocytes was associated with overwhelming rickettsial infection demonstrated by titers of infectious rickettsiae and by immunohistochemistry. An effective antirickettsial immune response was associated with elevated serum concentrations of IL-12 on Day 5 and increased secretion of IL-12 by concanavalin-A-stimulated spleen cells on Day 5. Evidence for transient suppression of the immune response consisted of marked reduction in the secretion of IL-2 and IL-12 by concanavalin-A-stimulated spleen cells on Days 10 and 15. This model offers excellent opportunities for study of attenuation and pathogenetic mechanisms of typhus rickettsiae, which are established biologic weapons of potential use in bioterrorism.

Acute Lymphocytic Leukemia

MedlinePlus

... radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia. Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of acute ...

Transient Treg depletion enhances therapeutic anti-cancer vaccination.

PubMed

Fisher, Scott A; Aston, Wayne J; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L; Solin, Jessica N; Ma, Shaokang; Lesterhuis, W Joost; Dick, Ian; Holt, Robert A; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A

2017-03-01

Regulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. DTX specifically depleted Treg in a transient, dose-dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor-peptide vaccination. BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor-specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.

Old and New Lymphocyte Players in Inflammatory Bowel Disease.

PubMed

Giuffrida, Paolo; Corazza, Gino Roberto; Di Sabatino, Antonio

2018-02-01

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic intestinal inflammatory disorder characterized by diffuse accumulation of lymphocytes in the gut mucosa as a consequence of over-expression of endothelial adhesion molecules. The infiltrating lymphocytes have been identified as subsets of T cells, including T helper (Th)1 cells, Th17 cells, and regulatory T cells. The function of these lymphocyte subpopulations in the development of IBD is well-known, since they produce a number of pro-inflammatory cytokines, such as interferon-γ and interleukin-17A, which in turn activate mucosal proteases, thus leading to the development of intestinal lesions, i.e., ulcers, fistulas, abscesses, and strictures. However, the immune mechanisms underlying IBD are not yet fully understood, and knowledge about the function of newly discovered lymphocytes, including Th9 cells, innate lymphoid cells, mucosal-associated invariant T cells, and natural killer T cells, might add new pieces to the complex puzzle of IBD pathogenesis. This review summarizes the recent advances in the understanding of the role of mucosal lymphocytes in chronic intestinal inflammation and deals with the therapeutic potential of lymphocyte-targeting drugs in IBD patients.

Physiological implications of anthropogenic environmental calcium depletion

Treesearch

Catherine H. Borer; Paul G. Schaberg; Donald H. DeHayes; Gary J. Hawley

2001-01-01

Recent evidence indicates that numerous anthropogenic factors can deplete calcium (Ca) from forested ecosystems. Although it is difficult to quantify the extent of this depletion, some reports indicate that the magnitude of Ca losses may be substantial. The potential for Ca depletion raises important questions about tree health. Only a fraction of foliar Ca is...

A new definition of maternal depletion syndrome.

PubMed Central

Winkvist, A; Rasmussen, K M; Habicht, J P

1992-01-01

BACKGROUND. Although the term "maternal depletion syndrome" has been commonly used to explain poor maternal and infant health, whether such a syndrome actually exists remains unclear. This uncertainty may be due to the lack of a clear definition of the syndrome and the absence of theoretical frameworks that account for the many factors related to reproductive nutrition. METHODS. We propose a new definition of maternal depletion syndrome within a framework that accounts for potential confounding factors. RESULTS. Our conceptual framework distinguishes between childbearing pattern and inadequate diet as causes of poor maternal health; hence, our definition of maternal depletion syndrome has both biological and practical meaning. The new definition is based on overall change in maternal nutritional status over one reproductive cycle in relation to possible depletion and repletion phases and in relation to initial nutritional status. CONCLUSIONS. The empirical application of this approach should permit the testing of the existence of maternal depletion syndrome in the developing world, and the distinction between populations where family planning will alleviate maternal depletion and those in which an improved diet is also necessary. PMID:1566948

ANATOMY OF DEPLETED INTERPLANETARY CORONAL MASS EJECTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kocher, M.; Lepri, S. T.; Landi, E.

We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE /SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C{sup 6+}/C{sup 5+} and O{sup 7+}/O{sup 6+} depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property ofmore » significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.« less

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation.

PubMed

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.

Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus

PubMed Central

Byleveld, M; Pang, G T; Clancy, R L; Roberts, D C K

2000-01-01

The effect of a fish oil diet on virus-specific cytotoxicity and lymphocyte proliferation was investigated. Mice were fed fish oil (17 g fish oil and 3 g sunflower/100 g) or beef tallow (17 g tallow and 3 g sunflower/100 g) diets for 14 days before intranasal challenge with influenza virus. At day 5 after infection, lung virus-specific T lymphocyte, but not macrophage or natural killer (NK) cell, cytotoxicity was significantly lower in mice fed fish oil, while bronchial lymph node cell proliferation to virus was significantly higher. In mice fed fish oil, spleen cell proliferation to virus was also significantly higher following immunization. The results showed that, despite improved lymphocyte proliferation, fish oil impairs primary virus-specific T lymphocyte cytotoxicity. This impairment may explain the delayed virus clearance that we have previously reported in infected mice fed the fish oil diet. PMID:10632664

Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus.

PubMed

Byleveld, M; Pang, G T; Clancy, R L; Roberts, D C

2000-02-01

The effect of a fish oil diet on virus-specific cytotoxicity and lymphocyte proliferation was investigated. Mice were fed fish oil (17 g fish oil and 3 g sunflower/100 g) or beef tallow (17 g tallow and 3 g sunflower/100 g) diets for 14 days before intranasal challenge with influenza virus. At day 5 after infection, lung virus-specific T lymphocyte, but not macrophage or natural killer (NK) cell, cytotoxicity was significantly lower in mice fed fish oil, while bronchial lymph node cell proliferation to virus was significantly higher. In mice fed fish oil, spleen cell proliferation to virus was also significantly higher following immunization. The results showed that, despite improved lymphocyte proliferation, fish oil impairs primary virus-specific T lymphocyte cytotoxicity. This impairment may explain the delayed virus clearance that we have previously reported in infected mice fed the fish oil diet.

Effects of lifestyle on micronuclei frequency in human lymphocytes in Japanese hard-metal workers.

PubMed

Huang, Peixin; Huang, Bin; Weng, Huachun; Nakayama, Kunio; Morimoto, Kanehisa

2009-04-01

The risks of cardiovascular disease, cancer, and other major causes of mortality are largely attributable to lifestyle factors such as smoking, alcohol drinking, hours of working and sleeping, physical activity, diet, and stress. Earlier studies have suggested that an unhealthy lifestyle is also associated with increased lymphocyte sensitivity to mutagens, oxidative DNA damage level, and leukocyte DNA damage. In order to explore the genotoxicity of unhealthy lifestyle, we evaluated the effect of overall lifestyle as well as some individual lifestyle factors on micronuclei (MN) frequency in cultured human lymphocytes. The study was conducted among 208 healthy adult (19 to 59 years) male Japanese hard-metal workers. The subjects were divided into groups according to their self-reported good, moderate, and poor lifestyles based on their responses to a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress), the presence or absence of each of which was summed to obtain a health practice index (HPI: range 0-8). Peripheral blood was taken and the cytokinesis-block micronuclei (CBMN) assay was performed. Total lifestyle quality as measured by the HPI was strongly negatively associated with MN frequency in cultured human lymphocytes (p<0.01). Nutritional imbalance, lack of regular exercise (<2 times per week), insufficient sleep (< or =6 h per day), and overtime working (> or =9 h per day) each contributed significantly to higher MN frequency (all p<0.05). In the smoker group, a significantly higher MN frequency was only found in heavy smokers (p<0.05). On the other hand, mental stress, eating breakfast, and alcohol drinking had no effect on MN frequency. Taken together, these findings indicate that poor lifestyle habits significantly increase MN frequency in human lymphocytes.

Transient Treg depletion enhances therapeutic anti‐cancer vaccination

PubMed Central

Aston, Wayne J.; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L.; Solin, Jessica N.; Ma, Shaokang; Lesterhuis, W. Joost; Dick, Ian; Holt, Robert A.; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A.

2016-01-01

Abstract Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination. Conclusions BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies. PMID:28250921

Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

PubMed

Zhelev, Zhivko; Ivanova, Donika; Lazarova, Desislava; Aoki, Ichio; Bakalova, Rumiana; Saga, Tsuneo

2016-04-01

The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects. Copyright© 2016 International Institute of

Effect of spaceflight on lymphocyte proliferation and interleukin-2 production

NASA Technical Reports Server (NTRS)

Nash, Patricia V.; Konstantinova, Irina V.; Fuchs, Boris B.; Rakhmilevich, Alexandr L.; Lesniak, A. T.; Mastro, Andrea M.

1992-01-01

In this study, inguinal lymp node lymphocytes from rats flown on the Cosmos 2044 mission were tested for proliferation and interleukin-2 (IL-2) production. Cells cultured with mitogenic lectins, phorbol ester, and calcium ionophore, or T-cell mitogen and lymphokine, were assayed for DNA synthesis by (H-3) thymidine incorporation. Lymphocytes incubated with a T-cell mitogen alone also were tested for IL-2 production. Proliferation of lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from control and flown rats produced similar amounts of IL-23. Thus microgravity may act on lymphocytes in a tissue-specific manner, a new finding that could impact on the evaluation of spaceflight effects on immunocompetence.

