Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.

PubMed

Uchiyama, M; Jin, X; Zhang, Q; Amano, A; Watanabe, T; Niimi, M

2012-05-01

In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells. Copyright © 2012 Elsevier Inc. All rights reserved.

HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK.

PubMed

El Bouzidi, Kate; White, Ellen; Mbisa, Jean L; Sabin, Caroline A; Phillips, Andrew N; Mackie, Nicola; Pozniak, Anton L; Tostevin, Anna; Pillay, Deenan; Dunn, David T

2016-12-01

Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. We examined darunavir DRMs emerging in clinical practice in the UK. Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

PubMed

Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

2005-03-01

Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

TLR4 signaling in effector CD4+ T cells regulates TCR activation and experimental colitis in mice

PubMed Central

González-Navajas, José M.; Fine, Sean; Law, Jason; Datta, Sandip K.; Nguyen, Kim P.; Yu, Mandy; Corr, Maripat; Katakura, Kyoko; Eckman, Lars; Lee, Jongdae; Raz, Eyal

2010-01-01

TLRs sense various microbial products. Their function has been best characterized in DCs and macrophages, where they act as important mediators of innate immunity. TLR4 is also expressed on CD4+ T cells, but its physiological function on these cells remains unknown. Here, we have shown that TLR4 triggering on CD4+ T cells affects their phenotype and their ability to provoke intestinal inflammation. In a model of spontaneous colitis, Il10–/–Tlr4–/– mice displayed accelerated development of disease, with signs of overt colitis as early as 8 weeks of age, when compared with Il10–/– and Il10–/–Tlr9–/– mice, which did not develop colitis by 8 months. Similar results were obtained in a second model of colitis in which transfer of naive Il10–/–Tlr4–/– CD4+ T cells into Rag1–/– recipients sufficient for both IL-10 and TLR4 induced more aggressive colitis than the transfer of naive Il10–/– CD4+ T cells. Mechanistically, LPS stimulation of TLR4-bearing CD4+ T cells inhibited ERK1/2 activation upon subsequent TCR stimulation via the induction of MAPK phosphatase 3 (MKP-3). Our data therefore reveal a tonic inhibitory role for TLR4 signaling on subsequent TCR-dependent CD4+ T cell responses. PMID:20051628

IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro.

PubMed

Alves, Nuno L; Hooibrink, Berend; Arosa, Fernando A; van Lier, René A W

2003-10-01

Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8+ T cells, it has no apparent function in controlling homeostatic proliferation of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15. In this process, naive CD8+ T cells successively down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with these phenotypic changes, naive cells acquired the ability to produce interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), expressed perforin and granzyme B, and acquired cytotoxic properties. Primed CD8+ T cells, from both noncytotoxic (CD45RA-CD27+) and cytotoxic (CD45RA+CD27-) subsets, responded to IL-15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells. In summary, all human CD8+ T-cell subsets had the ability to respond to IL-15, which suggests a generic influence of this cytokine on CD8+ T-cell homeostasis in man.

Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90.

PubMed

Saha, Banishree; Momen-Heravi, Fatemeh; Furi, Istvan; Kodys, Karen; Catalano, Donna; Gangopadhyay, Anwesha; Haraszti, Reka; Satishchandran, Abhishek; Iracheta-Vellve, Arvin; Adejumo, Adeyinka; Shaffer, Scott A; Szabo, Gyongyi

2018-05-01

A salient feature of alcoholic liver disease (ALD) is Kupffer cell (KC) activation and recruitment of inflammatory monocytes and macrophages (MØs). These key cellular events of ALD pathogenesis may be mediated by extracellular vesicles (EVs). EVs transfer biomaterials, including proteins and microRNAs, and have recently emerged as important effectors of intercellular communication. We hypothesized that circulating EVs from mice with ALD have a protein cargo characteristic of the disease and mediate biological effects by activating immune cells. The total number of circulating EVs was increased in mice with ALD compared to pair-fed controls. Mass spectrometric analysis of circulating EVs revealed a distinct signature for proteins involved in inflammatory responses, cellular development, and cellular movement between ALD EVs and control EVs. We also identified uniquely important proteins in ALD EVs that were not present in control EVs. When ALD EVs were injected intravenously into alcohol-naive mice, we found evidence of uptake of ALD EVs in recipient livers in hepatocytes and MØs. Hepatocytes isolated from mice after transfer of ALD EVs, but not control EVs, showed increased monocyte chemoattractant protein 1 mRNA and protein expression, suggesting a biological effect of ALD EVs. Compared to control EV recipient mice, ALD EV recipient mice had increased numbers of F4/80 hi cluster of differentiation 11b (CD11b) lo KCs and increased percentages of tumor necrosis factor alpha-positive/interleukin 12/23-positive (inflammatory/M1) KCs and infiltrating monocytes (F4/80 int CD11b hi ), while the percentage of CD206 + CD163 + (anti-inflammatory/M2) KCs was decreased. In vitro, ALD EVs increased tumor necrosis factor alpha and interleukin-1β production in MØs and reduced CD163 and CD206 expression. We identified heat shock protein 90 in ALD EVs as the mediator of ALD-EV-induced MØ activation. Our study indicates a specific protein signature of ALD EVs and demonstrates

Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia

PubMed Central

Fujita, Kazutoshi; Ohta, Hiroshi; Tsujimura, Akira; Takao, Tetsuya; Miyagawa, Yasushi; Takada, Shingo; Matsumiya, Kiyomi; Wakayama, Teruhiko; Okuyama, Akihiko

2005-01-01

More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2Kb/H-2Db) and for CD45. Cells that did not stain positively for H-2Kb/H-2Db and CD45 were sorted as the germ cell–enriched fraction. The sorted germ cell–enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia. PMID:15965502

Experimental allergic orchitis in mice. V. Resistance to actively induced disease in BALB/cJ substrain mice is mediated by CD4+ T cells

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

Teuscher, C.; Hickey, W.F.; Korngold, R.

1990-01-01

Previous studies have shown that differential susceptibility to actively induced experimental allergic orchitis (EAO) exists among various BALB/c substrains. Of 13 substrains studied, BALB/cJ mice consistently exhibit greater resistance to disease induction. Such resistance is associated with a single recessive genotypic difference in an immunoregulatory locus which is unlinked to any of the known alleles distinguishing the BALB/cJ substrain. In this study, gene complementation protocols were used to study the genetics of susceptibility and resistance to EAO. The results indicate that resistance in BALB/cJ mice is not due to a mutation in the H-2Dd linked gene which governs the phenotypicmore » expression of autoimmune orchitis. The mechanistic basis for disease resistance was examined using reciprocal bone marrow radiation chimeras generated between the disease-susceptible BALB/cByJ (ByJ) substrain and BALB/cJ (Jax) mice. All constructs, including Jax----Jax and Jax----ByJ, developed severe EAO following inoculation with mouse testicular homogenate (MTH) and adjuvants whereas control chimeras immunized with adjuvants alone did not. These results suggest that an active immunoregulatory mechanism rather than a passive one, such as the lack of T cells and/or B cells with receptors for the aspermatogenic autoantigens relevant in the induction of EAO, is responsible for disease resistance in BALB/cJ mice. The role of immunoregulatory cells was examined by pretreating BALB/cJ mice with either cyclophosphamide (20 mg/kg) or low-dose whole body or total lymphoid irradiation (350 rads) 2 days prior to inoculation. BALB/cJ mice immunized with MTH plus adjuvants generate immunoregulatory spleen cells (SpCs) that, when transferred to naive BALB/cByJ recipients, significantly reduce the severity of autoimmune orchitis observed during actively induced EAO.« less

Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses.

PubMed

Paust, Silke; Gill, Harvinder S; Wang, Bao-Zhong; Flynn, Michael P; Moseman, E Ashley; Senman, Balimkiz; Szczepanik, Marian; Telenti, Amalio; Askenase, Philip W; Compans, Richard W; von Andrian, Ulrich H

2010-12-01

Hepatic natural killer (NK) cells mediate antigen-specific contact hypersensitivity (CHS) in mice deficient in T cells and B cells. We report here that hepatic NK cells, but not splenic or naive NK cells, also developed specific memory of vaccines containing antigens from influenza, vesicular stomatitis virus (VSV) or human immunodeficiency virus type 1 (HIV-1). Adoptive transfer of virus-sensitized NK cells into naive recipient mice enhanced the survival of the mice after lethal challenge with the sensitizing virus but not after lethal challenge with a different virus. NK cell memory of haptens and viruses depended on CXCR6, a chemokine receptor on hepatic NK cells that was required for the persistence of memory NK cells but not for antigen recognition. Thus, hepatic NK cells can develop adaptive immunity to structurally diverse antigens, an activity that requires NK cell-expressed CXCR6.

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia

PubMed Central

Sui, Bing-Dong; Hu, Cheng-Hu; Zheng, Chen-Xi; Shuai, Yi; He, Xiao-Ning; Gao, Ping-Ping; Zhao, Pan; Li, Meng; Zhang, Xin-Yi; He, Tao; Xuan, Kun; Jin, Yan

2017-01-01

Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in various human disorders, but impacts of diseased micro-environments are only beginning to be noticed. Donor diabetic hyperglycemia is reported to impair therapeutic efficacy of stem cells. However, whether recipient diabetic condition also affects MSC-mediated therapy is unknown. We and others have previously shown that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX) mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in recipient type 1 diabetes (T1D). Through intensive glycemic control by daily insulin treatments, therapeutic effects of MSCs on osteopenia were maintained. Interestingly, by only transiently restoration of recipient euglycemia using single insulin injection, MSC infusion could also rescue T1D-induced osteopenia. Conversely, under recipient hyperglycemia induced by glucose injection in OVX mice, MSC-mediated therapeutic effects on osteopenia were diminished. Mechanistically, recipient hyperglycemic micro-environments reduce anti-inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC interaction with T cells via the Adenosine monophosphate-activated protein kinase (AMPK) pathway. We further revealed in diabetic micro-environments, double infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the first transplanted MSCs which normalized the recipient glucose homeostasis. Collectively, our findings uncover a previously unrecognized role of recipient glycemic conditions controlling MSC-mediated therapy, and unravel that fulfillment of potent therapeutic effects of MSCs requires tight control of recipient micro-environments. PMID:28435461

Evaluation of Interruption Behavior by Naive Encoders.

ERIC Educational Resources Information Center

Coon, Christine A.; Schwanenflugel, Paula J.

1996-01-01

Determines the characteristics of interactions that influence judgments of interruption behavior in naive observers. Asks subjects to decide whether an example of an interruption was an interruption and then rate it in terms of how "good" or "bad" it was. Finds that naive observers use some of the same features described in…

Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

PubMed Central

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-01-01

Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

PubMed

Do, Jeong-Su; Visperas, Anabelle; O'Brien, Rebecca L; Min, Booki

2012-04-01

A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells. Here, we report that γδ T cells generated within αβ T cell (or CD4 T cell)-deficient environments displayed altered cytokine profiles; particularly, 'innate' IL-17 expression was significantly impaired compared with those in wild-type mice. Impaired IL-17 production in γδ T cells was directly related to CD4 T-cell deficiency, because depletion of CD4 T cells in wild-type mice diminished and adoptive CD4 T-cell transfer into T-cell receptor β-/- mice restored IL-17 expression in γδ T cells. CD4 T cell-mediated IL-17 expression required TGFβ1. Moreover, Th17 but not Th1 or Th2 effector CD4 T cells were highly efficient in enhancing γδ T-cell IL-17 expression. Taken together, our results highlight a novel CD4 T cell-dependent mechanism that shapes the generation of IL-17+ γδ T cells in naive settings.

CD8+IL-17+ T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

PubMed Central

Dodd-o, Jeffrey M.; Coon, Tiffany A.; Miller, Hannah L.; Ganguly, Sudipto; Popescu, Iulia; O'Donnell, Christopher P.; Cardenes, Nayra; Levine, Melanie; Rojas, Mauricio; Weathington, Nathaniel M.; Zhao, Jing; Zhao, Yutong; McDyer, John F.

2015-01-01

Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet−/− recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice. T-bet−/− recipients demonstrated vigorous allograft rejection at 10 days, characterized by neutrophilic inflammation and predominantly CD8+ T cells producing allospecific IL-17 and/or IFN-γ, in contrast to IFN-γ–dominant responses in WT mice. CD4+ T cells produced IL-17 but not IFN-γ responses in T-bet−/− recipients, in contrast to WT controls. Costimulation blockade using anti-CD154 Ab significantly reduced allospecific CD8+IFN-γ+ responses in both T-bet−/− and WT mice but had no attenuating effect on lung rejection pathology in T-bet−/− recipients or on the development of obliterative airway inflammation that occurred only in T-bet−/− recipients. However, neutralization of IL-17A significantly attenuated costimulation blockade–resistant rejection pathology and airway inflammation in T-bet−/− recipients. In addition, CXCL1 (neutrophil chemokine) was increased in T-bet−/− allografts, and IL-17 induced CXCL1 from mouse lung epithelial cells in vitro. Taken together, our data show that T-bet–deficient recipients of complete MHC-mismatched lung allografts develop costimulation blockade–resistant rejection characterized by neutrophilia and obliterative airway inflammation that is predominantly mediated by CD8+IL-17+ T cells. Our data support T-bet–deficient mouse recipients of lung allografts as a viable animal model to study the immunopathogenesis of small airway injury in lung transplantation

Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK.

PubMed

Rockstroh, Jürgen K; DeJesus, Edwin; Lennox, Jeffrey L; Yazdanpanah, Yazdan; Saag, Michael S; Wan, Hong; Rodgers, Anthony J; Walker, Monica L; Miller, Michael; DiNubile, Mark J; Nguyen, Bach-Yen; Teppler, Hedy; Leavitt, Randi; Sklar, Peter

2013-05-01

STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results. Previously untreated patients without baseline resistance to efavirenz, tenofovir, or emtricitabine were eligible for a randomized study of tenofovir/emtricitabine plus either raltegravir or efavirenz. Yearly analyses were planned, with primary and secondary end points stipulated at weeks 48 and 96, respectively. The primary efficacy outcome was the percentage of patients with viral RNA (vRNA) levels <50 copies per milliliter counting noncompleters as failures (NC=F). Changes from baseline CD4 count were computed using an observed-failure approach to missing data. No formal hypotheses were formulated for testing at week 240. Overall, 71 of 281 raltegravir recipients (25%) and 98 of 282 efavirenz recipients (35%) discontinued the study; discontinuations due to adverse events occurred in 14 (5%) and 28 (10%) patients in the respective groups. In the primary NC=F efficacy analysis at week 240, 198 of 279 (71.0%) raltegravir recipients and 171 of 279 (61.3%) efavirenz recipients had vRNA levels <50 copies per milliliter, yielding a treatment difference {Δ [95% confidence interval (CI)] = 9.5 (1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol-stipulated sensitivity analyses and the prespecified subgroup analyses. The mean (95% CI) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ(95% CI) = 62 (22 to 102)]. Overall, significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects (39.1% vs 64.2%, P < 0.001) or drug-related clinical adverse events (52.0% vs 80.1%, P < 0.001). In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at

Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis.