Depletion sensitivity predicts unhealthy snack purchases.

PubMed

Salmon, Stefanie J; Adriaanse, Marieke A; Fennis, Bob M; De Vet, Emely; De Ridder, Denise T D

2016-01-01

The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose weight on snack purchase behavior were explored. Participants included in the study were instructed to report every snack they bought over the course of one week. The dependent variables were the number of healthy and unhealthy snacks purchased. The results of the present study demonstrate that depletion sensitivity predicts the amount of unhealthy (but not healthy) snacks bought. The more sensitive people are to depletion, the more unhealthy snacks they buy. Moreover, there was some tentative evidence that this relation is more pronounced for people with a weak as opposed to a strong goal to lose weight, suggesting that a strong goal to lose weight may function as a motivational buffer against self-control failures. All in all, these findings provide evidence for the external validity of depletion sensitivity and the relevance of this construct in the domain of eating behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.

PubMed

Czarnowicki, Tali; Esaki, Hitokazu; Gonzalez, Juana; Malajian, Dana; Shemer, Avner; Noda, Shinji; Talasila, Sreya; Berry, Adam; Gray, Jayla; Becker, Lauren; Estrada, Yeriel; Xu, Hui; Zheng, Xiuzhong; Suárez-Fariñas, Mayte; Krueger, James G; Paller, Amy S; Guttman-Yassky, Emma

2015-10-01

Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01). These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections

Lymphocyte count as a sign of immunoparalysis and its correlation with nutritional status in pediatric intensive care patients with sepsis: A pilot study.

PubMed

Manzoli, Talita Freitas; Delgado, Artur Figueiredo; Troster, Eduardo Juan; de Carvalho, Werther Brunow; Antunes, Ana Caroline Barreto; Marques, Desirée Mayara; Zamberlan, Patrícia

2016-11-01

Developing malnutrition during hospitalization is well recognized worldwide, and children are at a relatively higher risk for malnutrition than adults. Malnutrition can lead to immune dysfunction, which is associated with a higher mortality rate due to sepsis, the most frequent cause of death in pediatric intensive care units (PICUs). The aim of this study was to investigate whether malnourished patients are more likely to have relative or absolute lymphopenia and, consequently, worse prognoses. We enrolled 14 consecutive patients with sepsis whose legal representatives provided written informed consent. Patients were classified as normal or malnourished based on anthropometric measurements. As an additional evaluation of nutritional status, serum albumin and zinc were measured on the 1st and 7th days of hospitalization. Lymphocyte count was also measured on the 1st and 7th days. Clinicaltrials.gov: NCT02698683. Malnutrition prevalence rates were 33.3% and 42.8% based on weight and height, respectively. Laboratory analyses revealed a reduction of serum albumin in 100% of patients and reduction of zinc in 93.3% of patients. A total of 35% of patients had fewer than 500 lymphocytes/mm3 on their first day in the PICU. Lymphocyte counts and zinc concentrations significantly increased during hospitalization. Nutritional evaluations, including anthropometric measurements, were not correlated with lymphocyte counts. Lymphocyte counts concomitantly increased with zinc levels, suggesting that micronutrient supplementation benefits patients with sepsis.

Is Ego Depletion Real? An Analysis of Arguments.

PubMed

Friese, Malte; Loschelder, David D; Gieseler, Karolin; Frankenbach, Julius; Inzlicht, Michael

2018-03-01

An influential line of research suggests that initial bouts of self-control increase the susceptibility to self-control failure (ego depletion effect). Despite seemingly abundant evidence, some researchers have suggested that evidence for ego depletion was the sole result of publication bias and p-hacking, with the true effect being indistinguishable from zero. Here, we examine (a) whether the evidence brought forward against ego depletion will convince a proponent that ego depletion does not exist and (b) whether arguments that could be brought forward in defense of ego depletion will convince a skeptic that ego depletion does exist. We conclude that despite several hundred published studies, the available evidence is inconclusive. Both additional empirical and theoretical works are needed to make a compelling case for either side of the debate. We discuss necessary steps for future work toward this aim.

Self-Regulatory Capacities Are Depleted in a Domain-Specific Manner

PubMed Central

Zhang, Rui; Stock, Ann-Kathrin; Rzepus, Anneka; Beste, Christian

2017-01-01

Performing an act of self-regulation such as making decisions has been suggested to deplete a common limited resource, which impairs all subsequent self-regulatory actions (ego depletion theory). It has however remained unclear whether self-referred decisions truly impair behavioral control even in seemingly unrelated cognitive domains, and which neurophysiological mechanisms are affected by these potential depletion effects. In the current study, we therefore used an inter-individual design to compare two kinds of depletion, namely a self-referred choice-based depletion and a categorization-based switching depletion, to a non-depleted control group. We used a backward inhibition (BI) paradigm to assess the effects of depletion on task switching and associated inhibition processes. It was combined with EEG and source localization techniques to assess both behavioral and neurophysiological depletion effects. The results challenge the ego depletion theory in its current form: Opposing the theory’s prediction of a general limited resource, which should have yielded comparable effects in both depletion groups, or maybe even a larger depletion in the self-referred choice group, there were stronger performance impairments following a task domain-specific depletion (i.e., the switching-based depletion) than following a depletion based on self-referred choices. This suggests at least partly separate and independent resources for various cognitive control processes rather than just one joint resource for all self-regulation activities. The implications are crucial to consider for people making frequent far-reaching decisions e.g., in law or economy. PMID:29033798

Self-Regulatory Capacities Are Depleted in a Domain-Specific Manner.

PubMed

Zhang, Rui; Stock, Ann-Kathrin; Rzepus, Anneka; Beste, Christian

2017-01-01

Performing an act of self-regulation such as making decisions has been suggested to deplete a common limited resource, which impairs all subsequent self-regulatory actions (ego depletion theory). It has however remained unclear whether self-referred decisions truly impair behavioral control even in seemingly unrelated cognitive domains, and which neurophysiological mechanisms are affected by these potential depletion effects. In the current study, we therefore used an inter-individual design to compare two kinds of depletion, namely a self-referred choice-based depletion and a categorization-based switching depletion, to a non-depleted control group. We used a backward inhibition (BI) paradigm to assess the effects of depletion on task switching and associated inhibition processes. It was combined with EEG and source localization techniques to assess both behavioral and neurophysiological depletion effects. The results challenge the ego depletion theory in its current form: Opposing the theory's prediction of a general limited resource, which should have yielded comparable effects in both depletion groups, or maybe even a larger depletion in the self-referred choice group, there were stronger performance impairments following a task domain-specific depletion (i.e., the switching-based depletion) than following a depletion based on self-referred choices. This suggests at least partly separate and independent resources for various cognitive control processes rather than just one joint resource for all self-regulation activities. The implications are crucial to consider for people making frequent far-reaching decisions e.g., in law or economy.

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

PubMed

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

2013-06-01

This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nuclide Depletion Capabilities in the Shift Monte Carlo Code

DOE PAGES

Davidson, Gregory G.; Pandya, Tara M.; Johnson, Seth R.; ...

2017-12-21

A new depletion capability has been developed in the Exnihilo radiation transport code suite. This capability enables massively parallel domain-decomposed coupling between the Shift continuous-energy Monte Carlo solver and the nuclide depletion solvers in ORIGEN to perform high-performance Monte Carlo depletion calculations. This paper describes this new depletion capability and discusses its various features, including a multi-level parallel decomposition, high-order transport-depletion coupling, and energy-integrated power renormalization. Several test problems are presented to validate the new capability against other Monte Carlo depletion codes, and the parallel performance of the new capability is analyzed.

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer.

PubMed

Mo, Lijun; Chen, Qianmei; Zhang, Xinji; Shi, Xiaojun; Wei, Lili; Zheng, Dianpeng; Li, Hongwei; Gao, Jimin; Li, Jinlong; Hu, Zhiming

2017-10-13

ICOS + Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS + Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects. Our results demonstrated that SA-mGM-CSF vaccine was prepared successfully and tumor growth was inhibited. The tumor size in the combination group was much smaller than that in the vaccine with IgG mAb group. The portions of dendritic cells, CD8 + and CD4 + T cells in the mice blood and tumor tissues were increased after treatment with vaccine. There were more immune-suppressing Tregs infiltrated into tumor after treatment with tumor cell vaccine, and ICOS blocking could deplete the infiltrated Tregs, and T lymphocytes increased more dramatically in the combination therapy group. The concentrations of interferon-γ were increased in all vaccine group, the concentrations of Interleukin-10 and Interleukin-4 were much lower in the combination group. Our study demonstrated that ICOS blocking could deplete the tumor-infiltrated ICOS + Treg cells. Combining GM-CSF surface-modified RM-1 cell vaccine with Anti-ICOS antibody could induce better antitumor immunity than a vaccine alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Matched and Mismatched Metabolic Fuels in Lymphocyte Function

PubMed Central

Caro-Maldonado, Alfredo; Gerriets, Valerie A.; Rathmell, Jeffrey C.

2012-01-01

Immunological function requires metabolic support to suit the needs of lymphocytes at a variety of distinct differentiation and activation states. It is now evident that the signaling pathways that drive lymphocyte survival and activity can directly control cellular metabolism. This linkage provides a mechanism by which activation and specific signaling pathways provide a supply of appropriate and required nutrients to support cell functions in a pro-active supply rather than consumption-based metabolic model. In this way, the metabolism and fuel choices of lymphocytes are guided to specifically match the anticipated needs. If the fuel choice or metabolic pathways of lymphocytes are dysregulated, however, metabolic checkpoints can become activated to disrupt immunological function. These changes are now shown in several immunological diseases and may open new opportunities to selectively enhance or suppress specific immune functions through targeting of glucose, lipid, or amino acid metabolism. PMID:23290889

Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence

PubMed Central

1984-01-01

We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV - specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV - specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence. PMID:6332167

Alterations in T lymphocytes and T-lymphocyte subpopulations in patients with syphilis.

PubMed Central

Jensen, J R; From, E

1982-01-01

The distribution of T-lymphocyte subpopulations was studied in 34 patients with primary or secondary syphilis before and after treatment. An absolute and relative T lymphopenia was found in all patients. In primary syphilis the concentration of helper cells--T cells with Fc receptors for IgM (T mu)--was low whereas in secondary syphilis the suppressor cell concentration--T cells with Fc receptors for IgG (T gamma)--was reduced. Using lymphocytes from healthy subjects this could be imitated in vitro by the addition of serum from patients with secondary syphilis. In many autoimmune diseases a low concentration of T gamma may be a primary factor in the production of autoantibodies. The occurrence of similar changes in patients with secondary syphilis, however, indicates that such fluctuations in the T-cell subpopulations may take place during a strong immune response. PMID:6459815

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

PubMed

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.

Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse

PubMed Central

Hivroz, Claire; Saitakis, Michael

2016-01-01

T lymphocyte activation is a pivotal step of the adaptive immune response. It requires the recognition by T-cell receptors (TCR) of peptides presented in the context of major histocompatibility complex molecules (pMHC) present at the surface of antigen-presenting cells (APCs). T lymphocyte activation also involves engagement of costimulatory receptors and adhesion molecules recognizing ligands on the APC. Integration of these different signals requires the formation of a specialized dynamic structure: the immune synapse. While the biochemical and molecular aspects of this cell–cell communication have been extensively studied, its mechanical features have only recently been addressed. Yet, the immune synapse is also the place of exchange of mechanical signals. Receptors engaged on the T lymphocyte surface are submitted to many tensile and traction forces. These forces are generated by various phenomena: membrane undulation/protrusion/retraction, cell mobility or spreading, and dynamic remodeling of the actomyosin cytoskeleton inside the T lymphocyte. Moreover, the TCR can both induce force development, following triggering, and sense and convert forces into biochemical signals, as a bona fide mechanotransducer. Other costimulatory molecules, such as LFA-1, engaged during immune synapse formation, also display these features. Moreover, T lymphocytes themselves are mechanosensitive, since substrate stiffness can modulate their response. In this review, we will summarize recent studies from a biophysical perspective to explain how mechanical cues can affect T lymphocyte activation. We will particularly discuss how forces are generated during immune synapse formation; how these forces affect various aspects of T lymphocyte biology; and what are the key features of T lymphocyte response to stiffness. PMID:26913033

Decreased membrane potassium permeability and transport in human chronic leukemic and tonsillar lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Segel, G.B.; Lichtman, M.A.

Human blood T-lymphocytes increase their potassium (K/sup +/) permeability and active K/sup +/ transport following lectin or antigen stimulation. We have studied the permeability and active transport of K/sup +/ by lymphocytes in chronic lymphocytic leukemia (CLL) to determine if their membrane K/sup +/ transport was similar to resting or lectin-stimulated normal blood lymphocytes. K/sup +/ transport was assessed both by the rate of isotopic /sup 42/K/sup +/ uptake and by the rate of change in cell K/sup +/ concentration after inhibition of the K/sup +/ transport system with ouabain. CLL lymphocytes had a marked decrease in membrane K/sup +/more » permeability and active transport of K/sup +/ when compared to blood T lymphocytes. K/sup +/ transport in five subjects with CLL (10 mmol . 1 cell water/sup -1/ . h/sup -1/) was half that in normal blood T-lymphocytes (20 mmol . 1 cell water/sup -1/ h/sup -1/). Phytohemagglutinin (PHA) treatment of CLL lymphocytes did not increase significantly their active K/sup +/ transport, whereas K/sup +/ transport by normal T-lymphocytes increased by 100%. Since there were 73% T-lymphocytes in normal blood and 14% in CLL blood, the difference in membrane K/sup +/ turnover could be related either to neoplasia or to the proposed B-lymphocyte origin of CLL. We studied human tonsillar lymphocytes which contained a mean of 34% T-cells. In five studies of tonsils, K/sup +/ transport was 14 mmol . 1 cell water/sup -1/ . h/sup -1/ and treatment with PHA increased K/sup +/ transport only 30%. The intermediate values for basal K/sup +/ transport and K/sup +/ transport in response to PHA in tonsillar lymphocytes were consistent with the proportion of T-lymphocytes present. These data sugges t that B-lymphocytes have reduced membrane permeability and active transport of K/sup +/. Thus the marked decrease in CLL lymphocyte membrane K/sup +/ permeability and transport may be a reflection of its presumed B-cell origin, rather than a membrane

Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

PubMed

Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

1985-04-01

We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells

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)

ClinicalTrials.gov

2018-06-27

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

Evaluation of γ-Induced Apoptosis in Human Peripheral Blood Lymphocytes

NASA Astrophysics Data System (ADS)

Baranova, Elena; Boreyko, Alla; Ravnachka, Ivanka; Saveleva, Maria

2010-01-01

Several experiments have been performed to study regularities in the induction of apoptotic cells in human lymphocytes by 60Co γ-rays at different times after irradiation. Apoptosis induction by 60Co γ-rays in human lymphocytes in different cell cycle phases (G0, S, G1, and G2) has been studied. The maximal apoptosis output in lymphocyte cells was observed in the S phase. Modifying effect of replicative and reparative DNA synthesis inhibitors—1- β -D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (Hu)—on the kinetics of 60Co γ-rays induced apoptosis in human lymphocytes has been studied.

Long-term groundwater depletion in the United States

USGS Publications Warehouse

Konikow, Leonard F.

2015-01-01

The volume of groundwater stored in the subsurface in the United States decreased by almost 1000 km3 during 1900–2008. The aquifer systems with the three largest volumes of storage depletion include the High Plains aquifer, the Mississippi Embayment section of the Gulf Coastal Plain aquifer system, and the Central Valley of California. Depletion rates accelerated during 1945–1960, averaging 13.6 km3/year during the last half of the century, and after 2000 increased again to about 24 km3/year. Depletion intensity is a new parameter, introduced here, to provide a more consistent basis for comparing storage depletion problems among various aquifers by factoring in time and areal extent of the aquifer. During 2001–2008, the Central Valley of California had the largest depletion intensity. Groundwater depletion in the United States can explain 1.4% of observed sea-level rise during the 108-year study period and 2.1% during 2001–2008. Groundwater depletion must be confronted on local and regional scales to help reduce demand (primarily in irrigated agriculture) and/or increase supply.

Lymphocytic colitis complicated by a mass in the terminal ileum.

PubMed

Hui, Chee-Kin

2015-05-01

Lymphocytic colitis is a chronic inflammatory disease affecting the bowel. The clinical course of lymphocytic colitis is believed to be benign with watery diarrhoea. We report herein what is, to the best of our knowledge, the first case of lymphocytic colitis complicated by a terminal ileal mass. A 23-year-old man presented with diarrhoea. Blind biopsies of samples taken from the terminal ileum, caecum and ascending colon showed features of lymphocytic colitis. He declined treatment with budesonide or 5-aminosalicylates. He presented 14 months later with pain over the right lumbar region and nausea. Computed tomographic enteroclysis showed a focal soft tissue enhancing mass at the terminal ileum. Excision of the soft tissue mass revealed that it was reactive nodular lymphoid hyperplasia with fibrous granulation tissue. In conclusion, an untreated lymphocytic colitis may result in the formation of an inflammatory mass lesion.

Lymphocytic hypophysitis in a dog with diabetes insipidus.

PubMed

Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J

2012-11-01

An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polar stratospheric clouds and ozone depletion

NASA Technical Reports Server (NTRS)

Toon, Owen B.; Turco, Richard P.

1991-01-01

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

Brief mindfulness induction could reduce aggression after depletion.

PubMed

Yusainy, Cleoputri; Lawrence, Claire

2015-05-01

Many experiments have shown that one's ability to refrain from acting on aggressive impulses is likely to decrease following a prior act of self-control. This temporary state of self-control failure is known as ego-depletion. Although mindfulness is increasingly used to treat and manage aggressive behaviour, the extent to which mindfulness may counteract the depletion effect on aggression is yet to be determined. This study (N=110) investigated the effect of a laboratory induced one-time mindfulness meditation session on aggression following depletion. Aggression was assessed by the intensity of aversive noise blast participants delivered to an opponent on a computerised task. Depleted participants who received mindfulness induction behaved less aggressively than depleted participants with no mindfulness induction. Mindfulness also improved performance on a second measure of self-control (i.e., handgrip perseverance); however, this effect was independent of depletion condition. Motivational factors may help explain the dynamics of mindfulness, self-control, and aggression. Copyright © 2014 Elsevier Inc. All rights reserved.

Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus and in vitro properties.