PubMed

Crespo, Joel; Wu, Ke; Li, Wei; Kryczek, Ilona; Maj, Tomasz; Vatan, Linda; Wei, Shuang; Opipari, Anthony W; Zou, Weiping

2018-05-25

Naive T cells are thought to be functionally quiescent. In this study, we studied and compared the phenotype, cytokine profile, and potential function of human naive CD4 + T cells in umbilical cord and peripheral blood. We found that naive CD4 + T cells, but not memory T cells, expressed high levels of chemokine CXCL8. CXCL8 + naive T cells were preferentially enriched CD31 + T cells and did not express T cell activation markers or typical Th effector cytokines, including IFN-γ, IL-4, IL-17, and IL-22. In addition, upon activation, naive T cells retained high levels of CXCL8 expression. Furthermore, we showed that naive T cell-derived CXCL8 mediated neutrophil migration in the in vitro migration assay, supported tumor sphere formation, and promoted tumor growth in an in vivo human xenograft model. Thus, human naive T cells are phenotypically and functionally heterogeneous and can carry out active functions in immune responses. Copyright © 2018 by The American Association of Immunologists, Inc.

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

PubMed

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-04-30

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

The fate of mesenchymal stem cells transplanted into immunocompetent neonatal mice: implications for skeletal gene therapy via stem cells.

PubMed

Niyibizi, Christopher; Wang, Sujing; Mi, Zhibao; Robbins, Paul D

2004-06-01

To explore the feasibility of skeletal gene and cell therapies, we transduced murine bone marrow-derived mesenchymal stem cells (MSCs) with a retrovirus carrying the enhanced green fluorescent protein and zeocin-resistance genes prior to transplantation into 2-day-old immunocompetent neonatal mice. Whole-body imaging of the recipient mice at 7 days post-systemic cell injection demonstrated a wide distribution of the cells in vivo. Twenty-five days posttransplantation, most of the infused cells were present in the lung as assessed by examination of the cells cultured from the lungs of the recipient mice. The cells persisted in lung and maintained a high level of gene expression and could be recovered from the recipient mice at 150 days after cell transplantation. A significant number of GFP-positive cells were also present in the bones of the recipient mice at 35 days post-cell transplantation. Recycling of the cells recovered from femurs of the recipient mice at 25 days posttransplantation by repeated injections into different neonatal mice resulted in the isolation of a clone of cells that was detected in bone and cartilage, but not in lung and liver after systemic injection. These data demonstrate that MSCs persist in immunocompetent neonatal mice, maintain a high level of gene expression, and may participate in skeletal growth and development of the recipient animals.

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

PubMed

Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

2012-01-01

A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

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

Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.

1991-03-01

Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less

Derivation of novel human ground state naive pluripotent stem cells.

PubMed

Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

2013-12-12

Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

The Preference for Symmetry in Flower-Naive and Not-so-Naive Bumblebees

ERIC Educational Resources Information Center

Plowright, C. M. S.; Evans, S. A.; Leung, J. Chew; Collin, C. A.

2011-01-01

Truly flower-naive bumblebees, with no prior rewarded experience for visits on any visual patterns outside the colony, were tested for their choice of bilaterally symmetric over asymmetric patterns in a radial-arm maze. No preference for symmetry was found. Prior training with rewarded black and white disks did, however, lead to a significant…

Naive Probability: A Mental Model Theory of Extensional Reasoning.

ERIC Educational Resources Information Center

Johnson-Laird, P. N.; Legrenzi, Paolo; Girotto, Vittorio; Legrenzi, Maria Sonino; Caverni, Jean-Paul

1999-01-01

Outlines a theory of naive probability in which individuals who are unfamiliar with the probability calculus can infer the probabilities of events in an "extensional" way. The theory accommodates reasoning based on numerical premises, and explains how naive reasoners can infer posterior probabilities without relying on Bayes's theorem.…

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras

PubMed Central

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R.

2009-01-01

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs. PMID:19182207

Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice.

PubMed

Mutlu, Oguz; Ulak, Güner; Celikyurt, Ipek Komsuoglu; Akar, Füruzan Yildiz; Erden, Faruk; Tanyeri, Pelin

2011-10-01

We investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on visual recognition memory using the novel object recognition (NOR) test in naive and MK-801-treated animals. The effects of drug treatment on locomotion and anxiety were also determined using the open field test. Male Balb-c mice were treated with olanzapine (0.2, 0.4 and 0.6 mg/kg; i.p.), sertindole (0.63, 1.3 and 2.5mg/kg; s.c.) or clozapine (0.5 and 1mg/kg; i.p.), and cognitive deficits were induced by MK-801 (0.2mg/kg; i.p.) administration. Olanzapine treatment decreased the ratio index in the NOR test, whereas sertindole and clozapine had no effect in naive mice. MK-801-induced cognitive impairment was reversed by treatment with olanzapine, sertindole or clozapine. While olanzapine, sertindole and clozapine had no effect on the anxiety of naive mice as determined by the open field test, MK-801 significantly increased the total distance traveled, time spent in the center zone and the velocity of the animals. MK-801-induced effects on locomotion and anxiety in the open field test were reversed by olanzapine, sertindole or clozapine treatment. The results of the present study demonstrated that olanzapine, sertindole and clozapine improved cognition in MK-801 treated mice, and indicate that these drugs have a potential to improve cognition in schizophrenia. Copyright © 2011 Elsevier Inc. All rights reserved.

T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice.

PubMed Central

Powderly, W G; Pier, G B; Markham, R B

1986-01-01

BALB/c mice immunized with Pseudomonas aeruginosa immunotype 1 polysaccharide develop protective T cell immunity to bacterial challenge. In vitro, T cells from immunized mice kill P. aeruginosa by production of a bactericidal lymphokine. The present study demonstrates that adoptive transfer of T cells from immunized BALB/c mice to granulocytopenic mice resulted in 97% survival on challenge with P. aeruginosa, compared with 17% survival with adoptive transfer of T cells from nonimmune BALB/c mice. This protection is specifically elicited by reexposure to the original immunizing antigen; adoptive recipients cannot withstand challenge with immunotype 3 P. aeruginosa. However, the adoptive recipients do survive simultaneous infection with both P. aeruginosa immunotypes 1 and 3. Adoptive transfer of T cells from the congenic CB.20 mice, which are unable to kill P. aeruginosa in vitro, provides only 20% protection to granulocytopenic mice. These studies indicate that transfer of specific immune T lymphocytes can significantly enhance the resistance to P. aeruginosa infection in granulocytopenic mice. PMID:2426306

Induction of cross-priming of naive CD8+ T lymphocytes by recombinant bacillus Calmette-Guerin that secretes heat shock protein 70-major membrane protein-II fusion protein.

PubMed

Mukai, Tetsu; Maeda, Yumi; Tamura, Toshiki; Matsuoka, Masanori; Tsukamoto, Yumiko; Makino, Masahiko

2009-11-15

Because Mycobacterium bovis bacillus Calmette-Guérin (BCG) unconvincingly activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to potentiate the ability of activating naive CD8(+) T cells through dendritic cells (DC). BCG-70M secreted HSP70-MMP-II fusion protein in vitro, which stimulated DC to produce IL-12p70 through TLR2. BCG-70M-infected DC activated not only memory and naive CD8(+) T cells, but also CD4(+) T cells of both types to produce IFN-gamma. The activation of these naive T cells by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC, and was significantly inhibited by pretreatment of DC with chloroquine. Both brefeldin A and lactacystin significantly inhibited the activation of naive CD8(+) T cells by BCG-70M through DC. Thus, the CD8(+) T cell activation may be induced by cross-presentation of Ags through a TAP- and proteosome-dependent cytosolic pathway. When naive CD8(+) T cells were stimulated by BCG-70M-infected DC in the presence of naive CD4(+) T cells, CD62L(low)CD8(+) T cells and perforin-producing CD8(+) T cells were efficiently produced. MMP-II-reactive CD4(+) and CD8(+) memory T cells were efficiently produced in C57BL/6 mice by infection with BCG-70M. These results indicate that BCG-70M activated DC, CD4(+) T cells, and CD8(+) T cells, and the combination of HSP70 and MMP-II may be useful for inducing better T cell activation.

Do the Naive Know Best? The Predictive Power of Naive Ratings of Couple Interactions

ERIC Educational Resources Information Center

Baucom, Katherine J. W.; Baucom, Brian R.; Christensen, Andrew

2012-01-01

We examined the utility of naive ratings of communication patterns and relationship quality in a large sample of distressed couples. Untrained raters assessed 10-min videotaped interactions from 134 distressed couples who participated in both problem-solving and social support discussions at each of 3 time points (pre-therapy, post-therapy, and…

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment.

PubMed

Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R; Kurosky, Alexander; Boldogh, Istvan; Sur, Sanjiv

2016-01-01

Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation.

Naive Juveniles Are More Likely to Become Breeders after Witnessing Predator Mobbing.

PubMed

Griesser, Michael; Suzuki, Toshitaka N

2017-01-01

Responding appropriately during the first predatory attack in life is often critical for survival. In many social species, naive juveniles acquire this skill from conspecifics, but its fitness consequences remain virtually unknown. Here we experimentally demonstrate how naive juvenile Siberian jays (Perisoreus infaustus) derive a long-term fitness benefit from witnessing knowledgeable adults mobbing their principal predator, the goshawk (Accipiter gentilis). Siberian jays live in family groups of two to six individuals that also can include unrelated nonbreeders. Field observations showed that Siberian jays encounter predators only rarely, and, indeed, naive juveniles do not respond to predator models when on their own but do when observing other individuals mobbing them. Predator exposure experiments demonstrated that naive juveniles had a substantially higher first-winter survival after observing knowledgeable group members mobbing a goshawk model, increasing their likelihood of acquiring a breeding position later in life. Previous research showed that naive individuals may learn from others how to respond to predators, care for offspring, or choose mates, generally assuming that social learning has long-term fitness consequences without empirical evidence. Our results demonstrate a long-term fitness benefit of vertical social learning for naive individuals in the wild, emphasizing its evolutionary importance in animals, including humans.

Harnessing the Foreign Body Reaction in Marginal Mass Device-less Subcutaneous Islet Transplantation in Mice.

PubMed

Pepper, Andrew R; Pawlick, Rena; Bruni, Antonio; Gala-Lopez, Boris; Wink, John; Rafiei, Yasmin; Bral, Mariusz; Abualhassan, Nasser; Shapiro, A M James

2016-07-01

Islet transplantation is a successful β-cell replacement therapy for selected patients with type 1 diabetes mellitus. However, despite early insulin independence, long-term graft attrition gradually reverts recipients to exogenous insulin dependency. Undoubtedly, as insulin producing stem cell therapies progress, a transplant site that is retrievable is desirable. This prerequisite is currently incompatible with intrahepatic islet transplantation. Herein, we evaluate the functional capacity of a prevascularized subcutaneous site to accommodate marginal islet mass transplantation in mice. Syngeneic mouse islets (150) were transplanted either under the kidney capsule (KC), into a prevascularized subcutaneous device-less (DL) site, or into the unmodified subcutaneous (SC) tissue. The DL site was created 4 weeks before diabetes induction and islet transplantation through the transient placement of a 5-Fr vascular catheter. Recipient mice were monitored for glycemic control and intraperitoneal glucose tolerance. A marginal islet mass transplanted into the DL site routinely reversed diabetes (n = 13 of 18) whereas all SC islet recipients failed to restore glycemic control (n = 0 of 10, P < 0.01, log-rank). As anticipated, nearly all islet-KC mice (n = 15 of 16) became euglycemic posttransplant. The DL recipients' glucose profiles were comparable to KC islet grafts, postintrapertioneal glucose tolerance testing, whereas SC recipients remained hyperglycemic postglucose challenge. All normoglycemic mice maintained graft function for 100 days until graft retrieval. DL and KC islet grafts stained positively for insulin, microvessels, and a collagen scaffold. The device-less prevascularized approach supports marginal mass islet engraftment in mice.

Understanding of the naive Bayes classifier in spam filtering

NASA Astrophysics Data System (ADS)

Wei, Qijia

2018-05-01

Along with the development of the Internet, the information stream is experiencing an unprecedented burst. The methods of information transmission become more and more important and people receiving effective information is a hot topic in the both research and industry field. As one of the most common methods of information communication, email has its own advantages. However, spams always flood the inbox and automatic filtering is needed. This paper is going to discuss this issue from the perspective of Naive Bayes Classifier, which is one of the applications of Bayes Theorem. Concepts and process of Naive Bayes Classifier will be introduced, followed by two examples. Discussion with Machine Learning is made in the last section. Naive Bayes Classifier has been proved to be surprisingly effective, with the limitation of the interdependence among attributes which are usually email words or phrases.

Naive Theories of Social Groups

ERIC Educational Resources Information Center

Rhodes, Marjorie

2012-01-01

Four studies examined children's (ages 3-10, Total N = 235) naive theories of social groups, in particular, their expectations about how group memberships constrain social interactions. After introduction to novel groups of people, preschoolers (ages 3-5) reliably expected agents from one group to harm members of the other group (rather than…

Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.

PubMed

Lennox, Jeffrey L; Dejesus, Edwin; Berger, Daniel S; Lazzarin, Adriano; Pollard, Richard B; Ramalho Madruga, Jose Valdez; Zhao, Jing; Wan, Hong; Gilbert, Christopher L; Teppler, Hedy; Rodgers, Anthony J; Barnard, Richard J O; Miller, Michael D; Dinubile, Mark J; Nguyen, Bach-Yen; Leavitt, Randi; Sklar, Peter

2010-09-01

We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 2% (-4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.

Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

USDA-ARS?s Scientific Manuscript database

The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

Naive Theory of Biology: The Pre-School Child's Explanation of Death

ERIC Educational Resources Information Center

Vlok, Milandre; de Witt, Marike W.

2012-01-01

This article explains the naive theory of biology that the pre-school child uses to explain the cause of death. The empirical investigation showed that the young participants do use a naive theory of biology to explain function and do make reference to "vitalistic causality" in explaining organ function. Furthermore, most of these…

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment

PubMed Central

Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R.; Kurosky, Alexander; Boldogh, Istvan

2016-01-01

Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation. PMID:26086549

Immunogenicity and safety of the 13-valent Pneumococcal Conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naive and pre-immunized patients under treatment with chronic haemodialysis: a longitudinal quasi-experimental phase IV study.

PubMed

Vandecasteele, S J; De Bacquer, D; Caluwe, R; Ombelet, S; Van Vlem, B

2018-01-01

To benchmark the immunogenicity of pneumococcal conjugated vaccine (PCV-13) versus pneumococcal polysaccharide vaccine (PPV-23) in haemodialysis patients pre-vaccinated or not with PPV-23. The study is a longitudinal quasi-experimental phase IV study in chronic haemodialysis patients aged ≥50 years. Total (ELISA) and functional (opsonophagocytic assay) antibodies after pneumococcal vaccination were quantified at baseline, and after 28 and 365 days. Of 201 eligible patients, 155 were included. Patients were divided in four groups. PPV-23 naive patients were randomized to PPV-23 (40) or PCV-13 (40) vaccination. PPV-23-pre-vaccinated patients were categorized as being vaccinated more (40) or less (35) than 4 years before the study and all received PCV-13. Patients among the four groups had a significant ELISA antibody response for most serotypes that remained significant up to day 365 versus baseline. In PPV-23-naive patients, ELISA antibody titres were significantly higher among PCV-13 versus PPV-23 recipients for six serotypes (1.85-2.34-fold) after 28 days, and remained significantly higher for one serotype (6A, 1.57-fold) after 365 days. Following PCV-13 vaccination, increase in ELISA antibody titres was significantly higher among PPV-23-naive versus PPV-23-pre-vaccinated patients for 12 serotypes after 28 days (1.68-7.74-fold) and remained significantly higher in ten serotypes (1.44-3.29-fold) after 365 days. Immune response after PPV-23 and PCV-13 remains significant for at least 1 year in non-PPV-23-pre-vaccinated patients. Among vaccine-naive haemodialysis patients PCV-13 seems more immunogenic than PPV-23. Immune response to PCV-13 is weaker in PPV-23-pre-vaccinated compared with vaccine-naive patients. Copyright © 2017. Published by Elsevier Ltd.

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

PubMed

Myers, Darienne R; Lau, Tannia; Markegard, Evan; Lim, Hyung W; Kasler, Herbert; Zhu, Minghua; Barczak, Andrea; Huizar, John P; Zikherman, Julie; Erle, David J; Zhang, Weiguo; Verdin, Eric; Roose, Jeroen P

2017-05-23

CD4 + T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4 + T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (T H 2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4 + T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4 + T cell proliferation and uncover a suppressive role for Irf4 in T H 2 polarization; halving Irf4 gene-dosage leads to increases in GATA3 + and IL-4 + cells. Our studies reveal that naive CD4 + T cells are dynamically tuned by tonic LAT-HDAC7 signals. Published by Elsevier Inc.

Calcium-mediated shaping of naive CD4 T-cell phenotype and function

PubMed Central

Guichard, Vincent; Bonilla, Nelly; Durand, Aurélie; Audemard-Verger, Alexandra; Guilbert, Thomas; Martin, Bruno

2017-01-01

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on calcineurin activation. Accordingly, in vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype of their less self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state. PMID:29239722

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

PubMed

Tislerova, Barbora; Brunovsky, Martin; Horacek, Jiri; Novak, Tomas; Kopecek, Miloslav; Mohr, Pavel; Krajca, Vladimír

2008-01-01

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in

Effectiveness of Sofosbuvir and Ribavirin for Eradicating Hepatitis C Virus in Renal Transplant Recipients in Pakistan: Where Resources Are Scarce.

PubMed

Hanif, Farina Muhammad; Laeeq, S Mudassir; Mandhwani, Rajesh Kumar; Luck, Nasir Hassan; Aziz, Tahir; Mehdi, Syed Haider

2017-02-01

Although direct-acting antiviral agents have revolutionized hepatitis C virus treatment, these novel agents are not widely available in the developing world. Further, no treatment recommendation for renal transplant recipients includes these agents. We aimed to evaluate the effectiveness of sofosbuvir and ribavirin, the only direct-acting antiviral agents available in Pakistan, in renal transplant recipients. All renal transplant recipients receiving sofosbuvir and ribavirin from August 2015 to March 2016 were enrolled in the study. Patients' demographics and baseline laboratory parameters were collected. Rapid virologic response, early virologic response, end-of-treatment response, and sustained virologic response at 12 and 24 weeks were analyzed. Statistical analyses were performed using IBM SPSS Statistics software, version 20.0. Of the 37 renal transplant recipients, the mean age was 37.2 ± 10.7 years and the majority (33 [89.2% ]) were men. Twenty-five patients were treatment naive; of the remaining 12 patients, 10 were responders, 2 were nonresponders, and 5 were relapsers to pretransplant hepatitis C treatment. The genotype most commonly seen posttransplant was genotype 1 (56.8%). Rapid virologic response was achieved in 33 patients (89.2%). Early virologic response, end-oftreatment response, and sustained virologic response at 12 weeks were achieved in all 37 patients (100%). Until the time of data collection, 14 patients had achieved a sustained virologic response at 24 weeks. No complications were noted during therapy. In 2 of 4 patients who developed decompensated cirrhosis, treatment led to the resolution of ascites. Sofosbuvir and ribavirin are well tolerated and effective in renal transplant recipients for eradicating hepatitis C virus. Their effectiveness is not limited to renal transplant recipients with genotypes 1, 2, 3, and 4 but also extends to those with mixed genotype (in this study, genotypes 1 and 3).

Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice.

PubMed

Yan, Lin; Yee, John A; Cao, Jay

2013-08-01

The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies.

CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function

PubMed Central

Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Medigeshi, Guruprasad R.

2017-01-01

Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β–T cells (TCRβ–null) are highly susceptible and die over 10–18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage. PMID:28151989

CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

PubMed

Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

2017-02-01

Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

Pathogenesis of Vesicular Stomatitis New Jersey Virus Infection in Deer Mice ( Peromyscus maniculatus) Transmitted by Black Flies ( Simulium vittatum).

PubMed

Mesquita, L P; Diaz, M H; Howerth, E W; Stallknecht, D E; Noblet, R; Gray, E W; Mead, D G

2017-01-01

The natural transmission of vesicular stomatitis New Jersey virus (VSNJV), an arthropod-borne virus, is not completely understood. Rodents may have a role as reservoir or amplifying hosts. In this study, juvenile and nestling deer mice ( Peromyscus maniculatus) were exposed to VSNJV-infected black fly ( Simulium vittatum) bites followed by a second exposure to naive black flies on the nestling mice. Severe neurological signs were observed in some juvenile mice by 6 to 8 days postinoculation (DPI); viremia was not detected in 25 juvenile deer mice following exposure to VSNJV-infected fly bites. Both juvenile and nestling mice had lesions and viral antigen in the central nervous system (CNS); in juveniles, their distribution suggested that the sensory pathway was the most likely route to the CNS. In contrast, a hematogenous route was probably involved in nestling mice, since all of these mice developed viremia and had widespread antigen distribution in the CNS and other tissues on 2 DPI. VSNJV was recovered from naive flies that fed on viremic nestling mice. This is the first report of viremia in a potential natural host following infection with VSNJV via insect bite and conversely of an insect becoming infected with VSNJV by feeding on a viremic host. These results, along with histopathology and immunohistochemistry, show that nestling mice have widespread dissemination of VSNJV following VSNJV-infected black fly bite and are a potential reservoir or amplifying host for VSNJV.

The Persistence of "Solid" and "Liquid" Naive Conceptions: A Reaction Time Study

ERIC Educational Resources Information Center

Babai, Reuven; Amsterdamer, Anat

2008-01-01

The study explores whether the naive concepts of "solid" and "liquid" persist in adolescence. Accuracy of responses and reaction times where measured while 41 ninth graders classified different solids (rigid, non-rigid and powders) and different liquids (runny, dense) into solid or liquid. The results show that these naive conceptions affect…

Remarkable Changes in Behavior and Physiology of Laboratory Mice after the Massive 2011 Tohoku Earthquake in Japan

PubMed Central

Yanai, Shuichi; Semba, Yuki; Endo, Shogo

2012-01-01

A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake’s epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. “Earthquake-experienced” mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology. PMID:22957073

HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

PubMed

Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

2017-10-24

B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

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

Guo, Yixian; Zhang, Lanfang; Wan, Suigui

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the currentmore » study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.« less

What Fits into a Mirror: Naive Beliefs about the Field of View

ERIC Educational Resources Information Center

Bianchi, Ivana; Savardi, Ugo

2012-01-01

Research on naive physics and naive optics have shown that people hold surprising beliefs about everyday phenomena that are in contrast with what they see. In this article, we investigated what adults expect to be the field of view of a mirror from various viewpoints. The studies presented here confirm that humans have difficulty dealing with the…

Impaired processing speed and attention in first-episode drug naive schizophrenia with deficit syndrome.

PubMed

Chen, Ce; Jiang, Wenhui; Zhong, Na; Wu, Jin; Jiang, Haifeng; Du, Jiang; Li, Ye; Ma, Xiancang; Zhao, Min; Hashimoto, Kenji; Gao, Chengge

2014-11-01

Although first-episode drug naive patients with schizophrenia are known to show cognitive impairment, the cognitive performances of these patients, who suffer deficit syndrome, compared with those who suffer non-deficit syndrome is undetermined. The aim of this study was to compare cognitive performances in first-episode drug-naive schizophrenia with deficit syndrome or non-deficit syndrome. First-episode drug naive patients (n=49) and medicated patients (n=108) with schizophrenia, and age, sex, and education matched healthy controls (n=57 for the first-episode group, and n=128 for the medicated group) were enrolled. Patients were divided into deficit or non-deficit syndrome groups, using the Schedule for Deficit Syndrome. Cognitive performance was assessed using the CogState computerized cognitive battery. All cognitive domains in first-episode drug naive and medicated patients showed significant impairment compared with their respective control groups. Furthermore, cognitive performance in first-episode drug naive patients was significantly worse than in medicated patients. Interestingly, the cognitive performance markers of processing speed and attention, in first-episode drug naive patients with deficit syndrome, were both significantly worse than in equivalent patients without deficit syndrome. In contrast, no differences in cognitive performance were found between the two groups of medicated patients. In conclusion, this study found that first-episode drug naive schizophrenia with deficit syndrome showed significantly impaired processing speed and attention, compared with patients with non-deficit syndrome. These findings highlight processing speed and attention as potential targets for pharmacological and psychosocial interventions in first-episode schizophrenia with deficit syndrome, since these domains are associated with social outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

Top predators affect the composition of naive protist communities, but only in their early-successional stage.

PubMed

Zander, Axel; Gravel, Dominique; Bersier, Louis-Félix; Gray, Sarah M

2016-02-01

Introduced top predators have the potential to disrupt community dynamics when prey species are naive to predation. The impact of introduced predators may also vary depending on the stage of community development. Early-succession communities are likely to have small-bodied and fast-growing species, but are not necessarily good at defending against predators. In contrast, late-succession communities are typically composed of larger-bodied species that are more predator resistant relative to small-bodied species. Yet, these aspects are greatly neglected in invasion studies. We therefore tested the effect of top predator presence on early- and late-succession communities that were either naive or non-naive to top predators. We used the aquatic community held within the leaves of Sarracenia purpurea. In North America, communities have experienced the S. purpurea top predator and are therefore non-naive. In Europe, this predator is not present and its niche has not been filled, making these communities top-predator naive. We collected early- and late-succession communities from two non-naive and two naive sites, which are climatically similar. We then conducted a common-garden experiment, with and without the presence of the top predator, in which we recorded changes in community composition, body size spectra, bacterial density, and respiration. We found that the top predator had no statistical effect on global measures of community structure and functioning. However, it significantly altered protist composition, but only in naive, early-succession communities, highlighting that the state of community development is important for understanding the impact of invasion.

Children and Adolescents' Understandings of Family Resemblance: A Study of Naive Inheritance Concepts

ERIC Educational Resources Information Center

Williams, Joanne M.

2012-01-01

This paper aims to provide developmental data on two connected naive inheritance concepts and to explore the coherence of children's naive biology knowledge. Two tasks examined children and adolescents' (4, 7, 10, and 14 years) conceptions of phenotypic resemblance across kin (in physical characteristics, disabilities, and personality traits). The…

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

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

Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation ofmore » recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.« less

Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection.

PubMed

Inomata, Takenori; Hua, Jing; Nakao, Takeshi; Shiang, Tina; Chiang, Homer; Amouzegar, Afsaneh; Dana, Reza

2018-01-01

To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection. Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCII CD11c DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ and IL-17 CD4 T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group). Recipients of DED donor corneas showed significantly reduced graft survival (10%) compared with control mice (50% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0% ± 0.36% vs. healthy donor 35.4 ± 0.5%; P < 0.0001) and host dLNs (DED donor 25.1% ± 0.66% vs. healthy donor 13.7% ± 1.6%; P = 0.005). Frequencies of IFN-γ and IL-17 T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 ± 193 vs. healthy donor 6806 ± 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED (P = 0.0146). Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.

IL-7-Induced Proliferation of Human Naive CD4 T-Cells Relies on Continued Thymic Activity.

PubMed

Silva, Susana L; Albuquerque, Adriana S; Matoso, Paula; Charmeteau-de-Muylder, Bénédicte; Cheynier, Rémi; Ligeiro, Dário; Abecasis, Miguel; Anjos, Rui; Barata, João T; Victorino, Rui M M; Sousa, Ana E

2017-01-01

Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms of the naive compartment to counteract the loss of de novo CD4 T-cell generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence of thymopoiesis and compared with age-matched controls. We found that the preservation of the CD31 - subset was independent of the thymus and that its size is tightly controlled by peripheral mechanisms, including prolonged cell survival as attested by Bcl-2 levels. Conversely, a significant contraction of the CD31 + naive subset was observed in the absence of thymic activity. This was associated with impaired responses of purified naive CD4 T-cells to IL-7, namely, in vitro proliferation and upregulation of CD31 expression, which likely potentiated the decline in recent thymic emigrants. Additionally, we found no apparent constraint in the differentiation of naive cells into the memory compartment in individuals completely lacking thymic activity despite upregulation of DUSP6 , a phosphatase associated with increased TCR threshold. Of note, thymectomized individuals featuring some degree of thymopoiesis were able to preserve the size and diversity of the naive CD4 compartment, further arguing against complete thymectomy in infancy. Overall, our data suggest that robust peripheral mechanisms ensure the homeostasis of CD31 - naive CD4 pool and point to the requirement of continuous thymic activity to the maintenance of IL-7-driven homeostatic proliferation of CD31 + naive CD4 T-cells, which is essential to secure T-cell diversity throughout life.

Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.

PubMed

Yap, Jin Yan; Wirasinha, Rushika C; Chan, Anna; Howard, Debbie R; Goodnow, Christopher C; Daley, Stephen R

2018-02-07

Acquisition of T-cell central tolerance involves distinct pathways of self-antigen presentation to thymocytes. One pathway termed indirect presentation requires a self-antigen transfer step from thymic epithelial cells (TECs) to bone marrow-derived cells before the self-antigen is presented to thymocytes. The role of indirect presentation in central tolerance is context-dependent, potentially due to variation in self-antigen expression, processing and presentation in the thymus. Here, we report experiments in mice in which TECs expressed a membrane-bound transgenic self-antigen, hen egg lysozyme (HEL), from either the insulin (insHEL) or thyroglobulin (thyroHEL) promoter. Intrathymic HEL expression was less abundant and more confined to the medulla in insHEL mice compared with thyroHEL mice. When indirect presentation was impaired by generating mice lacking MHC class II expression in bone marrow-derived antigen-presenting cells, insHEL-mediated thymocyte deletion was abolished, whereas thyroHEL-mediated deletion occurred at a later stage of thymocyte development and Foxp3 + regulatory T-cell differentiation increased. Indirect presentation increased the strength of T-cell receptor signalling that both self-antigens induced in thymocytes, as assessed by Helios expression. Hence, indirect presentation limits the differentiation of naive and regulatory T cells by promoting deletion of self-reactive thymocytes. © 2018 John Wiley & Sons Ltd.

Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells.

PubMed

Lin, Gu-Jiun; Sytwu, Huey-Kang; Yu, Jyh-Cherng; Chen, Yuan-Wu; Kuo, Yu-Liang; Yu, Chiao-Chi; Chang, Hao-Ming; Chan, De-Chuan; Huang, Shing-Hwa

2015-01-15

Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. Copyright © 2014. Published by Elsevier Inc.

Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

PubMed

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-04-01

Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

NASA Astrophysics Data System (ADS)

Liu, Lanxia; Bai, Yuanyuan; Zhu, Dunwan; Song, Liping; Wang, Hai; Dong, Xia; Zhang, Hailing; Leng, Xigang

2011-06-01

Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells. The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells. It was also demonstrated that, when directly exposed to the naive CD4+ T cells, the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4+ T cell polarization, nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines.

Improving Naive Bayes with Online Feature Selection for Quick Adaptation to Evolving Feature Usefulness

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

Pon, R K; Cardenas, A F; Buttler, D J

The definition of what makes an article interesting varies from user to user and continually evolves even for a single user. As a result, for news recommendation systems, useless document features can not be determined a priori and all features are usually considered for interestingness classification. Consequently, the presence of currently useless features degrades classification performance [1], particularly over the initial set of news articles being classified. The initial set of document is critical for a user when considering which particular news recommendation system to adopt. To address these problems, we introduce an improved version of the naive Bayes classifiermore » with online feature selection. We use correlation to determine the utility of each feature and take advantage of the conditional independence assumption used by naive Bayes for online feature selection and classification. The augmented naive Bayes classifier performs 28% better than the traditional naive Bayes classifier in recommending news articles from the Yahoo! RSS feeds.« less

Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation.

PubMed

Scroggins, Sabrina M; Olivier, Alicia K; Meyerholz, David K; Schlueter, Annette J

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC may

Characterization of Regulatory Dendritic Cells That Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation

PubMed Central

Scroggins, Sabrina M.; Olivier, Alicia K.; Meyerholz, David K.; Schlueter, Annette J.

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3–4 months) and older (14–18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC

20 CFR 641.881 - What are the SCSEP recipient's responsibilities relating to awards to sub-recipients?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What are the SCSEP recipient's responsibilities relating to awards to sub-recipients? 641.881 Section 641.881 Employees' Benefits EMPLOYMENT AND... awards to sub-recipients? (a) Recipients are responsible for ensuring that all awards to sub-recipients...

20 CFR 641.881 - What are the SCSEP recipient's responsibilities relating to awards to sub-recipients?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false What are the SCSEP recipient's responsibilities relating to awards to sub-recipients? 641.881 Section 641.881 Employees' Benefits EMPLOYMENT AND... awards to sub-recipients? (a) Recipients are responsible for ensuring that all awards to sub-recipients...

20 CFR 641.881 - What are the SCSEP recipient's responsibilities relating to awards to sub-recipients?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false What are the SCSEP recipient's responsibilities relating to awards to sub-recipients? 641.881 Section 641.881 Employees' Benefits EMPLOYMENT AND... awards to sub-recipients? (a) Recipients are responsible for ensuring that all awards to sub-recipients...

The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.

PubMed

AlDabbagh, M A; Gitman, M R; Kumar, D; Humar, A; Rotstein, C; Husain, S

2017-03-01

The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.

PubMed

Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas; Baums, Christoph G

2014-06-01

Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3(-/-) mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3(-/-) mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR(-/-) mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.

Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial.

PubMed

Walmsley, Sharon; Baumgarten, Axel; Berenguer, Juan; Felizarta, Franco; Florence, Eric; Khuong-Josses, Marie-Aude; Kilby, J Michael; Lutz, Thomas; Podzamczer, Daniel; Portilla, Joaquin; Roth, Norman; Wong, Deborah; Granier, Catherine; Wynne, Brian; Pappa, Keith

2015-12-15

The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of <50 copies per milliliter through W144 (P = 0.01). Superior efficacy was primarily driven by fewer discontinuations due to adverse events in the dolutegravir + abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144.

2 CFR 200.86 - Recipient.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AWARDS Acronyms and Definitions Acronyms § 200.86 Recipient. Recipient means a non-Federal entity that... program. The term recipient does not include subrecipients. See also § 200.69 Non-Federal entity. ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Recipient. 200.86 Section 200.86 Grants and...

The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells.

PubMed

Ndifon, Wilfred; Dushoff, Jonathan

2016-06-15

Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells. In this paper, we propose an even simpler explanation: that it results from the loss of T cells that have attained replicative senescence (i.e., the Hayflick limit). Stochastic numerical simulations of naive T cell population dynamics, based on experimental parameters, show that the rate of homeostatic T cell proliferation increases after the age of ∼60 y because naive T cells collectively approach replicative senescence. This leads to a sharp decline of effective clonal diversity after ∼70 y, in agreement with empirical data. A mathematical analysis predicts that, without an increase in the naive T cell proliferation rate, this decline will occur >50 yr later than empirically observed. These results are consistent with a model in which exhaustion of the proliferative capacity of naive T cells causes a sharp decline of their effective clonal diversity and imply that therapeutic potentiation of thymopoiesis might either prevent or reverse this outcome. Copyright © 2016 by The American Association of Immunologists, Inc.

Survival of iPSC-derived grafts within the striatum of immunodeficient mice: Importance of developmental stage of both transplant and host recipient.

PubMed

Tom, Colton M; Younesi, Shahab; Meer, Elana; Bresee, Catherine; Godoy, Marlesa; Mattis, Virginia B

2017-11-01

Degeneration of the striatum can occur in multiple disorders with devastating consequences for the patients. Infantile infections with streptococcus, measles, or herpes can cause striatal necrosis associated with dystonia or dyskinesia; and in patients with Huntington's disease the striatum undergoes massive degeneration, leading to behavioral, psychological and movement issues, ultimately resulting in death. Currently, only supportive therapies are available for striatal degeneration. Clinical trials have shown some efficacy using transplantation of fetal-derived primary striatal progenitors. Large banks of fetal progenitors that give rise to medium spiny neurons (MSNs), the primary neuron of the striatum, are needed to make transplantation therapy a reality. However, fetal tissue is of limited supply, has ethical concerns, and is at risk of graft immunorejection. An alternative potential source of MSNs is induced pluripotent stem cells (iPSCs), adult somatic tissues reprogrammed back to a stem cell fate. Multiple publications have demonstrated the ability to differentiate striatal MSNs from iPSCs. Previous publications have demonstrated that the efficacy of fetal progenitor transplants is critically dependent upon the age of the donor embryo/fetus as well as the age of the transplant recipient. With the advent of iPSC technology, a question that remains unanswered concerns the graft's "age," which is crucial since transplanting pluripotent cells has an inherent risk of over proliferation and teratoma formation. Therefore, in order to also determine the effect of transplant recipient age on the graft, iPSCs were differentiated to three stages along a striatal differentiation paradigm and transplanted into the striatum of both neonatal and adult immunodeficient mice. This study demonstrated that increased murine transplant-recipient age (adult vs neonate) resulted in decreased graft survival and volume/rostro-caudal spread after six weeks in vivo, regardless of

Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.

PubMed

Kelschenbach, Jennifer L; Saini, Manisha; Hadas, Eran; Gu, Chao-Jiang; Chao, Wei; Bentsman, Galina; Hong, Jessie P; Hanke, Tomas; Sharer, Leroy R; Potash, Mary Jane; Volsky, David J

2012-06-01

Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

Increased postischemic brain injury in mice deficient in uracil-DNA glycosylase

PubMed Central

Endres, Matthias; Biniszkiewicz, Detlev; Sobol, Robert W.; Harms, Christoph; Ahmadi, Michael; Lipski, Andreas; Katchanov, Juri; Mergenthaler, Philipp; Dirnagl, Ulrich; Wilson, Samuel H.; Meisel, Andreas; Jaenisch, Rudolf

2004-01-01

Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues in nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, and phenotypically normal and have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase in the uracil/cytosine ratio in the genome and augmented cell death. After combined oxygen-glucose deprivation, Ung–/– primary cortical neurons have increased vulnerability to cell death, which is associated with early mitochondrial dysfunction. In vivo, UNG expression and activity are low in brains of naive WT mice but increase significantly after reversible middle cerebral artery occlusion and reperfusion. Moreover, major increases in infarct size are observed in Ung–/– mice compared with littermate control mice. In conclusion, our results provide compelling evidence that UNG is of major importance for tissue repair after brain ischemia. PMID:15199406

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

PubMed

Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

2004-08-27

The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse.

PubMed

Reichardt, Peter; Dornbach, Bastian; Rong, Song; Beissert, Stefan; Gueler, Faikah; Loser, Karin; Gunzer, Matthias

2007-09-01

Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses.

Belatacept for kidney transplant recipients.

PubMed

Masson, Philip; Henderson, Lorna; Chapman, Jeremy R; Craig, Jonathan C; Webster, Angela C

2014-11-24

Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a kidney transplant to lose the function of their transplanted kidney necessitating return to dialysis is chronic kidney transplant scarring. Immunosuppressant drugs have side effects that increase risks of cardiovascular disease, cancer and chronic kidney transplant scarring. Belatacept may provide sufficient immunosuppression while avoiding unwanted side effects of other immunosuppressant drugs. However, high rates of post-transplant lymphoproliferative disease (PTLD) have been reported when belatacept is used in particular kidney transplant recipients at high dosage. 1) Compare the relative efficacy of belatacept versus any other primary immunosuppression regimen for preventing acute rejection, maintaining kidney transplant function, and preventing death. 2) Compare the incidence of several adverse events: PTLD; other malignancies; chronic transplant kidney scarring (IF/TA); infections; change in blood pressure, lipid and blood sugar control. 3) Assess any variation in effects by study, intervention and recipient characteristics, including: differences in pre-transplant Epstein Barr virus serostatus; belatacept dosage; and donor-category (living, standard criteria deceased, or extended criteria deceased). We searched the Cochrane Renal Group's Specialised Register to 1 September 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials (RCT) that compared belatacept versus any other immunosuppression regimen in kidney transplant recipients were eligible for inclusion. Two authors independently extracted data for study quality and transplant outcomes and synthesized results using random effects meta-analysis, expressed as risk ratios (RR) and mean differences (MD), both with 95% confidence intervals (CI).  Subgroup analyses and

49 CFR 32.660 - Recipient.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Recipient. 32.660 Section 32.660 Transportation... ASSISTANCE) Definitions § 32.660 Recipient. Recipient means any individual, corporation, partnership... award directly from a Federal agency. ...

49 CFR 32.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Recipient. 32.660 Section 32.660 Transportation... ASSISTANCE) Definitions § 32.660 Recipient. Recipient means any individual, corporation, partnership... award directly from a Federal agency. ...

22 CFR 133.660 - Recipient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Recipient. 133.660 Section 133.660 Foreign... ASSISTANCE) Definitions § 133.660 Recipient. Recipient means any individual, corporation, partnership... award directly from a Federal agency. ...

IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells.

PubMed

Alves, Nuno L; Arosa, Fernando A; van Lier, René A W

2005-07-15

Human naive CD8+ T cells are able to respond in an Ag-independent manner to IL-7 and IL-15. Whereas IL-7 largely maintains CD8+ T cells in a naive phenotype, IL-15 drives these cells to an effector phenotype characterized, among other features, by down-regulation of the costimulatory molecule CD28. We evaluated the influence of the CD4+ Th cell-derived common gamma-chain cytokine IL-21 on cytokine-induced naive CD8+ T cell activation. Stimulation with IL-21 did not induce division and only slightly increased IL-15-induced proliferation of naive CD8+ T cells. Strikingly, however, IL-15-induced down-modulation of CD28 was completely prevented by IL-21 at the protein and transcriptional level. Subsequent stimulation via combined TCR/CD3 and CD28 triggering led to a markedly higher production of IL-2 and IFN-gamma in IL-15/IL-21-stimulated cells compared with IL-15-stimulated T cells. Our data show that IL-21 modulates the phenotype of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands.