PubMed

Anderson, J; Byrne, J A; Schreiber, R; Patterson, S; Oldstone, M B

1985-02-01

We have generated lymphocytic choriomeningitis virus-specific, H-2-restricted cytotoxic thymus-derived lymphocyte (CTL) clones. By using these reagents in several in vitro assays with infected target cells, we show that CTLs by themselves prevent the release of infectious virus into culture fluids and significantly lower the titers of infectious virus previously produced. This ability of cloned CTLs is not influenced by monensin. However, monensin does abrogate the ability of CTLs from spleens of mice primed 6 to 8 days previously with virus to kill virus-infected syngeneic targets. When tested for the participation of lymphokines in this system, the CTLs proliferate when reacted with syngeneic lymphocytic choriomeningitis virus-infected macrophages but fail to make interleukin-2. These CTLs make gamma interferon when reacted with syngeneic virus-infected targets. However, the production of interferon does not directly correlate with CTL-mediated killing. The number of H-2K and D molecules expressed on the target cell surface is not altered during the course of lymphocytic choriomeningitis virus infection. Electron microscopy shows finger-like projections of the CTL clone thrust into the infected cell and lesions bearing an internal diameter of approximately 15 nm in those membranes, illustrating the lytic process.

Effects of cobalt and chromium ions on lymphocyte migration.

PubMed

Baskey, Stephen J; Lehoux, Eric A; Catelas, Isabelle

2017-04-01

A T cell-mediated hypersensitivity reaction has been reported in some patients with CoCrMo-based implants. However, the role of cobalt and chromium ions in this reaction remains unclear. The objective of the present study was to analyze the effects of Co 2+ and Cr 3+ in culture medium, as well as the effects of culture supernatants of macrophages exposed to Co 2+ or Cr 3+ , on the migration of lymphocytes. The release of cytokines/chemokines by macrophages exposed to Co 2+ and Cr 3+ was also analyzed. The migration of murine lymphocytes was quantified using the Boyden chamber assay and flow cytometry, while cytokine/chemokine release by J774A.1 macrophages was measured by ELISA. Results showed an ion concentration-dependent increase in TNF-α and MIP-1α release and a decrease in MCP-1 and RANTES release. Migration analysis showed that the presence of Co 2+ (8 ppm) and Cr 3+ (100 ppm) in culture medium increased the migration of T lymphocytes, while it had little or no effect on the migration of B lymphocytes, suggesting that Co 2+ and Cr 3+ can stimulate the migration of T but not B lymphocytes. Levels of T lymphocyte migration in culture medium containing Co 2+ or Cr 3+ were not statistically different from those in culture supernatants of macrophages exposed to Co 2+ or Cr 3+ , suggesting that the effects of the ions and chemokines were not additive, possibly because of ion interference with the chemokines and/or their cognate receptors. Overall, results suggest that Co 2+ and Cr 3+ are capable of stimulating the migration of T (but not B) lymphocytes in the absence of cytokines/chemokines, and could thereby contribute to the accumulation of more T than B lymphocytes in periprosthetic tissues of some patients with CoCrMo-based implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:916-924, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Lymphocyte responses to stress in postpartum women: relationship to vagal tone.

PubMed

Redwine, L S; Altemus, M; Leong, Y M; Carter, C S

2001-04-01

Although women spend their lives in various phases of the reproductive cycle, including menstrual, pregnancy, postpartum, lactation and menopause, few studies have examined immune responses to stress in women as a function of events associated with reproduction. The objective of this study was to evaluate differential effects of breastfeeding (n = 16), bottlefeeding (n = 10) and non-postpartum (n = 10) status on lymphocyte responses to stressful tasks (public speaking and mental arithmetic). To measure cellular immune responses, lymphocyte proliferation to plant lectins, poke weed mitogen (PWM) and phytohemagglutinin (PHA) were used. The autonomic measures, heart rate, vagal tone, blood pressure and the hormones of the HPA axis, ACTH and cortisol, were measured and their possible roles in mediating lymphocyte proliferation responses were examined. Recently parturient women who were breastfeeding or bottlefeeding had attenuated stress-induced change in lymphocyte responses to PWM compared with non-postpartum women, tested in the follicular phase of their cycle (P < 0.05). Also, lymphocyte responses to PHA were higher in the breastfeeding group compared with non-postpartum controls (P < 0.05). Regression analyses revealed that an index of cardiac vagal tone, but not other autonomic or endocrine measures, was positively predictive of lymphocyte proliferation to PWM. To summarize, these findings suggest that lactation and parturition can influence lymphocyte proliferation and that activity in the vagal system may influence lymphocyte responses to stress.

Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats.

PubMed

Laplante, François; Zhang, Zi-Wei; Huppé-Gourgues, Frédéric; Dufresne, Marc M; Vaucher, Elvire; Sullivan, Ron M

2012-11-01

In rats, selective depletion of the cholinergic interneurons in the ventral striatum (nucleus accumbens or N.Acc.) results in heightened behavioural sensitivity to amphetamine and impaired sensorimotor gating processes, suggesting a hyper-responsiveness to dopamine (DA) activity in the N.Acc. We hypothesized that local cholinergic depletion may also trigger distal functional alterations, particularly in prefrontal cortex (PFC). Adult male Sprague-Dawley rats were injected bilaterally in the N.Acc. with an immunotoxin targeting choline acetyltransferase. Two weeks later, cognitive function was assessed using the delayed alternation paradigm in the T-maze. The rats were then implanted with voltammetric recording electrodes in the ventromedial PFC to measure in vivo extracellular DA release in response to mild tail pinch stress. The PFC was also examined for density of tyrosine hydroxylase (TH)-labelled varicosities. In another cohort of control and lesioned rats, we measured post mortem tissue content of DA. Depletion of cholinergic neurons (restricted to N.Acc.) significantly impaired delayed alternation performance across delay intervals. While (basal) post mortem indices of PFC DA function were unaffected by N.Acc. lesions, in vivo mesocortical DA activation was markedly reduced; this deficit correlated significantly with cognitive impairments. TH-labelled varicosities however, were unaffected in cortical layer V relative to controls. These data suggest that selective depletion of cholinergic interneurons in N.Acc. triggers widespread functional impairments in mesocorticolimbic DA function and cognition. The possible relevance of these findings is also discussed in relation to schizophrenia, where reduced density of cholinergic neurons in ventral striatum has been reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of serotonin in personality inference: tryptophan depletion impairs the identification of neuroticism in the face.

PubMed

Ward, Robert; Sreenivas, Shubha; Read, Judi; Saunders, Kate E A; Rogers, Robert D

2017-07-01

Serotonergic mechanisms mediate the expression of personality traits (such as impulsivity, aggression and anxiety) that are linked to vulnerability to psychological illnesses, and modulate the identification of emotional expressions in the face as well as learning about broader classes of appetitive and aversive signals. Faces with neutral expressions signal a variety of socially relevant information, such that inferences about the big five personality traits, including Neuroticism, Extraversion and Agreeableness, can be accurately made on the basis of emotionally neutral facial photographs. Given the close link between Neuroticism and psychological distress, we investigated the effects of diminished central serotonin activity (achieved by tryptophan depletion) upon the accuracy of 52 healthy (non-clinical) adults' discriminations of personality from facial characteristics. All participants were able to discriminate reliably four of the big five traits. However, the tryptophan-depleted participants were specifically less accurate in discriminating Neuroticism than the matched non-depleted participants. These data suggest that central serotonin activity modulates the identification of not only negative facial emotional expression but also a broader class of signals about personality characteristics linked to psychological distress.

Further characterization of the circulating cell in chronic lymphocytic leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schutz, E.F.; Davis, S.; Rubin, A.D.

Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA-stimulated normal cultures appeared at 2-3 days, CLL cultures required 5-7 days to develop their maximal response, which was 50 percent-60 percent of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin-treated cells produced a normal 72-hr maximal response, no matter whatmore » proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2-3 days. Nylon fiber-adherent lymphocytes consisting of 85 percent immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (ig-bearing) as well as non-fiber-adherent (sheep erythrocyte-rosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5 percent of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.« less

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.

26 CFR 52.4682-1 - Ozone-depleting chemicals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section 4681...

26 CFR 52.4682-1 - Ozone-depleting chemicals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section 4681...

26 CFR 52.4682-1 - Ozone-depleting chemicals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section 4681...

26 CFR 52.4682-1 - Ozone-depleting chemicals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Ozone-depleting chemicals. 52.4682-1 Section 52... EXCISE TAXES (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-1 Ozone-depleting chemicals. (a) Overview. This section provides rules relating to the tax imposed on ozone-depleting chemicals (ODCs) under section 4681...

Possible ozone depletions following nuclear explosions

NASA Technical Reports Server (NTRS)

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

1975-01-01

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

Regret causes ego-depletion and finding benefits in the regrettable events alleviates ego-depletion.

PubMed

Gao, Hongmei; Zhang, Yan; Wang, Fang; Xu, Yan; Hong, Ying-Yi; Jiang, Jiang

2014-01-01

This study tested the hypotheses that experiencing regret would result in ego-depletion, while finding benefits (i.e., "silver linings") in the regret-eliciting events counteracted the ego-depletion effect. Using a modified gambling paradigm (Experiments 1, 2, and 4) and a retrospective method (Experiments 3 and 5), five experiments were conducted to induce regret. Results revealed that experiencing regret undermined performance on subsequent tasks, including a paper-and-pencil calculation task (Experiment 1), a Stroop task (Experiment 2), and a mental arithmetic task (Experiment 3). Furthermore, finding benefits in the regret-eliciting events improved subsequent performance (Experiments 4 and 5), and this improvement was mediated by participants' perceived vitality (Experiment 4). This study extended the depletion model of self-regulation by considering emotions with self-conscious components (in our case, regret). Moreover, it provided a comprehensive understanding of how people felt and performed after experiencing regret and after finding benefits in the events that caused the regret.

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation

PubMed Central

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Background: Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. Materials and Methods: In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. Results: In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. Conclusion: This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications. PMID:25337532

A definition of depletion of fish stocks

USGS Publications Warehouse

Van Oosten, John

1949-01-01

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

Prevalence and cumulative 5-year incidence of chronic lymphocytic leukemia in the adult population in the Russian Federation and Ukraine: Data from the LEUKOSPECT study.

PubMed

Vasylyev, Averyan; Loginov, Alexander; Molostvova, Valentina; Rebrov, Boris; Pereira, Marcelo Horacio S; Melo, Caroline Wirtzbiki A; Makarova, Janina; Pashanov, Evgeny D; Mysnik, Andriy

2017-01-01

LEUKOSPECT was a retrospective, multicenter, epidemiologic study carried out in Russia and Ukraine, aiming to assess the prevalence and cumulative 5-year incidence of chronic lymphocytic leukemia (CLL) in the adult population. All data were collected manually from patient medical records at each of the study sites and from official censuses. CLL prevalence and incidence were determined from a count of CLL cases (previously diagnosed and new cases) in the population who made at least one clinic visit for CLL during the period from 1 January 2009 to 31 December 2013. The recorded cumulative 5-year incidence of CLL during the study ranged from 1.46 per 100 000 persons (95% CI: 0.85-2.34) in Yekaterinburg, Russia, to 4.34 per 100 000 persons (95% CI: 2.48-7.04) in Luhansk, Ukraine. In 2013, the lowest prevalence of CLL was also recorded in Yekaterinburg: 7.11 per 100 000 persons (95% CI: 5.67-8.81). This was approximately 3.1 times lower than in Luhansk (21.92 per 100 000 population; 95% CI: 17.38-27.28). The results of this study show diverse CLL incidence and prevalence patterns in the adult population of the Russian Federation and Ukraine. Authors propose a more comprehensive study with large region involvement to provide a more precise description of the incidence and prevalence of CLL in Eastern European countries and to better understand disparities reported versus the USA and other Western countries.

Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity.

PubMed

Okada, Kazushi; Fukui, Masayuki; Zhu, Bao-Ting

2016-08-26

Glutathione depletion is a distinct cause underlying many forms of pathogenesis associated with oxidative stress and cytotoxicity. Earlier studies showed that glutamate-induced glutathione depletion in immortalized murine HT22 hippocampal neuronal cells leads to accumulation of reactive oxygen species (ROS) and ultimately cell death, but the precise mechanism underlying these processes is not clear. Here we show that during the induction of glutathione depletion, nitric oxide (NO) accumulation precedes ROS accumulation. While neuronal NO synthase (nNOS) in untreated HT22 cells exists mostly as a monomer, glutathione depletion results in increased formation of the dimer nNOS, accompanied by increases in the catalytic activity. We identified that nNOS dimerization is catalyzed by protein disulfide isomerase (PDI). Inhibition of PDI's isomerase activity effectively abrogates glutathione depletion-induced conversion of monomer nNOS into dimer nNOS, accumulation of NO and ROS, and cytotoxicity. Furthermore, we found that PDI is present in untreated cells in an inactive S-nitrosylated form, which becomes activated following glutathione depletion via S-denitrosylation. These results reveal a novel role for PDI in mediating glutathione depletion-induced oxidative cytotoxicity, as well as its role as a valuable therapeutic target for protection against oxidative cytotoxicity. Copyright © 2016. Published by Elsevier Inc.

Nature gives us strength: exposure to nature counteracts ego-depletion.

PubMed

Chow, Jason T; Lau, Shun

2015-01-01

Previous research rarely investigated the role of physical environment in counteracting ego-depletion. In the present research, we hypothesized that exposure to natural environment counteracts ego-depletion. Three experiments were conducted to test this hypothesis. In Experiment 1, initially depleted participants who viewed pictures of nature scenes showed greater persistence on a subsequent anagram task than those who were given a rest period. Experiment 2 expanded upon this finding by showing that natural environment enhanced logical reasoning performance after ego-depleting task. Experiment 3 adopted a two- (depletion vs. no-depletion) -by-two (nature exposure vs. urban exposure) factorial design. We found that nature exposure moderated the effect of depletion on anagram task performance. Taken together, the present studies offer a viable and novel strategy to mitigate the negative impacts of ego-depletion.

Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, George, E-mail: Georg.Klein@ki.se; Klein, Eva; Kashuba, Elena

Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore asmore » a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction

PubMed Central

Yasen, Aizezi; Herrera, Rossana; Rosbe, Kristina

2017-01-01

Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles. Intraepithelial HIV-1 remained infectious for 9 days without viral release. Release of sequestered intraepithelial HIV-1 was induced by the calcium ionophore ionomycin and by cytochalasin D, which increase intracellular calcium and disrupt the cortical actin of epithelial cells, respectively. Cocultivation of epithelial cells containing HIV-1 with activated peripheral blood mononuclear cells and CD4+ T lymphocytes led to the disruption of epithelial cortical actin and spread of virus from epithelial cells to lymphocytes. Treatment of epithelial cells with proinflammatory cytokines tumor necrosis factor-alpha and interferon gamma also induced reorganization of cortical actin and release of virus. Inhibition of MVB formation by small interfering RNA (siRNA)-mediated silencing of its critical protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced viral sequestration in epithelial cells and its transmission from epithelial cells to lymphocytes by ~60–70%. Furthermore, inhibition of vacuole formation of epithelial cells by siRNA-inactivated rabankyrin-5 expression also significantly reduced HIV-1 sequestration in epithelial cells and spread of virus from epithelial cells to lymphocytes. Interaction of the intercellular adhesion molecule-1 of epithelial cells with the function-associated antigen-1

The choline-depleted type II pneumonocyte. A model for investigating the synthesis of surfactant lipids.

PubMed Central

Anceschi, M M; Di Renzo, G C; Venincasa, M D; Bleasdale, J E

1984-01-01

When type II pneumonocytes from adult rats were maintained in a medium that lacked choline, the incorporation of [14C]glycerol into phosphatidylcholine was not greatly diminished during the period that the cells displayed characteristics of type II pneumonocytes. Cells that were maintained in choline-free medium that contained choline oxidase and catalase, however, became depleted of choline and subsequent synthesis of phosphatidylcholine by these cells was responsive to choline in the extracellular medium. Incorporation of [14C]glycerol into phosphatidylcholine by choline-depleted cells was stimulated maximally (approx. 6-fold) by extracellular choline at a concentration (0.05 mM) that also supported the greatest incorporation into phosphatidylglycerol. The incorporation of [14C]glycerol into other glycerophospholipids by choline-depleted cells was not increased by extracellular choline. When cells were incubated in the presence of [3H]cytidine, the choline-dependent stimulation of the synthesis of phosphatidylcholine and phosphatidylglycerol was accompanied by an increased recovery of [3H]CMP. This increased recovery of [3H]CMP reflected an increase in the intracellular amount of CMP from 48 +/- 9 to 76 +/- 16 pmol/10(6) cells. Choline-depleted cells that were exposed to [3H]choline contained [3H]CDP-choline as the principal water-soluble choline derivative. As the extracellular concentration of choline was increase, however, the amount of 3H in phosphocholine greatly exceeded that in all other water-soluble derivatives. Choline-depletion of cells resulted in an increase in the specific activity of CTP:phosphocholine cytidylyltransferase in cell homogenates (from 0.40 +/- 0.15 to 1.31 +/- 0.20 nmol X min-1 X mg of protein-1). These data are indicative that the biosynthesis of phosphatidylcholine is integrated with that of phosphatidylglycerol and are consistent with the proposed involvement of CMP in this integration. The choline-depleted type II pneumonocyte

Lymphocyte count as a sign of immunoparalysis and its correlation with nutritional status in pediatric intensive care patients with sepsis: A pilot study

PubMed Central

Manzoli, Talita Freitas; Delgado, Artur Figueiredo; Troster, Eduardo Juan; de Carvalho, Werther Brunow; Antunes, Ana Caroline Barreto; Marques, Desirée Mayara; Zamberlan, Patrícia

2016-01-01

OBJECTIVES: Developing malnutrition during hospitalization is well recognized worldwide, and children are at a relatively higher risk for malnutrition than adults. Malnutrition can lead to immune dysfunction, which is associated with a higher mortality rate due to sepsis, the most frequent cause of death in pediatric intensive care units (PICUs). The aim of this study was to investigate whether malnourished patients are more likely to have relative or absolute lymphopenia and, consequently, worse prognoses. METHODS: We enrolled 14 consecutive patients with sepsis whose legal representatives provided written informed consent. Patients were classified as normal or malnourished based on anthropometric measurements. As an additional evaluation of nutritional status, serum albumin and zinc were measured on the 1st and 7th days of hospitalization. Lymphocyte count was also measured on the 1st and 7th days. Clinicaltrials.gov: NCT02698683. RESULTS: Malnutrition prevalence rates were 33.3% and 42.8% based on weight and height, respectively. Laboratory analyses revealed a reduction of serum albumin in 100% of patients and reduction of zinc in 93.3% of patients. A total of 35% of patients had fewer than 500 lymphocytes/mm3 on their first day in the PICU. Lymphocyte counts and zinc concentrations significantly increased during hospitalization. CONCLUSIONS: Nutritional evaluations, including anthropometric measurements, were not correlated with lymphocyte counts. Lymphocyte counts concomitantly increased with zinc levels, suggesting that micronutrient supplementation benefits patients with sepsis. PMID:27982165

Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

PubMed Central

Rådestad, E.; Wikell, H.; Engström, M.; Watz, E.; Sundberg, B.; Thunberg, S.; Uzunel, M.; Mattsson, J.; Uhlin, M.