Left Ventricular Strain in Chemotherapy-Naive and Radiotherapy-Naive Patients With Cancer.

PubMed

Tadic, Marijana; Genger, Martin; Baudisch, Ana; Kelle, Sebastian; Cuspidi, Cesare; Belyavskiy, Evgeny; Burkhardt, Franziska; Venneri, Lucia; Attanasio, Philipp; Pieske, Burkert

2018-03-01

We sought to investigate left ventricular (LV) function and mechanics in patients with cancer before they received chemotherapy or radiotherapy, as well as the relationship between cancer and reduced LV multidirectional strain in the whole study population. The retrospective study involved 122 chemotherapy- and radiotherapy-naive patients with cancer and 45 age- and sex-matched controls with a cardiovascular risk profile similar to that of the patients with cancer. All the patients underwent echocardiographic examination before introduction of chemotherapy or radiotherapy. LV longitudinal (-19.1% ± 2.1% vs -17.8% ± 3.5%; P = 0.022), circumferential (-22.9% ± 3.5% vs -20.1% ± 4.1%; P < 0.001), and radial (40.5% ± 8.8% vs 35.2% ± 10.7%; P = 0.004) strain was significantly lower in the patients with cancer than in the control group. Endocardial and midmyocardial longitudinal LV strain was significantly reduced in the patients with cancer compared with the controls, whereas epicardial longitudinal strain was similar between these groups. Endocardial, midmyocardial, and epicardial circumferential strain was significantly lower in the chemotherapy- or radiotherapy-naive patients with cancer than in the controls. Cancer was associated with reduced longitudinal (odds ratio [OR], 9.0; 95% confidence interval [CI], 2.20-23.50; P < 0.001), reduced circumferential (OR, 7.1; 95% CI, 3.80-20.40; P < 0.001), and reduced radial strain (OR, 7.2; 95% CI, 3.41-25.10; P < 0.001) independent of age, sex, body mass index, diabetes, and hypertension. LV mechanics was impaired in the patients with cancer compared with the controls even before initiation of chemotherapy and radiotherapy. Cancer and hypertension were associated with reduced LV multidirectional strain independent of other clinical parameters. The present results indicate that cancer itself potentially induces cardiac remodelling independent of chemotherapy and radiotherapy. Copyright © 2017 Canadian

Prevention and reversal of experimental autoimmune thyroiditis (EAT) in mice by administration of anti-L3T4 monoclonal antibody at different stages of disease development.

PubMed

Stull, S J; Kyriakos, M; Sharp, G C; Braley-Mullen, H

1988-11-01

Experimental autoimmune thyroiditis (EAT) can be induced in CBA/J mice following the transfer of spleen cells from mouse thyroglobulin (MTg)-sensitized donors that have been activated in vitro with MTg. Since L3T4+ T cells are required to transfer EAT in this model, the present study was undertaken to assess the effectiveness of the anti-L3T4 monoclonal antibody (mAb) GK1.5 in preventing or arresting the development of EAT. Spleen cells from mice given mAb GK1.5 prior to sensitization with MTg and adjuvant could not transfer EAT to normal recipients and cells from these mice did not proliferate in vitro to MTg. Donor mice given GK1.5 before immunization did not develop anti-MTg autoantibody and recipients of cells from such mice also produced little anti-MTg. GK1.5 could also prevent the proliferation and activation of sensitized effector cell precursors when added to in vitro cultures. When a single injection of mAb GK1.5 was given to recipients of in vitro-activated spleen cells, EAT was reduced whether the mAb was given prior to cell transfer or as late as 19 days after cell transfer. Whereas the incidence and severity of EAT was consistently reduced by injecting recipient mice with GK1.5, the same mice generally had no reduction in anti-MTg autoantibody. Since EAT is consistently induced in control recipients by 14-19 days after cell transfer, the ability of mAb GK1.5 to inhibit EAT when injected 14 or 19 days after cell transfer indicates that a single injection of the mAb GK1.5 can cause reversal of the histopathologic lesions of EAT in mice. These studies further establish the important role of L3T4+ T cells in the pathogenesis of EAT in mice and also suggest that therapy with an appropriate mAb may be an effective treatment for certain autoimmune diseases even when the therapy is initiated late in the course of the disease.

Social Defeat: Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice

PubMed Central

Narayanan, Venu; Heiming, Rebecca S.; Jansen, Friederike; Lesting, Jörg; Sachser, Norbert; Pape, Hans-Christian; Seidenbecher, Thomas

2011-01-01

Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (−/−) and heterozygous (+/−) mice. Naive males and experienced losers (generated in a resident-intruder paradigm) of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/− mice, 5-HTT−/− mice showed impaired recall of extinction. In addition, 5-HTT−/− and +/− experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/− and +/− losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT−/− naive and in 5-HTT−/− and +/− loser mice. In conclusion, extinction learning and memory of conditioned fear

Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells.

PubMed

Uchiyama, Masateru; Jin, Xiangyuan; Zhang, Qi; Hirai, Toshihito; Amano, Atsushi; Bashuda, Hisashi; Niimi, Masanori

2012-03-23

Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of

Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

PubMed Central

2012-01-01

Background Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Methods Naïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. Results CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to

22 CFR 1509.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Recipient. 1509.660 Section 1509.660 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.660 Recipient. Recipient means any individual, corporation, partnership...

20 CFR 439.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Recipient. 439.660 Section 439.660 Employees' Benefits SOCIAL SECURITY ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 439.660 Recipient. Recipient means any individual, corporation, partnership...

22 CFR 1008.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Recipient. 1008.660 Section 1008.660 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1008.660 Recipient. Recipient means any individual, corporation, partnership...

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

PubMed Central

Koch, Janne; Hau, Jann; Pravsgaard Christensen, Jan; Elvang Jensen, Henrik; Bagge Hansen, Morten; Rieneck, Klaus

2013-01-01

Few experimental models are available for the study of natural resistance to cancer. One of them is the SR/CR (spontaneous regression/complete resistance) mouse model in which natural resistance to a variety of cancer types appeared to be inherited in SR/CR strains of BALB/c and C57BL/6 mice. The genetic, cellular, and molecular effector mechanisms in this model are largely unknown, but cells from the innate immune system may play a significant role. In contrast to previous observations, the cancer resistance was limited to S180 sarcoma cancer cells. We were unable to confirm previous observations of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding recipient mice, the cancer disappeared gradually following infiltration of a large number of polymorphonuclear granulocytes and remarkably few lymphocytes in the remaining tumor tissues. This study confirmed that the in vivo growth and spread of cancer cells depend on a complex interplay between the cancer cells and the host organism. Here, hereditary components of the immune system, most likely the innate part, played a crucial role in this interplay and lead to resistance to a single experimental cancer type. The fact that leukocytes depleted of both CD4+/CD8+ and B cells from the cancer resistant donor mice could be transferred to inhibit S180 cancer cell growth in susceptible recipient mice support the vision of an efficient and adverse event free immunotherapy in future selected cancer types. PMID:23555858

Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis

PubMed Central

Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas

2014-01-01

Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3−/− mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3−/− mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3−/− mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3−/− blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR−/− mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity. PMID:24686060

Transplantation of bone marrow-derived mesenchymal stem cells rescues partially rachitic phenotypes induced by 1,25-Dihydroxyvitamin D deficiency in mice

PubMed Central

Zhang, Zengli; Yin, Shaomeng; Xue, Xian; Ji, Ji; Tong, Jian; Goltzman, David; Miao, Dengshun

2016-01-01

To determine whether the transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can improve the 1,25(OH)2D deficiency-induced rachitic phenotype, 2×106 BM-MSCs from wild-type mice or vehicle were transplanted by tail vein injection into mice deficient in 1,25(OH)2D due to targeted deletion of 1α(OH)ase (1α(OH)ase-/-). Our results show that 1α(OH)ase mRNA was expressed in the BM-MSCs derived from wild-type mice, and was detected in long bone, kidney and intestine from BM-MSC-transplanted 1α(OH)ase-/- recipients. Serum calcium, 1,25(OH)2D3 levels and body weight were significantly increased in BM-MSC-transplanted 1α(OH)ase-/- recipients compared to vehicle-treated 1α(OH)ase-/- mice. Skeletal mineralization improved in 1α(OH)ase-/- recipients as demonstrated by BMD measurement, micro-CT analysis and von Kossa staining of undecalcified sections. Expression levels of type I collagen, osteocalcin, bone sialoprotein and vitronectin and the size of calcified nodules were decreased in BM-MSC cultures from 1α(OH)ase-/- mice compared with those from wild-type mice, however, these parameters were increased in those from BM-MSCs-transplanted 1α(OH)ase-/- recipients compared with those from vehicle-treated 1α(OH)ase-/- mice. This study indicates that donor BM-MSCs cells can relocate to multiple tissues where they synthesize 1α(OH)ase and produce 1,25(OH)2D that contributes to the improvement of serum calcium and skeletal mineralization. Results from this study suggest that BM-MSC transplantation may provide a therapeutic approach to treatment of pseudovitamin D-deficiency rickets. PMID:27830022

Transplantation of bone marrow-derived mesenchymal stem cells rescues partially rachitic phenotypes induced by 1,25-Dihydroxyvitamin D deficiency in mice.

PubMed

Zhang, Zengli; Yin, Shaomeng; Xue, Xian; Ji, Ji; Tong, Jian; Goltzman, David; Miao, Dengshun

2016-01-01

To determine whether the transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can improve the 1,25(OH) 2 D deficiency-induced rachitic phenotype, 2×10 6 BM-MSCs from wild-type mice or vehicle were transplanted by tail vein injection into mice deficient in 1,25(OH) 2 D due to targeted deletion of 1α(OH)ase (1α(OH)ase -/- ). Our results show that 1α(OH)ase mRNA was expressed in the BM-MSCs derived from wild-type mice, and was detected in long bone, kidney and intestine from BM-MSC-transplanted 1α(OH)ase -/- recipients. Serum calcium, 1,25(OH) 2 D 3 levels and body weight were significantly increased in BM-MSC-transplanted 1α(OH)ase -/- recipients compared to vehicle-treated 1α(OH)ase -/- mice. Skeletal mineralization improved in 1α(OH)ase -/- recipients as demonstrated by BMD measurement, micro-CT analysis and von Kossa staining of undecalcified sections. Expression levels of type I collagen, osteocalcin, bone sialoprotein and vitronectin and the size of calcified nodules were decreased in BM-MSC cultures from 1α(OH)ase -/- mice compared with those from wild-type mice, however, these parameters were increased in those from BM-MSCs-transplanted 1α(OH)ase -/- recipients compared with those from vehicle-treated 1α(OH)ase -/- mice. This study indicates that donor BM-MSCs cells can relocate to multiple tissues where they synthesize 1α(OH)ase and produce 1,25(OH) 2 D that contributes to the improvement of serum calcium and skeletal mineralization. Results from this study suggest that BM-MSC transplantation may provide a therapeutic approach to treatment of pseudovitamin D-deficiency rickets.

10 CFR 607.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Recipient. 607.660 Section 607.660 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.660 Recipient. Recipient means any individual, corporation, partnership...

13 CFR 147.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Recipient. 147.660 Section 147.660 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Definitions § 147.660 Recipient. Recipient means any individual, corporation...

34 CFR 84.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Recipient. 84.660 Section 84.660 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.660 Recipient. Recipient means any individual, corporation, partnership...

22 CFR 312.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Recipient. 312.660 Section 312.660 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.660 Recipient. Recipient means any individual, corporation, partnership, association, unit of...

Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant protein as carrier.

PubMed

Guirola, María; Urquiza, Dioslaida; Alvarez, Anabel; Cannan-Haden, Leonardo; Caballero, Evelin; Guillén, Gerardo

2006-03-01

In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.

Antiorthostatic suspension stimulates profiles of macrophage activation in mice

NASA Technical Reports Server (NTRS)

Miller, E. S.; Bates, R. A.; Koebel, D. A.; Sonnenfeld, G.

1999-01-01

The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

45 CFR 1155.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recipient. 1155.660 Section 1155.660 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE... ASSISTANCE) Definitions § 1155.660 Recipient. Recipient means any individual, corporation, partnership...

45 CFR 630.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recipient. 630.660 Section 630.660 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.660 Recipient. Recipient means any...

28 CFR 83.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recipient. 83.660 Section 83.660 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.660 Recipient. Recipient means any individual, corporation, partnership, association, unit of...

21 CFR 1405.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Recipient. 1405.660 Section 1405.660 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.660 Recipient. Recipient means any individual, corporation...

CD44 gene vaccination for insulin-dependent diabetes mellitus in non-obese diabetic mice.

PubMed

Weiss, Lola; Botero-Anug, Ana Maria; Hand, Carla; Slavin, Shimon; Naor, David

2008-01-01

Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus. To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM in a transfer model of NOD mice. Our vaccination technique involved the insertion of CD44s or CD44v cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN were implanted 20 days before and 3 days after cell transfer. In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed. These findings may open new opportunities for IDDM therapy in the future.

31 CFR 20.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recipient. 20.660 Section 20.660 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.660 Recipient. Recipient means any individual...

31 CFR 20.660 - Recipient.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Recipient. 20.660 Section 20.660 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.660 Recipient. Recipient means any individual...

31 CFR 20.660 - Recipient.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Recipient. 20.660 Section 20.660 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.660 Recipient. Recipient means any individual...

31 CFR 20.660 - Recipient.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Recipient. 20.660 Section 20.660 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.660 Recipient. Recipient means any individual...

31 CFR 20.660 - Recipient.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Recipient. 20.660 Section 20.660 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.660 Recipient. Recipient means any individual...

From Welfare to Work: The Endorsement of the Money Ethic and the Work Ethic among Welfare Recipients, Welfare Recipients in Training Programs, and Employed Past Welfare Recipients.

ERIC Educational Resources Information Center

Tang, Thomas Li-Ping; Smith-Brandon, Vancie L.