2014-01-01

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study. PMID:25371909

A Case of Complete and Durable Molecular Remission of Chronic Lymphocytic Leukemia Following Treatment with Epigallocatechin-3-gallate, an Extract of Green Tea

PubMed Central

Block, Keith I; Kressel, Bruce R; Sukhatme, Vikas P; White, Jeffrey D

2015-01-01

We report the case of a 48-year-old man who achieved a complete molecular remission 20 years after a diagnosis of chronic lymphocytic leukemia while using epigallicatechin-3-gallate, an extract of green tea. The patient presented at age 28 with lymphocytosis, mild anemia, mild thrombocytopenia, and massive splenomegaly, for which a splenectomy was performed. He was then followed expectantly. Over the next two decades, he suffered two symptomatic chronic lymphocytic leukemia-related events. The first occurred twelve years after diagnosis (at age 40) when the patient developed fevers, night sweats, and moderate anemia. He was diagnosed with autoimmune hemolytic anemia secondary to chronic lymphocytic leukemia. The patient declined conventional therapy in favor of a diet, exercise, and supplement regimen, and recovered from the autoimmune hemolytic anemia though the underlying chronic lymphocytic leukemia remained evident. This is the first published case report of "spontaneous" recovery from secondary autoimmune hemolytic anemia in an adult.  Over the second decade following chronic lymphocytic leukemia diagnosis, serial bone marrow biopsies demonstrated increasing lymphocytosis, with minimal peripheral lymphocytosis. However, twenty years after diagnosis, peripheral lymphocytosis accelerated, with white blood cell counts rising to 55,000/µL. Because the patient continued to refuse conventional therapy, he was treated instead with a supplement regimen that included high doses of epigallocatechin-3-gallate, a green tea extract. Peripheral lymphocytosis resolved. More remarkably, a bone marrow examination, including flow cytometry, showed no evidence of a malignant clone. Two years later (at age 51), the peripheral blood and bone marrow were without molecular evidence of chronic lymphocytic leukemia or any malignancy. The patient remains well at age 52.  PMID:26858922

Acute lymphocytic cholangitis and liver failure in an Amur tiger (Panthera tigris altaica).

PubMed

Crook, Erika K; Carpenter, Nancy A

2014-03-01

An adult male Amur tiger (Panthera tigris altaica) with confirmed inflammatory bowel disease developed acute severe icterus, bilirubinuria, bilirubinemia, and elevated bile acids after a diet change. Liver biopsies showed moderate lymphoplasmacytic cholangiohepatitis (lymphocytic cholangitis). The tiger developed neurologic signs including ataxia, tremors, and seizures, as well as epistaxis. Therapy consisted of antibiotics, a steroid anti-inflammatory, vitamins, pro-coagulants, and liver-supportive medicines. The tiger improved from acute liver failure within 3 wk, while the epistaxis began at 3.5 wk and did not resolve until 10.5 wk. The long-term maintenance plan consists of oral prednisolone, metronidazole, ursodiol, and an all muscle-meat beef diet.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

PubMed Central

Laksono, Brigitta M.; Grosserichter-Wagener, Christina; de Vries, Rory D.; Langeveld, Simone A. G.; Brem, Maarten D.; van Dongen, Jacques J. M.; Koopmans, Marion P. G.

2018-01-01

ABSTRACT Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing

Carrier detection of pyruvate carboxylase deficiency in fibroblasts and lymphocytes.

PubMed

Atkin, B M

1979-10-01

Pyruvate carboxylase (E.C. 6.4.1.1) activity was determined in the circulating peripheral lymphocytes and cultured skin fibroblasts from the family of a patient with hepatic, cerebral, renal cortical, leukocyte, and fibroblast pyruvate carboxylase deficiency (PC Portland deficiency). Lymphocyte activities were: mother, 33--39%; father, 11--29%; brother, 82--103%; and sister, 38--48% of the lowest normal. Fibroblasts from the patient's mother and father had 42 and 34%, respectively, of the activity of the lowest normal. These data demonstrate that the disease is inherited in an autosomal recessive manner and that lymphocytes and fibroblasts can be used to detect carriers. Neither pyruvate carboxylase nor mitochondrial PEPCK activity in lymphocytes was increased by a 21-hr fast.

ELEMENTAL DEPLETIONS IN THE MAGELLANIC CLOUDS AND THE EVOLUTION OF DEPLETIONS WITH METALLICITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tchernyshyov, Kirill; Meixner, Margaret; Seale, Jonathan

2015-10-01

We present a study of the composition of gas and dust in the Large and Small Magellanic Clouds (LMC and SMC) using UV absorption spectroscopy. We measure P ii and Fe ii along 84 spatially distributed sightlines toward the MCs using archival Far Ultraviolet Spectroscopic Explorer observations. For 16 of those sightlines, we also measure Si ii, Cr ii, and Zn ii from new Hubble Space Telescope Cosmic Origins Spectrograph observations. We analyze these spectra using a new spectral line analysis technique based on a semi-parametric Voigt profile model. We have combined these measurements with H i and H{sub 2}more » column densities and reference stellar abundances from the literature to derive gas-phase abundances, depletions, and gas-to-dust ratios (GDRs). Of our 84 P and 16 Zn measurements, 80 and 13, respectively, are depleted by more than 0.1 dex, suggesting that P and Zn abundances are not accurate metallicity indicators at and above the metallicity of the SMC. Si, Cr, and Fe are systematically less depleted in the SMC than in the Milky Way (MW) or LMC. The minimum Si depletion in the SMC is consistent with zero. We find GDR ranges of 190–565 in the LMC and 480–2100 in the SMC, which is broadly consistent with GDRs from the literature. These ranges represent actual location to location variation and are evidence of dust destruction and/or growth in the diffuse neutral phase of the interstellar medium. Where they overlap in metallicity, the gas-phase abundances of the MW, LMC, and SMC and damped Lyα systems evolve similarly with metallicity.« less

How Ego Depletion Affects Sexual Self-Regulation: Is It More Than Resource Depletion?

PubMed

Nolet, Kevin; Rouleau, Joanne-Lucine; Benbouriche, Massil; Carrier Emond, Fannie; Renaud, Patrice

2015-12-21

Rational thinking and decision making are impacted when in a state of sexual arousal. The inability to self-regulate arousal can be linked to numerous problems, like sexual risk taking, infidelity, and sexual coercion. Studies have shown that most men are able to exert voluntary control over their sexual excitation with various levels of success. Both situational and dispositional factors can influence self-regulation achievement. The goal of this research was to investigate how ego depletion, a state of low self-control capacity, interacts with personality traits-propensities for sexual excitation and inhibition-and cognitive absorption, to cause sexual self-regulation failure. The sexual responses of 36 heterosexual males were assessed using penile plethysmography. They were asked to control their sexual arousal in two conditions, with and without ego depletion. Results suggest that ego depletion has opposite effects based on the trait sexual inhibition, as individuals moderately inhibited showed an increase in performance while highly inhibited ones showed a decrease. These results challenge the limited resource model of self-regulation and point to the importance of considering how people adapt to acute and high challenging conditions.

Relationship between the ability of sunscreens containing 2-ethylhexyl-4'-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo.

PubMed

Walker, S L; Morris, J; Chu, A C; Young, A R

1994-01-01

The UVB sunscreen 2-ethylhexyl-4'-methoxycinnamate was evaluated in hairless albino mouse skin for its ability to inhibit UVR-induced (i) oedema, (ii) epidermal Langerhans cell (Ia+) depletion and (iii) suppression of the alloactivating capacity of epidermal cells (mixed epidermal cell-lymphocyte reaction, MECLR). The sunscreen, prepared at 9% in ethanol or a cosmetic lotion, was applied prior to UVB/UVA irradiation. In some experiments there was a second application halfway through the irradiation. Single applications in both vehicles gave varying degrees of protection from oedema and Langerhans cell depletion but afforded no protection from suppression of MECLR. When the sunscreens were applied twice there was improved protection from oedema and Langerhans cell depletion and complete protection was afforded from suppression of MECLR. There was a clear linear relationship between Langerhans cell numbers and oedema with and without sunscreen application. The relationship between Langerhans cell numbers and MECLR was more complex. These data confirm published discrepancies between protection from oedema (a model for human erythema) and endpoints with immunological significance, but show that 2-ethylhexyl-4'-methoxycinnamate can afford complete immunoprotection, although protection is dependent on the application rate and vehicle.

Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes.

PubMed

Petrov, V; Fagard, R; Lijnen, P

2000-05-01

The purpose of these investigations was to determine whether the aminopeptidase B and leucine aminopeptidase inhibitor bestatin, the chymase inhibitor chymostatin, the calpain inhibitor E-64, and the neutral serine protease inhibitor leupeptin affect the angiotensin converting enzyme (ACE) activity in T-lymphocytes. ACE activity in homogenates of T-lymphocytes or in intact T-lymphocytes in suspension was measured by determining fluorimetrically histidyl-leucine, formed from the conversion of hippuryl-histidyl-leucine, coupled with ophtaldialdehyde. The effect of various concentrations (10(-9) to 10(-3) mol/L) of the angiotensin-converting enzyme inhibitors lisinopril and captopril and of the various protease inhibitors on ACE activity was studied. Lisinopril and captopril reduced the ACE activity in homogenates of T-lymphocytes in a concentration-dependent manner. Lisinopril exhibited a more pronounced inhibition of ACE in T-lymphocytes than did captopril. Chymostatin and E-64 had no effect on the ACE activity in T-lymphocytes, whereas leupeptin inhibited its activity in a dose-dependent fashion. Bestatin, on the contrary, increased the ACE activity in homogenates of T-lymphocytes as well as in intact T-lymphocytes in proportion to the concentration. Our data showed that the ACE activity in T-lymphocytes was stimulated by bestatin and inhibited by leupeptin, whereas chymostatin and E-64 did not affect the ACE activity in T-lymphocytes.