2001-01-01

Work-related attitudes of 164 welfare recipients, 159 recipients in job training, and 158 employed former recipients were compared. Those employed had the highest scores in money ethic, work ethic, and self-esteem; higher education and income; and longer job tenure. Recipients not in training had the least positive money and work ethic. (Contains…

Biotin status affects nickel allergy via regulation of interleukin-1beta production in mice.

PubMed

Kuroishi, Toshinobu; Kinbara, Masayuki; Sato, Naoki; Tanaka, Yukinori; Nagai, Yasuhiro; Iwakura, Yoichiro; Endo, Yasuo; Sugawara, Shunji

2009-05-01

Biotin, a water-soluble B complex vitamin, is possibly involved in chronic inflammatory diseases, although the detailed mechanisms are unclear. In this study, we investigated the effects of biotin status on nickel (Ni) allergy in mice. Mice were fed a basal or biotin-deficient (BD) diet for 8 wk and sensitized with an intraperitoneal injection of NiCl(2) and lipopolysaccharide. Ten days after sensitization, NiCl(2) was intradermally injected into pinnas and ear swelling was measured. For in vitro analysis, we cultured a murine macrophage cell line, J774.1, under a biotin-sufficient (C, meaning control) or BD condition for 4 wk and analyzed interleukin (IL)-1 production. Significantly higher ear swelling was induced in BD mice than C mice. Adaptive transfer of splenocytes from both C and BD mice induced Ni allergy in unsensitized mice. Regardless of donor mice, ear swelling was significantly higher in BD recipient mice than C recipient mice. Ni allergy was not induced in either C or BD IL-1(-/-) mice. Splenocytes from BD mice produced a significantly higher amount of IL-1beta than those from C mice. Production and mRNA expression of IL-1beta were significantly higher in BD J774.1 cells than in C cells. Biotin supplementation inhibited the augmentation of IL-1beta production in vitro. In vivo supplementation of biotin in drinking water dose-dependently decreased ear swelling in C and BD mice. These results indicate that biotin status affects Ni allergy in the elicitation phase via the upregulation of IL-1beta production in mice, suggesting that biotin supplementation may have therapeutic effects on human metal allergy.

10 CFR 603.510 - Recipient qualifications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Evaluation Recipient Qualification § 603.510 Recipient qualifications. Prior to award of a TIA, the... for awarding a grant or cooperative agreement. If the recipient is a consortium that is not formally... 10 Energy 4 2014-01-01 2014-01-01 false Recipient qualifications. 603.510 Section 603.510 Energy...

10 CFR 603.510 - Recipient qualifications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Evaluation Recipient Qualification § 603.510 Recipient qualifications. Prior to award of a TIA, the... for awarding a grant or cooperative agreement. If the recipient is a consortium that is not formally... 10 Energy 4 2011-01-01 2011-01-01 false Recipient qualifications. 603.510 Section 603.510 Energy...

10 CFR 603.510 - Recipient qualifications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Evaluation Recipient Qualification § 603.510 Recipient qualifications. Prior to award of a TIA, the... for awarding a grant or cooperative agreement. If the recipient is a consortium that is not formally... 10 Energy 4 2012-01-01 2012-01-01 false Recipient qualifications. 603.510 Section 603.510 Energy...

CD27/CD70, CD134/CD134 ligand, and CD30/CD153 pathways are independently essential for generation of regulatory cells after intratracheal delivery of alloantigen.

PubMed

Aramaki, Osamu; Shirasugi, Nozomu; Akiyama, Yoshinobu; Shibutani, Shintaro; Takayama, Tadatoshi; Shimazu, Motohide; Kitajima, Masaki; Ikeda, Yoshifumi; Okumura, Ko; Yagita, Hideo; Niimi, Masanori

2003-09-15

We investigated whether blockade of tumor necrosis factor receptor-ligand pathways could generate regulatory cells induced by intratracheal delivery of alloantigen. CBA (H-2k) mice were pretreated with intratracheal delivery of splenocytes (1x10(7)) from C57BL/10 (H-2b) mice and intraperitoneal administration of monoclonal antibody (mAb) specific for CD70, CD134 ligand (CD134L), CD153, or CD137L. Seven days later, C57BL/10 hearts were transplanted into pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes (5x10(7)) from pretreated CBA mice and transplantation of a C57BL/10 heart on the same day. Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST] 12 days). Pretreatment with intratracheal delivery of C57BL/10 donor splenocytes prolonged graft survival significantly (MST 84 days). Mice given intratracheal delivery of alloantigen plus anti-CD70, anti-CD134L, or anti-CD153 mAb, but not those given intratracheal delivery of alloantigen plus anti-CD137L mAb, rejected their graft acutely (MST 16, 14, 10, and 65 days, respectively). Adoptive transfer of splenocytes from mice pretreated with intratracheal delivery of alloantigen plus anti-CD70, CD134L, or CD153 mAb did not prolong survival of C57BL/10 cardiac grafts in naive secondary CBA recipients (MST 14, 11, and 11 days, respectively), whereas adoptive transfer of splenocytes from mice given intratracheal delivery of alloantigen plus anti-CD137L mAb did (MST 75 days). The CD27/CD70, CD134/CD134L, and CD30/CD153 pathways are independently required for generation of regulatory cells in our model.

29 CFR 94.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Recipient. 94.660 Section 94.660 Labor Office of the... § 94.660 Recipient. Recipient means any individual, corporation, partnership, association, unit of government (except a Federal agency) or legal entity, however organized, that receives an award directly from...

Children's Conceptions of Mental Illness: A Naive Theory Approach

ERIC Educational Resources Information Center

Fox, Claudine; Buchanan-Barrow, Eithne; Barrett, Martyn

2010-01-01

This paper reports two studies that investigated children's conceptions of mental illness using a naive theory approach, drawing upon a conceptual framework for analysing illness representations which distinguishes between the identity, causes, consequences, curability, and timeline of an illness. The studies utilized semi-structured interviewing…

Mathematical Model of Naive T Cell Division and Survival IL-7 Thresholds.

PubMed

Reynolds, Joseph; Coles, Mark; Lythe, Grant; Molina-París, Carmen

2013-01-01

We develop a mathematical model of the peripheral naive T cell population to study the change in human naive T cell numbers from birth to adulthood, incorporating thymic output and the availability of interleukin-7 (IL-7). The model is formulated as three ordinary differential equations: two describe T cell numbers, in a resting state and progressing through the cell cycle. The third is introduced to describe changes in IL-7 availability. Thymic output is a decreasing function of time, representative of the thymic atrophy observed in aging humans. Each T cell is assumed to possess two interleukin-7 receptor (IL-7R) signaling thresholds: a survival threshold and a second, higher, proliferation threshold. If the IL-7R signaling strength is below its survival threshold, a cell may undergo apoptosis. When the signaling strength is above the survival threshold, but below the proliferation threshold, the cell survives but does not divide. Signaling strength above the proliferation threshold enables entry into cell cycle. Assuming that individual cell thresholds are log-normally distributed, we derive population-average rates for apoptosis and entry into cell cycle. We have analyzed the adiabatic change in homeostasis as thymic output decreases. With a parameter set representative of a healthy individual, the model predicts a unique equilibrium number of T cells. In a parameter range representative of persistent viral or bacterial infection, where naive T cell cycle progression is impaired, a decrease in thymic output may result in the collapse of the naive T cell repertoire.

Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector.

PubMed

Dardalhon, V; Jaleco, S; Rebouissou, C; Ferrand, C; Skander, N; Swainson, L; Tiberghien, P; Spits, H; Noraz, N; Taylor, N

2000-08-01

Retroviral vectors based on the Moloney murine leukemia virus (MuLV) have become the primary tool for gene delivery into hematopoietic cells, but clinical trials have been hampered by low transduction efficiencies. Recently, we and others have shown that gene transfer of MuLV-based vectors into T cells can be significantly augmented using a fibronectin-facilitated protocol. Nevertheless, the relative abilities of naive (CD45RA(+)) and memory (CD45RO(+)) lymphocyte subsets to be transduced has not been assessed. Although naive T cells demonstrate a restricted cytokine profile following antigen stimulation and a decreased susceptibility to infection with human immunodeficiency virus, it was not clear whether they could be efficiently infected with a MuLV vector. This study describes conditions that permitted gene transfer of an enhanced green fluorescent protein-expressing retroviral vector in more than 50% of naive umbilical cord (UC) blood and peripheral blood (PB) T cells following CD3/CD28 ligation. Moreover, treatment of naive T cells with interleukin-7 resulted in the maintenance of a CD45RA phenotype and gene transfer levels approached 20%. Finally, it was determined that parameters for optimal transduction of CD45RA(+) T cells isolated from PB and UC blood differed: transduction of the UC cells was significantly increased by the presence of autologous mononuclear cells (24.5% versus 56.5%). Because naive T cells harbor a receptor repertoire that allows them to respond to novel antigens, the development of protocols targeting their transduction is crucial for gene therapy applications. This approach will also allow the functions of exogenous genes to be evaluated in primary nontransformed naive T cells.

Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

PubMed

Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

2017-02-01

Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Naive vs. Sophisticated Methods of Forecasting Public Library Circulations.

ERIC Educational Resources Information Center

Brooks, Terrence A.

1984-01-01

Two sophisticated--autoregressive integrated moving average (ARIMA), straight-line regression--and two naive--simple average, monthly average--forecasting techniques were used to forecast monthly circulation totals of 34 public libraries. Comparisons of forecasts and actual totals revealed that ARIMA and monthly average methods had smallest mean…

Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes.

PubMed

Nikoopour, Enayat; Schwartz, Jordan A; Huszarik, Katrina; Sandrock, Christian; Krougly, Olga; Lee-Chan, Edwin; Singh, Bhagirath

2010-05-01

IL-17-producing T cells are regarded as potential pathogenic T cells in the induction of autoimmune diseases. Previously, we have shown that injection of adjuvants containing Mycobacterium, such as CFA or bacillus Calmette-Guérin, can prevent type 1 diabetes in NOD mice. We injected NOD mice with mycobacterial products s.c. and analyzed the IL-17-producing cells from the draining lymph nodes and spleen by restimulating whole-cell populations or CD4(+) T cells in vitro with or without IL-17-polarizing cytokines. Mice receiving CFA had a concomitant rise in the level of IL-17, IL-22, IL-10, and IFN-gamma in the draining lymph node and spleen. Adoptive transfer of splenocytes from CFA-injected NOD mice polarized with TGF-beta plus IL-6 or IL-23 delayed the development of diabetes in recipient mice. IL-17-producing cells induced by CFA maintained their IL-17-producing ability in the recipient mice. Injection of CFA also changed the cytokine profile of cells in pancreatic tissue by increasing IL-17, IL-10, and IFN-gamma cytokine gene expression. We suggest that the rise in the level of IL-17 after adjuvant therapy in NOD mice has a protective effect on type 1 diabetes development.

Administration of hydrogen-rich saline in mice with allogeneic hematopoietic stem-cell transplantation.

PubMed

Yuan, Lijuan; Chen, Xiaoping; Qian, Liren; Shen, Jianliang; Cai, Jianming

2015-03-12

Hydrogen, as a novel antioxidant, has been shown to selectively reduce the level of hydroxyl radicals and alleviate acute oxidative stress in many animal experiments. Hydrogen-rich saline provides a high concentration of hydrogen that can be easily and safely applied. Allogeneic hematopoietic stem-cell transplantation (HSCT) has been the most curative therapy for hematological malignancies. However, acute graft-versus-host disease (aGVHD) is the main cause of death in post-transplantation patients. In this study, we examined whether hydrogen-rich saline would show favorable effects on acute GVHD in mice. After lethal irradiation, BALB/c mice received bone marrow transplantation from C57BL/6 mice. Hydrogen-rich saline (5 ml/kg) was given to recipient mice in the hydrogen group once a day by intraperitoneal injection, and saline (5 ml/kg) was given to recipient mice in the saline group. Survival rates were monitored, clinical and pathological scores of aGVHD were determined after bone marrow transplantation (BMT), and the serum cytokine levels were examined on the 7th day after BMT. This study proves that hydrogen-rich saline increased the survival rate, reduced clinical and histopathological scores of aGVHD, promoted the recovery of white blood cells, reduced the serum cytokine levels, and reversed tissue damage after transplantation in mice. Hydrogen has potential as an effective and safe therapeutic agent in aGVHD.

Development of a novel mouse glioma model using lentiviral vectors

PubMed Central

Marumoto, Tomotoshi; Tashiro, Ayumu; Friedmann-Morvinski, Dinorah; Scadeng, Miriam; Soda, Yasushi; Gage, Fred H; Verma, Inder M

2009-01-01

We report the development of a new method to induce glioblastoma multiforme in adult immunocompetent mice by injecting Cre-loxP–controlled lentiviral vectors expressing oncogenes. Cell type- or region-specific expression of activated forms of the oncoproteins Harvey-Ras and AKT in fewer than 60 glial fibrillary acidic protein–positive cells in the hippocampus, subventricular zone or cortex of mice heterozygous for the gene encoding the tumor suppressor Tp53 were tested. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. However, tumors were rarely detected when the mice were transduced in the cortex. Transplantation of brain tumor cells into naive recipient mouse brain resulted in the formation of glioblastoma multiforme–like tumors, which contained CD133+ cells, formed tumorspheres and could differentiate into neurons and astrocytes. We suggest that the use of Cre-loxP–controlled lentiviral vectors is a novel way to generate a mouse glioblastoma multiforme model in a region- and cell type-specific manner in adult mice. PMID:19122659

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

PubMed Central

Dumas, Eric K.; Gross, Timothy; Larabee, Jason; Pate, Lance; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J. M.; Collins, Limone C.; Spooner, Christina E.; Chen, Hua; Ballard, Jimmy; James, Judith A.

2017-01-01

ABSTRACT Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n = 33) versus anthrax vaccine adsorbed (AVA; n = 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines. PMID:28877928

Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

PubMed Central

Yang, Yinhua; An, Jie; Weng, Nan-ping

2008-01-01

IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells. PMID:18322183

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

PubMed

Helmi, Mohamed; Love, Robert B; Welter, Debbie; Cornwell, Richard D; Meyer, Keith C

2003-03-01

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. A university hospital. Lung transplant recipients with CF or other indications for transplantation. None. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect

10 CFR 603.510 - Recipient qualifications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Recipient qualifications. 603.510 Section 603.510 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business Evaluation Recipient Qualification § 603.510 Recipient qualifications. Prior to award of a TIA, the...

10 CFR 600.141 - Recipient responsibilities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Nonprofit Organizations Post-Award Requirements § 600.141 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to DOE regarding the settlement... 10 Energy 4 2012-01-01 2012-01-01 false Recipient responsibilities. 600.141 Section 600.141 Energy...

10 CFR 600.141 - Recipient responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Nonprofit Organizations Post-Award Requirements § 600.141 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to DOE regarding the settlement... 10 Energy 4 2011-01-01 2011-01-01 false Recipient responsibilities. 600.141 Section 600.141 Energy...

10 CFR 600.141 - Recipient responsibilities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Nonprofit Organizations Post-Award Requirements § 600.141 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to DOE regarding the settlement... 10 Energy 4 2013-01-01 2013-01-01 false Recipient responsibilities. 600.141 Section 600.141 Energy...

10 CFR 600.141 - Recipient responsibilities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Nonprofit Organizations Post-Award Requirements § 600.141 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to DOE regarding the settlement... 10 Energy 4 2014-01-01 2014-01-01 false Recipient responsibilities. 600.141 Section 600.141 Energy...

10 CFR 603.510 - Recipient qualifications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Recipient qualifications. 603.510 Section 603.510 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business Evaluation Recipient Qualification § 603.510 Recipient qualifications. Prior to award of a TIA, the...

Diagnosis of combined faults in Rotary Machinery by Non-Naive Bayesian approach

NASA Astrophysics Data System (ADS)

Asr, Mahsa Yazdanian; Ettefagh, Mir Mohammad; Hassannejad, Reza; Razavi, Seyed Naser

2017-02-01

When combined faults happen in different parts of the rotating machines, their features are profoundly dependent. Experts are completely familiar with individuals faults characteristics and enough data are available from single faults but the problem arises, when the faults combined and the separation of characteristics becomes complex. Therefore, the experts cannot declare exact information about the symptoms of combined fault and its quality. In this paper to overcome this drawback, a novel method is proposed. The core idea of the method is about declaring combined fault without using combined fault features as training data set and just individual fault features are applied in training step. For this purpose, after data acquisition and resampling the obtained vibration signals, Empirical Mode Decomposition (EMD) is utilized to decompose multi component signals to Intrinsic Mode Functions (IMFs). With the use of correlation coefficient, proper IMFs for feature extraction are selected. In feature extraction step, Shannon energy entropy of IMFs was extracted as well as statistical features. It is obvious that most of extracted features are strongly dependent. To consider this matter, Non-Naive Bayesian Classifier (NNBC) is appointed, which release the fundamental assumption of Naive Bayesian, i.e., the independence among features. To demonstrate the superiority of NNBC, other counterpart methods, include Normal Naive Bayesian classifier, Kernel Naive Bayesian classifier and Back Propagation Neural Networks were applied and the classification results are compared. An experimental vibration signals, collected from automobile gearbox, were used to verify the effectiveness of the proposed method. During the classification process, only the features, related individually to healthy state, bearing failure and gear failures, were assigned for training the classifier. But, combined fault features (combined gear and bearing failures) were examined as test data. The achieved

Effect of developmental stage of HSC and recipient on transplant outcomes

PubMed Central

Arora, Natasha; Wenzel, Pamela L.; McKinney-Freeman, Shannon L.; Ross, Samantha J.; Kim, Peter G.; Chou, Stephanie S.; Yoshimoto, Momoko; Yoder, Mervin C.; Daley, George Q.

2014-01-01

Summary The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aortagonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage there is a discrepancy between the apparent frequency of HSCs suggested by imaging and their rarity when measured by limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver (FL) or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs. PMID:24914562

Comparison of Naive Bayes and Decision Tree on Feature Selection Using Genetic Algorithm for Classification Problem

NASA Astrophysics Data System (ADS)

Rahmadani, S.; Dongoran, A.; Zarlis, M.; Zakarias

2018-03-01

This paper discusses the problem of feature selection using genetic algorithms on a dataset for classification problems. The classification model used is the decicion tree (DT), and Naive Bayes. In this paper we will discuss how the Naive Bayes and Decision Tree models to overcome the classification problem in the dataset, where the dataset feature is selectively selected using GA. Then both models compared their performance, whether there is an increase in accuracy or not. From the results obtained shows an increase in accuracy if the feature selection using GA. The proposed model is referred to as GADT (GA-Decision Tree) and GANB (GA-Naive Bayes). The data sets tested in this paper are taken from the UCI Machine Learning repository.

Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

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

Lin, Gu-Jiun; Sytwu, Huey-Kang; Yu, Jyh-Cherng

Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO inmore » the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs.« less

45 CFR 1638.5 - Recipient policies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies. 1638.5 Section 1638.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON SOLICITATION § 1638.5 Recipient policies. Each recipient shall adopt written policies to implement the...

45 CFR 1632.4 - Recipient policies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Recipient policies. 1632.4 Section 1632.4 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION REDISTRICTING § 1632.4 Recipient policies. Each recipient shall adopt written policies to implement the requirements of...

45 CFR 1632.4 - Recipient policies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies. 1632.4 Section 1632.4 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION REDISTRICTING § 1632.4 Recipient policies. Each recipient shall adopt written policies to implement the requirements of...

Sex differences in colonization of gut microbiota from a man with short-term vegetarian and inulin-supplemented diet in germ-free mice.

PubMed

Wang, Jing-Jing; Wang, Jing; Pang, Xiao-Yan; Zhao, Li-Ping; Tian, Ling; Wang, Xing-Peng

2016-10-31

Gnotobiotic mouse model is generally used to evaluate the efficacy of gut microbiota. Sex differences of gut microbiota are acknowledged, yet the effect of recipient's gender on the bacterial colonization remains unclear. Here we inoculated male and female germ-free C57BL/6J mice with fecal bacteria from a man with short-term vegetarian and inulin-supplemented diet. We sequenced bacterial 16S rRNA genes V3-V4 region from donor's feces and recipient's colonic content. Shannon diversity index showed female recipients have higher bacteria diversity than males. Weighted UniFrac principal coordinates analysis revealed the overall structures of male recipient's gut microbiota were significantly separated from those of females, and closer to the donor. Redundancy analysis identified 46 operational taxonomic units (OTUs) differed between the sexes. The relative abundance of 13 OTUs were higher in males, such as Parabacteroides distasonis and Blautia faecis, while 33 OTUs were overrepresented in females, including Clostridium groups and Escherichia fergusonii/Shigella sonnei. Moreover, the interactions of these differential OTUs were sexually distinct. These findings demonstrated that the intestine of male and female mice preferred to accommodate microbiota differently. Therefore, it is necessary to designate the gender of gnotobiotic mice for complete evaluation of modulatory effects of gut microbiota from human feces upon diseases.

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.

PubMed

Gossel, Graeme; Hogan, Thea; Cownden, Daniel; Seddon, Benedict; Yates, Andrew J

2017-03-10

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

5 CFR 1315.15 - Grant recipients.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Grant recipients. 1315.15 Section 1315.15 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.15 Grant recipients. Recipients of Federal assistance may pay interest penalties if so specified in their contracts with...

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice

PubMed Central

Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F.

2011-01-01

The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg−1 and (v) 2.00 g kg−1 black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23–27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities. PMID:18955369

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.

PubMed

Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F

2011-01-01

The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg(-1) and (v) 2.00 g kg(-1) black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23-27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities.

Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption.

PubMed

Chandrasekaran, Jeyamala; Thiruvengadam, S J

2015-01-01

Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security.

Naive (commonsense) geography and geobrowser usability after ten years of Google Earth

NASA Astrophysics Data System (ADS)

Hamerlinck, J. D.

2016-04-01

In 1995, the concept of ‘naive geography’ was formally introduced as an area of cognitive geographic information science representing ‘the body of knowledge that people have about the surrounding geographic world’ and reflecting ‘the way people think and reason about geographic space and time, both consciously and subconsciously’. The need to incorporate such commonsense knowledge and reasoning into design of geospatial technologies was identified but faced challenges in formalizing these relationships and processes in software implementation. Ten years later, the Google Earth geobrowser was released, marking the beginning of a new era of open access to, and application of, geographic data and information in society. Fast-forward to today, and the opportunity presents itself to take stock of twenty years of naive geography and a decade of the ubiquitous virtual globe. This paper introduces an ongoing research effort to explore the integration of naive (or commonsense) geography concepts in the Google Earth geobrowser virtual globe and their possible impact on Google Earth's usability, utility, and usefulness. A multi-phase methodology is described, combining usability reviews and usability testing with use-case scenarios involving the U.S.-Canadian Yellowstone to Yukon Initiative. Initial progress on a usability review combining cognitive walkthroughs and heuristics evaluation is presented.

Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption

PubMed Central

Chandrasekaran, Jeyamala; Thiruvengadam, S. J.

2015-01-01

Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security. PMID:26550603

Three Naive Questions: Addressed to the Modern Educational Optimism

ERIC Educational Resources Information Center

Krstic, Predrag

2016-01-01

This paper aims to question anew the popular and supposedly self-evident affirmation of education, in its modern incarnation as in its historical notion. The "naive" questions suggest that we have recently taken for granted that education ought to be for the masses, that it ought to be upbringing, and that it is better than ignorance.…

Targeting Antigens to Dec-205 on Dendritic Cells Induces Immune Protection in Experimental Colitis in Mice

PubMed Central

Wadwa, Munisch; Klopfleisch, Robert; Buer, Jan; Westendorf, Astrid M.

2016-01-01

The endocytotic c-type lectin receptor DEC-205 is highly expressed on immature dendritic cells. In previous studies, it was shown that antigen-targeting to DEC-205 is a useful tool for the induction of antigen-specific Foxp3+ regulatory T cells and thereby can prevent inflammatory processes. However, whether this approach is sufficient to mediate tolerance in mucosal tissues like the gut is unknown. In this study, we established a new mouse model in which the adoptive transfer of naive hemagglutinin (HA)-specific CD4+Foxp3– T cells into VILLIN-HA transgenic mice leads to severe colitis. To analyze if antigen-targeting to DEC-205 could protect against inflammation of the gut, VILLIN-HA transgenic mice were injected with an antibody–antigen complex consisting of the immunogenic HA110–120 peptide coupled to an α-DEC-205 antibody (DEC-HA) before adoptive T cell transfer. DEC-HA-treated mice showed significantly less signs of intestinal inflammation as was demonstrated by reduced loss of body weight and histopathology in the gut. Strikingly, abrogated intestinal inflammation was mediated via the conversion of naive HA-specific CD4+Foxp3– T cells into HA-specific CD4+Foxp3+ regulatory T cells. In this study, we provide evidence that antigen-targeting to DEC-205 can be utilized for the induction of tolerance in mucosal organs that are confronted with large numbers of exogenous antigens. PMID:27141310

Viral infections in transplant recipients.

PubMed

Razonable, R R; Eid, A J

2009-12-01

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

PubMed

Mwangi, Timothy K; Berke, Ian M; Nieves, Eduardo H; Bell, Richard D; Adams, Samuel B; Setton, Lori A

2018-05-26

Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a

The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

PubMed Central

Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

2016-01-01

Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

PubMed

Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

Adoptive cell transfer of resistance to Mycobacterium leprae infections in mice.

PubMed Central

Lowe, C; Brett, S J; Rees, R J

1985-01-01

Cells were transferred from mice intradermally vaccinated with killed Mycobacterium leprae to sublethally irradiated recipients. Unseparated cells from lymph nodes or spleens of M. leprae vaccinated mice were found to cause significant inhibition of the growth of a subsequent M. leprae challenge in mouse footpads for up to 26 weeks after vaccination. Vaccination with live BCG and cells transferred from BCG-vaccinated mice caused no significant inhibition of M. leprae growth in mouse footpads. Cell separation into fractions containing predominantly B and T lymphocytes showed that the inhibition of growth was due to M. leprae-sensitized T lymphocytes. M. leprae vaccinated mice were also skin tested with soluble M. leprae antigen and showed maximum delayed hypersensitivity responses 4 weeks after vaccination. PMID:3876183

Multiple ovarian transplants to rescue a transgenic line of mice.

PubMed

Dawes, Joyce; Liu, Bowen; Mars, Wendy; Michalopoulos, George; Khillan, Jaspal S

2010-06-01

Transgenic mice are useful tools for studying gene function and regulation but can be difficult to successfully breed. To 'rescue' transgenic lines that are difficult to propagate, researchers use a variety of techniques. One method is ovarian transplant, in which researchers remove ovaries from a donor transgenic mouse, cryopreserve the ovarian tissue, transplant this tissue into histocompatible female mice and breed these recipient females. Though it is a useful technique, cryopreservation can potentially damage ovarian tissue, which could reduce fertility. In this article, the authors describe how they carried out ovarian transplants without cryopreservation to rescue a line of transgenic C57BL/6 mice. Other researchers who have experience with mouse reproductive surgery should be able to use this technique to rescue infertile transgenic lines of mice.

The Effect of Social Comparability between Donor and Recipient on Recipient’s Reactions to Aid.

DTIC Science & Technology

The results indicate that receiving aid from a social comparison other had a negative effect on the recipient’s situational self - esteem and self ...and hence a threat to self - esteem , when aid is given by a social comparison other. (Author Modified Abstract)...The study explored the effect of social comparability between the donor and the recipient on the recipient’s self -perception and his perception of

Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization.

PubMed

Coffin, S E; Clark, S L; Bos, N A; Brubaker, J O; Offit, P A

1999-09-15

Parenterally administered immunizations have long been used to induce protection from mucosal pathogens such as Bordetella pertussis and influenza virus. We previously found that i.m. inoculation of mice with the intestinal pathogen, rotavirus, induced virus-specific Ab production by intestinal lymphocytes. We have now used adoptive transfer studies to identify the cell types responsible for the generation of virus-specific Ab production by gut-associated lymphoid tissue (GALT) after i.m. immunization. Three days after i.m. immunization with rotavirus, cells obtained from the draining peripheral lymph nodes of donor mice were transferred into naive recipient mice. We found that intestinal lymphocytes produced rotavirus-specific Igs (IgM, IgA, and IgG) 2 wk after transfer of either unfractionated cells, or unfractionated cells rendered incapable of cellular division by mitomycin C treatment. Additional studies demonstrated that rotavirus-specific IgA, but not IgG, was produced by intestinal lymphocytes after transfer of purified B cells. Ig allotype analysis revealed that rotavirus-specific IgA was produced by intestinal B cells of recipient origin, suggesting that migration of Ag-presenting B cells from peripheral lymphoid tissues to GALT may contribute to the generation of mucosal IgA responses after parenteral immunization. Strategies that promote Ag uptake and presentation by B cells may enhance mucosal IgA production following parenteral immunization.