The Immunological and Migratory Properties of the Lymphocytes Recirculating Through the Rat Spleen

PubMed Central

Ford, W. L.

1969-01-01

The great majority of the cells released by the isolated, perfused rat spleen were lymphocytes of which about 95 per cent were small lymphocytes. The rate of release of small lymphocytes from the spleen was independent of the prevailing concentration in the perfusate. The cells released by the spleen were immunologically competent in respect of a graft-versus-host reaction and a primary antibody response. They could also transfer secondary responsiveness to a viral antigen. Several spleen donors were given a continuous intravenous infusion of tritiated thymidine prior to spleen perfusion and the proportion of labelled small lymphocytes among the population released by the spleen was compared to the proportion in populations of small lymphocytes from other sources. The small lymphocytes released by the spleen recirculated from the blood to thoracic duct lymph after injection into a syngeneic recipient. Conversely the perfused spleen released thoracic duct small lymphocytes which had been given to the spleen donor 24 hr previously. It is therefore probable that a single population of recirculating small lymphocytes exists which migrates from the blood into both lymph-nodes and spleen. The release of small lymphocytes from the spleen was mostly at the expense of the lymphocyte content of the periarteriolar lymphoid sheaths. ImagesFigs. 8-9Figs. 4-5Fig. 10Figs. 6-7 PMID:5792901

Memory B lymphocytes determine repertoire oligoclonality early after haematopoietic stem cell transplantation

PubMed Central

OMAZIC, B; LUNDKVIST, I; MATTSSON, J; PERMERT, J; NÄSMAN-BJÖRK, I

2003-01-01

The objective of this study was to investigate if oligoclonality of the Ig repertoire post-haematopoietic stem cell transplantation (HSCT) is restricted to memory B lymphocytes or if it is a general property among B lymphocytes. As a measure of B lymphocyte repertoire diversity, we have analysed size distribution of polymerase chain reaction (PCR) amplified Ig H complementarity determining region 3 (CDR3) in naive and memory B lymphocytes isolated from patients before HSCT and at 3, 6 and 12 months after HSCT as well as from healthy controls. We demonstrate a limited variation of the IgH CDR3 repertoire in the memory B lymphocyte population compared to the naive B cell population. This difference was significant at 3 and 6 months post-HSCT. Compared to healthy controls there is a significant restriction of the memory B lymphocyte repertoire at 3 months after HSCT, but not of the naive B lymphocyte repertoire. Twelve months after HSCT, the IgH CDR3 repertoire in both memory and naive B lymphocytes are as diverse as in healthy controls. Thus, our findings suggest a role for memory B cells in the restriction of the oligoclonal B cell repertoire observed early after HSCT, which may be of importance when considering reimmunization of transplanted patients. PMID:12974769

Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease.

PubMed

Braun, David J; Kalinin, Sergey; Feinstein, Douglas L

2017-01-01

Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes to the evolution of neuroinflammation and neurodegeneration in a variety of conditions and diseases. One cause of LC damage may be loss of neurotrophic support from LC target regions. We tested this hypothesis by conditional unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To evaluate the consequences of BDNF loss in the context of neurodegeneration, the mice harbored familial mutations for human amyloid precursor protein and presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion also reduced noradrenergic innervation in the hippocampus, the frontal cortex, and molecular layer of the cerebellum, assessed by staining for dopamine beta hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers and size but was without effect on plaque numbers in the striatum, a site with minimal innervation from the LC. Interestingly, cortical Iba1 staining for microglia was reduced by BDNF depletion and was correlated with reduced dopamine beta hydroxylase staining. These data demonstrate that reduction of BDNF levels in an LC target region can cause retrograde damage to LC neurons, leading to exacerbation of neuropathology in distinct LC target areas. Methods to reduce BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative processes normally limited by LC noradrenergic activities.

Locomotion in Lymphocytes is Altered by Differential PKC Isoform Expression

NASA Technical Reports Server (NTRS)

Sundaresan, A.; Risin, D.; Pellis, N. R.

1999-01-01

Lymphocyte locomotion is critical for proper elicitation of the immune response. Locomotion of immune cells via the interstitium is essential for optimal immune function during wound healing, inflammation and infection. There are conditions which alter lymphocyte locomotion and one of them is spaceflight. Lymphocyte locomotion is severely inhibited in true spaceflight (true microgravity) and in rotating wall vessel culture (modeled microgravity). When lymphocytes are activated prior to culture in modeled microgravity, locomotion is not inhibited and the levels are comparable to those of static cultured lymphocytes. When a phorbol ester (PMA) is used in modeled microgravity, lymphocyte locomotion is restored by 87%. This occurs regardless if PMA is added after culture in the rotating wall vessel or during culture. Inhibition of DNA synthesis also does not alter restoration of lymphocyte locomotion by PMA. PMA is a direct activator of (protein kinase C) PKC . When a calcium ionophore, ionomycin is used it does not possess any restorative properties towards locomotion either alone or collectively with PMA. Since PMA brings about restoration without help from calcium ionophores (ionomycin), it is infer-red that calcium independent PKC isoforms are involved. Changes were perceived in the protein levels of PKC 6 where levels of the protein were downregulated at 24,72 and 96 hours in untreated rotated cultures (modeled microgravity) compared to untreated static (1g) cultures. At 48 hours there is an increase in the levels of PKC & in the same experimental set up. Studies on transcriptional and translational patterns of calcium independent isoforms of PKC such as 8 and E are presented in this study.

Leukemia -- Chronic T-Cell Lymphocytic

MedlinePlus

... 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 ...

Mesospheric ionization and O2 1Delta(g) depletion

NASA Technical Reports Server (NTRS)

Spear, K. A.; Solomon, S.

1987-01-01

Observations of O2 1Delta(g) emission during solar proton events reveal large depletions below 80 and near 90 km. The lower-altitude depletions are believed to be due to odd hydrogen production and associated depletion of ozone, but the mechanism producing the depletion near 90 km has not yet been established. In this paper, it is proposed that an exothermic charge exchange reaction between O2(+) and O2 1Delta(g) is likely to be responsible for these high-altitude depletions. In particular, it is shown that the vertical structure of the observed change in airglow emission is consistent with this mechanism.

VLA-4 antagonists: potent inhibitors of lymphocyte migration.

PubMed

Yang, Ginger X; Hagmann, William K

2003-05-01

Circulating lymphocytes normally migrate through extravascular spaces in relatively low numbers as important members of the immunosurveillance process. That is until signals are received by endothelial cells that there is an underlying infection or inflammatory condition. These vascular surface cells in turn overexpress and present ligands to circulating lymphocyte adhesion molecules. Upon encountering this higher density of ligands, lymphocytes, which had been leisurely rolling along the vascular surface, now become more firmly attached, change shape, and migrate through tight junctions to the sites of infection or inflammation. If the initiating events are not resolved and the condition becomes chronic, there can be a sustained extravasation of lymphocytes that can exacerbate the inflammatory condition, which in turn will continue to recruit more inflammatory cells resulting in unwanted tissue destruction. It is for the attenuation of this cycle of sustained inflammatory cell recruitment that very late activating antigen-4 (VLA-4) antagonists are being developed. Most lymphocytes, except neutrophils, express VLA-4 on their surface and they interact with endothelial vascular cell adhesion molecule-1 (VCAM-1). It is this interaction that VLA-4 antagonists are intended to disrupt, thus, putting an end to the cycle of chronic inflammation, which is the hallmark of many diseases. This review will provide an update of VLA-4 antagonists that have appeared since early 2001 and will discuss some of the issues, both positive and negative, that may be encountered in their development. Copyright 2003 Wiley Periodicals, Inc.

Fully depleted back illuminated CCD

DOEpatents

Holland, Stephen Edward

2001-01-01

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

Ecdysteroid excretion by adult Hymenolepis diminuta in vitro.

PubMed

Mercer, J G; Munn, A E; Arme, C; Rees, H H

1987-12-01

Both patent and prepatent adult Hymenolepis diminuta excreted 20-hydroxyecdysone into the culture medium when maintained in vitro. Patent worms also excreted ecdysone and comparatively large quantities of unidentified immunoreactive material of a relatively apolar nature. This latter material was shown to be depleted from the endogenous free ecdysteroids of patent adults during the culture period. Ecdysteroid excretion was affected both qualitatively and quantitatively when culturing conditions were varied.

Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4{sup +} intestinal intraepithelial lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku

2013-06-14

Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs)more » and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.« less

Signaling in Human and Murine Lymphocytes in Microgravity: Parallels and Contrasts

NASA Technical Reports Server (NTRS)

Neal, Pellis; Alamelu, Sundaresan; Kulkarni, A. D.; Yamauchi, K.

2006-01-01

Immune function in space undergoes dramatic changes, some of which are detrimental to lymphocyte function. These changes may lead to significant immune suppression. Studies with human lymphocytes both in space flight and with ground-based models (NASA in vitro ground-based microgravity analog) indicate that T cell activation is inhibited in microgravity. Other lymphocyte functions, such as locomotion, are also inhibited. There is about an 80 percent homology in the immune response of mice to that of humans. A murine model was investigated because of its ability to parallel some microgravity using hind limb suspension. In in vivo antiorthostatically (AOS)-suspended mice, T cell activation is greatly suppressed, with the majority of activation related cytokines being inhibited. PHA activation in lymphocytes derived from AOS mice (in vivo ground-based microgravity analog) is also suppressed. Calcium ionophore studies in human lymphocytes exposed to modeled microgravity indicate that the calcium pathways are probably unaffected in microgravity. IP3 (inositol triphosphate) receptor expression in both human and mouse lymphocytes cultured in modeled microgravity indicate no suppression of calcium signaling. In the human system, microgravity seems to inhibit signaling cascades either at the level of, or up-stream of, Protein Kinase C (PKC). In particular, a membrane event, such as phospholipase C gamma 1 activity in human lymphocytes is affected, with its direct upstream effector, LAT, being deficiently expressed. In the mouse pathway, LAT is undiminished while another critical intermediate, SLP-76, is diminished significantly. This study identifies critical stages in the human and mouse immune systems and in lymphocytes as a function of microgravity.

Primary lymphocytic lymphoma of lacrimal gland.

PubMed

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.

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

PubMed

Kossard, S; Collins, A; McCrossin, I

1987-05-01

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

ARMS depletion facilitates UV irradiation induced apoptotic cell death in melanoma.

PubMed

Liao, Yi-Hua; Hsu, Su-Ming; Huang, Pei-Hsin

2007-12-15

Tumor cells often aberrantly reexpress molecules that mediate proper embryonic development for advantageous growth or survival. Here, we report that ankyrin repeat-rich membrane spanning (ARMS), a transmembrane protein abundant in the developing and adult neural tissues, is overexpressed in melanoma, a tumor ontogenetically originating from neural crest. Immunohistochemical study of 79 melanocytic lesions showed significantly increased expression of ARMS in primary malignant melanomas (92.9%) and metastatic melanoma (60.0%) in comparison with benign nevocellular nevi (26.7%). To investigate the role of ARMS in melanoma formation, murine B16F0 melanoma cells with stable knockdown of ARMS were established by RNA interference. Down-regulation of ARMS resulted in significant inhibition of anchorage-independent growth in soft agar and restrictive growth of melanoma in severe combined immunodeficient mice. Importantly, depletion of ARMS facilitated UVB-induced apoptosis in melanoma cells through inactivation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK. Addition of MEK inhibitor PD98059 further sensitized ARMS-depleted melanoma cells to UVB-induced apoptosis, whereas constitutively active MEK rescued ARMS-depleted cells from apoptosis. We further showed that BRAF, a downstream signaling molecule of ARMS in ERK pathway, is not mutated as a constitutively active form in acral lentiginous melanoma; in contrast, BRAF(T1799A) mutation, which leads to constitutive activation of ERK signaling, was detected in 57.1% of superficial spreading melanoma. Our study suggests that overexpression of ARMS per se serves as one mechanism to promote melanoma formation by preventing stress-induced apoptotic death mediated by the MEK/ERK signaling pathway, especially in acral lentiginous melanoma, most of which does not harbor BRAF mutation.

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

PubMed

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

PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-12

Classical Hodgkin Lymphoma; Lymphocyte-Depleted Classical Hodgkin Lymphoma; Lymphocyte-Rich Classical Hodgkin Lymphoma; Mixed Cellularity Classical Hodgkin Lymphoma; Nodular Sclerosis Classical Hodgkin Lymphoma

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

PubMed

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.

Groundwater depletion in the United States (1900−2008)

USGS Publications Warehouse

Konikow, Leonard F.

2013-01-01

A natural consequence of groundwater withdrawals is the removal of water from subsurface storage, but the overall rates and magnitude of groundwater depletion in the United States are not well characterized. This study evaluates long-term cumulative depletion volumes in 40 separate aquifers or areas and one land use category in the United States, bringing together information from the literature and from new analyses. Depletion is directly calculated using calibrated groundwater models, analytical approaches, or volumetric budget analyses for multiple aquifer systems. Estimated groundwater depletion in the United States during 1900–2008 totals approximately 1,000 cubic kilometers (km3). Furthermore, the rate of groundwater depletion has increased markedly since about 1950, with maximum rates occurring during the most recent period (2000–2008) when the depletion rate averaged almost 25 km3 per year (compared to 9.2 km3 per year averaged over the 1900–2008 timeframe).

Mesocortical dopamine depletion and anxiety-related behavior in the rat: sex and hemisphere differences.

PubMed

Sullivan, R M; Dufresne, M M; Siontas, D; Chehab, S; Townsend, J; Laplante, F

2014-10-03

The mesocortical dopamine (DA) system of the rat plays an important role in prefrontal cortex (PFC) regulation of stress and emotion and exhibits functional hemispheric asymmetry for such processing. Since few studies examine sex differences in this context, we compared the effects of left vs. right unilateral PFC DA depletion in males and females in several behavioral situations associated with anxiety or aversion. Adult rats received unilateral injections of 6-hydroxydopamine (6-OHDA) or vehicle in the ventromedial (vm) PFC. Behavioral tests included a predator odor burying test, elevated plus maze and sucrose consumption with simple taste aversion. Tissue analysis confirmed that vmPFCs injected with 6-OHDA were depleted of DA (75-85%) compared to controls. Burying behavior and sucrose consumption were affected only by left lesions, similarly in both sexes. However, risk assessment behaviors were affected by right lesions in opposite directions in males and females. Behaviors modified preferentially by the left cortex thus showed less evidence of sex differences than those modulated by the right. While mesocortical DA depletion effects are lateralized, the nature of these effects can vary with sex and specific behavior. Such findings may be clinically significant, given the large gender differences in the incidence of mood and anxiety disorders, which also show many lateralized prefrontal abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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.

PubMed

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.

A Multilab Preregistered Replication of the Ego-Depletion Effect.

PubMed

Hagger, Martin S; Chatzisarantis, Nikos L D; Alberts, Hugo; Anggono, Calvin Octavianus; Batailler, Cédric; Birt, Angela R; Brand, Ralf; Brandt, Mark J; Brewer, Gene; Bruyneel, Sabrina; Calvillo, Dustin P; Campbell, W Keith; Cannon, Peter R; Carlucci, Marianna; Carruth, Nicholas P; Cheung, Tracy; Crowell, Adrienne; De Ridder, Denise T D; Dewitte, Siegfried; Elson, Malte; Evans, Jacqueline R; Fay, Benjamin A; Fennis, Bob M; Finley, Anna; Francis, Zoë; Heise, Elke; Hoemann, Henrik; Inzlicht, Michael; Koole, Sander L; Koppel, Lina; Kroese, Floor; Lange, Florian; Lau, Kevin; Lynch, Bridget P; Martijn, Carolien; Merckelbach, Harald; Mills, Nicole V; Michirev, Alexej; Miyake, Akira; Mosser, Alexandra E; Muise, Megan; Muller, Dominique; Muzi, Milena; Nalis, Dario; Nurwanti, Ratri; Otgaar, Henry; Philipp, Michael C; Primoceri, Pierpaolo; Rentzsch, Katrin; Ringos, Lara; Schlinkert, Caroline; Schmeichel, Brandon J; Schoch, Sarah F; Schrama, Michel; Schütz, Astrid; Stamos, Angelos; Tinghög, Gustav; Ullrich, Johannes; vanDellen, Michelle; Wimbarti, Supra; Wolff, Wanja; Yusainy, Cleoputri; Zerhouni, Oulmann; Zwienenberg, Maria

2016-07-01

Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control. © The Author(s) 2016.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

PubMed Central

Theorell, Jakob; Bileviciute-Ljungar, Indre; Tesi, Bianca; Schlums, Heinrich; Johnsgaard, Mette Sophie; Asadi-Azarbaijani, Babak; Bolle Strand, Elin; Bryceson, Yenan T.

2017-01-01

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients. No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators. In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers

Ego Depletion Does Not Interfere With Working Memory Performance.

PubMed

Singh, Ranjit K; Göritz, Anja S

2018-01-01

Ego depletion happens if exerting self-control reduces a person's capacity to subsequently control themselves. Previous research has suggested that ego depletion not only interferes with subsequent self-control but also with working memory. However, recent meta-analytical evidence casts doubt onto this. The present study tackles the question if ego depletion does interfere with working memory performance. We induced ego depletion in two ways: using an e-crossing task and using a Stroop task. We then measured working memory performance using the letter-number sequencing task. There was no evidence of ego depletion interfering with working memory performance. Several aspects of our study render this null finding highly robust. We had a large and heterogeneous sample of N = 1,385, which provided sufficient power. We deployed established depletion tasks from two task families (e-crossing task and Stroop), thus making it less likely that the null finding is due to a specific depletion paradigm. We derived several performance scores from the working memory task and ran different analyses to maximize the chances of finding an effect. Lastly, we controlled for two potential moderators, the implicit theories about willpower and dispositional self-control capacity, to ensure that a possible effect on working memory is not obscured by an interaction effect. In sum, this experiment strengthens the position that ego depletion works but does not affect working memory performance.

Ego Depletion Does Not Interfere With Working Memory Performance

PubMed Central

Singh, Ranjit K.; Göritz, Anja S.