Expert and Naive Raters Using the PAG: Does it Matter?

ERIC Educational Resources Information Center

Cornelius, Edwin T.; And Others

1984-01-01

Questions the observed correlation between job experts and naive raters using the Position Analysis Questionnaire (PAQ); and conducts a replication of the Smith and Hakel study (1979) with college students (N=39). Concluded that PAQ ratings from job experts and college students are not equivalent and therefore are not interchangeable. (LLL)

Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice

PubMed Central

Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.

2013-01-01

Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DCs). Co-culture of CD4+ T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of Th-1 type cytokines that was ameliorated when the DCs were obtained from GSPs-fed mice; whereas, DCs obtained from GSPs-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4, dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. PMID:23321928

Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

PubMed

Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

2016-01-01

The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells.

Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

PubMed

Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

2012-11-30

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

14 CFR 1252.300 - General responsibilities of recipients.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false General responsibilities of recipients. 1252.300 Section 1252.300 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... Responsibilities of Recipients § 1252.300 General responsibilities of recipients. Each NASA recipient must ensure...

43 CFR 17.337 - Remedial action by recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Investigation, Conciliation, and Enforcement Procedures § 17.337 Remedial action by recipients. Where DOI finds... DOI may require to overcome the effects of the discrimination. If another recipient exercises control over the recipient that has discriminated, DOI may require both recipients to take remedial action. ...

43 CFR 17.337 - Remedial action by recipients.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Investigation, Conciliation, and Enforcement Procedures § 17.337 Remedial action by recipients. Where DOI finds... DOI may require to overcome the effects of the discrimination. If another recipient exercises control over the recipient that has discriminated, DOI may require both recipients to take remedial action. ...

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

PubMed Central

Gossel, Graeme; Hogan, Thea; Cownden, Daniel

2017-01-01

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment. DOI: http://dx.doi.org/10.7554/eLife.23013.001 PMID:28282024

Thinking Process of Naive Problem Solvers to Solve Mathematical Problems

ERIC Educational Resources Information Center

Mairing, Jackson Pasini

2017-01-01

Solving problems is not only a goal of mathematical learning. Students acquire ways of thinking, habits of persistence and curiosity, and confidence in unfamiliar situations by learning to solve problems. In fact, there were students who had difficulty in solving problems. The students were naive problem solvers. This research aimed to describe…

The Profession of Psychology Scale: Sophisticated and Naive Students' Responses

ERIC Educational Resources Information Center

Rosenthal, Gary T.; Soper, Barlow; Rachal, Chris; McKnight, Richard R.; Price, A. W.

2004-01-01

The Profession of Psychology Scale (Rosenthal, McKnight & Price, 2001) was used to investigate whether taking more psychology courses results in a more accurate understanding of what is required to become a psychologist. Data indicate that though misconceptions exist in both Naive students (those who had not completed any psychology courses) and…

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps.

PubMed

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John; Vreugde, Sarah

2018-01-01

Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP.

Agmatine blocks ethanol-induced locomotor hyperactivity in male mice.

PubMed

Ozden, Onder; Kayir, Hakan; Ozturk, Yusuf; Uzbay, Tayfun

2011-05-20

Ethanol-induced locomotor activity is associated to rewarding effects of ethanol and ethanol dependence. Agmatine is a novel endogenous ligand at α2-adrenoceptors, imidazoline and N-methyl-d-aspartate (NMDA) receptors, as well as a nitric oxide synthase (NOS) inhibitor. There is no evidence presented for the relationship between the acute locomotor stimulating effect of ethanol and agmatine. Thus, the present study investigated the effects of agmatine on acute ethanol-induced locomotor hyperactivity in mice. Adult male Swiss-Webster mice (26-36g) were used as subjects. Locomotor activity of the mice was recorded for 30min immediately following intraperitoneal administration of ethanol (0.5, 1 and 2g/kg) or saline (n=8 for each group). Agmatine (5, 10 and 20mg/kg) or saline was administered intraperitoneally to another four individual groups (n=8 for each group) of the mice 20min before the ethanol injection. In these groups, locomotor activity was also recorded immediately following ethanol (0.5g/kg) injection for 30min. Ethanol (0.5g/kg) produced some significant increases in locomotor activity of the mice. Agmatine (5-20mg/kg) significantly blocked the ethanol (0.5g/kg)-induced locomotor hyperactivity. These doses of agmatine did not affect the locomotor activity in naive mice when they were administered alone. Our results suggest that agmatine has an important role in ethanol-induced locomotor hyperactivity in mice. There may be a relationship between the addictive psychostimulant effects of the ethanol and central agmatinergic system. Copyright © 2011 Elsevier B.V. All rights reserved.

Toll-like receptor 4-positive macrophages protect mice from Pasteurella pneumotropica-induced pneumonia

NASA Technical Reports Server (NTRS)

Hart, Marcia L.; Mosier, Derek A.; Chapes, Stephen K.

2003-01-01

This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4(Lps-del) mouse strains C57BL10/ScN (B10) and STOCK Abb(tm1) TLR4(Lps-del) Slc11a1(s)(B10 x C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4(Lps-del) genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 x C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 x C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 x C2D mice, and there was earlier transcription of KC and MIP-1alpha in B10 x C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 x C2D mice, which lack CD4(+) T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.

Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice

PubMed Central

Tsang, Julia Yuen-Shan; Tanriver, Yakup; Jiang, Shuiping; Xue, Shao-An; Ratnasothy, Kulachelvy; Chen, Daxin; Stauss, Hans J.; Bucy, R. Pat; Lombardi, Giovanna; Lechler, Robert

2008-01-01

T cell responses to MHC-mismatched transplants can be mediated via direct recognition of allogeneic MHC molecules on the cells of the transplant or via recognition of allogeneic peptides presented on the surface of recipient APCs in recipient MHC molecules — a process known as indirect recognition. As CD4+CD25+ Tregs play an important role in regulating alloresponses, we investigated whether mouse Tregs specific for allogeneic MHC molecules could be generated in vitro and could promote transplantation tolerance in immunocompetent recipient mice. Tregs able to directly recognize allogeneic MHC class II molecules (dTregs) were obtained by stimulating CD4+CD25+ cells from C57BL/6 mice (H-2b) with allogeneic DCs from BALB/c mice (H-2d). To generate Tregs that indirectly recognized allogeneic MHC class II molecules, dTregs were retrovirally transduced with TCR genes conferring specificity for H-2Kd presented by H-2Ab MHC class II molecules. The dual direct and indirect allospecificity of the TCR-transduced Tregs was confirmed in vitro. In mice, TCR-transduced Tregs, but not dTregs, induced long-term survival of partially MHC-mismatched heart grafts when combined with short-term adjunctive immunosuppression. Further, although dTregs were only slightly less effective than TCR-transduced Tregs at inducing long-term survival of fully MHC-mismatched heart grafts, histologic analysis of long-surviving hearts demonstrated marked superiority of the TCR-transduced Tregs. Thus, Tregs specific for allogeneic MHC class II molecules are effective in promoting transplantation tolerance in mice, which suggests that such cells have clinical potential. PMID:18846251

Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice

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

Gao Xiaodong; Song Lujun; Shen Kuntang

2008-06-20

The transplantation of bone marrow (BM) derived cells to initiate pancreatic regeneration is an attractive but as-yet unrealized strategy. Presently, BM derived cells from green fluorescent protein transgenic mice were transplanted into diabetic mice. Repair of diabetic islets was evidenced by reduction of hyperglycemia, increase in number of islets, and altered pancreatic histology. Cells in the pancreata of recipient mice co-expressed BrdU and insulin. Double staining revealed {beta} cells were in the process of proliferation. BrdU{sup +} insulin{sup -} PDX-1{sup +} cells, Ngn3{sup +} cells and insulin{sup +} glucagon{sup +} cells, which showed stem cells, were also found during {beta}-cellmore » regeneration. The majority of transplanted cells were mobilized to the islet and ductal regions. In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. It is concluded that BM derived cells especially CD34{sup +} cells can promote repair of pancreatic islets. Moreover, both proliferation of {beta} cells and differentiation of pancreatic stem cells contribute to the regeneration of {beta} cells.« less

A Workshop for High School Students on Naive Set Theory

ERIC Educational Resources Information Center

Wegner, Sven-Ake

2014-01-01

In this article we present the prototype of a workshop on naive set theory designed for high school students in or around the seventh year of primary education. Our concept is based on two events which the author organized in 2006 and 2010 for students of elementary school and high school, respectively. The article also includes a practice report…

Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system.

PubMed

Zhang, Q; Ichimaru, N; Higuchi, S; Cai, S; Hou, J; Fujino, M; Nonomura, N; Kobayashi, M; Ando, H; Uno, A; Sakurai, K; Mochizuki, S; Adachi, Y; Ohno, N; Zou, H; Xu, J; Li, X-K; Takahara, S

2015-03-01

The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We developed a novel small interfering RNA (siRNA) delivery system with a poly-dA extension at the 5'-end of the siRNA sense strand that was stably incorporated into 1,3-β-glucan (schizophyllan, SPG). This was captured and incorporated into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA mice permanently accepted B10 fully mismatched cardiac allografts. Consistent with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen. In addition, naive CBA recipients given an adoptive transfer of splenocytes from the primary recipients with siCD40/SPG accepted a heart graft from donor-type B10, but not third-party Balb/c mice. In conclusion, the treatment with siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the permanent acceptance of mouse cardiac allografts. These findings have important implications for clarifying the mechanism underlying the induction of tolerance in DCs, and also highlight the potential of immunomodulation and the feasibility of siRNA-based clinical therapy in the transplantation field.

Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice.

PubMed

Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A; Xu, Hui; Katiyar, Santosh K

2013-03-01

Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T-cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DC). Co-culture of CD4(+) T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of T-helper (TH) 1-type cytokines that was ameliorated when the DCs were obtained from GSP-fed mice, whereas DCs obtained from GSP-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4,-dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. Cancer Prev Res; 6(3); 242-52. ©2013 AACR. ©2013 AACR.

32 CFR 21.675 - Recipient.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Recipient. 21.675 Section 21.675 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.675 Recipient. An organization or other entity...

32 CFR 21.675 - Recipient.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Recipient. 21.675 Section 21.675 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.675 Recipient. An organization or other entity...

32 CFR 21.675 - Recipient.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Recipient. 21.675 Section 21.675 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.675 Recipient. An organization or other entity...

32 CFR 21.675 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Recipient. 21.675 Section 21.675 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.675 Recipient. An organization or other entity...

32 CFR 21.675 - Recipient.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Recipient. 21.675 Section 21.675 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.675 Recipient. An organization or other entity...

Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.

PubMed

Staley, Christopher; Kaiser, Thomas; Beura, Lalit K; Hamilton, Matthew J; Weingarden, Alexa R; Bobr, Aleh; Kang, Johnthomas; Masopust, David; Sadowsky, Michael J; Khoruts, Alexander

2017-08-01

Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable. Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3 ± 3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota. The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.

Vaccinations in pediatric kidney transplant recipients.

PubMed

Fox, Thomas G; Nailescu, Corina

2018-04-18

Pediatric kidney transplant (KT) candidates should be fully immunized according to routine childhood schedules using age-appropriate guidelines. Unfortunately, vaccination rates in KT candidates remain suboptimal. With the exception of influenza vaccine, vaccination after transplantation should be delayed 3-6 months to maximize immunogenicity. While most vaccinations in the KT recipient are administered by primary care physicians, there are specific schedule alterations in the cases of influenza, hepatitis B, pneumococcal, and meningococcal vaccinations; consequently, these vaccines are usually administered by transplant physicians. This article will focus on those deviations from the normal vaccine schedule important in the care of pediatric KT recipients. The article will also review human papillomavirus vaccine due to its special importance in cancer prevention. Live vaccines are generally contraindicated in KT recipients. However, we present a brief review of live vaccines in organ transplant recipients, as there is evidence that certain live virus vaccines may be safe and effective in select groups. Lastly, we review vaccination of pediatric KT recipients prior to international travel.

Gut microbes contribute to variation in solid organ transplant outcomes in mice.

PubMed

McIntosh, Christine M; Chen, Luqiu; Shaiber, Alon; Eren, A Murat; Alegre, Maria-Luisa

2018-05-25

Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft

Corticosterone response to the plus-maze: high correlation with risk assessment in rats and mice.

PubMed

Rodgers, R J; Haller, J; Holmes, A; Halasz, J; Walton, T J; Brain, P F

Exposure to the elevated plus-maze induces behavioural and physiological effects in rodents consistent with fear/anxiety. Maze-naive animals display high levels of risk assessment towards the open arms, and explore these areas less extensively than other parts of the maze while, immediately following the test, pain latencies, skin conductance levels, and plasma corticosterone titres (CORT) are significantly elevated. Although previous research has suggested a link between the plasma CORT response and open-arm exploration, significant elevations in CORT have also been found with restricted exposure to the closed arms. The present study employed ethological measures in an attempt to further characterise the relationship between behavioural and CORT responses to this widely used animal model of anxiety. Our results confirm that, relative to home-cage controls, 5-min exposure to the plus-maze significantly increases plasma CORT levels in test-naive male Wistar rats and male Swiss-Webster mice. Furthermore, in both species, the CORT response was found to be highly correlated with measures of risk assessment (mice: rs = +0.87; rats: rs = +0.58), but not with measures of open-arm activity (entries, time), general locomotor activity, rearing, or head dipping. Findings are discussed in relation to the functional significance of risk assessment in potentially dangerous situations and the potential involvement of glucocorticoids in this process. All rights reserved.

Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis.

PubMed

Ismahil, Mohamed Ameen; Hamid, Tariq; Bansal, Shyam S; Patel, Bindiya; Kingery, Justin R; Prabhu, Sumanth D

2014-01-17

The role of mononuclear phagocytes in chronic heart failure (HF) is unknown. Our aim was to delineate monocyte, macrophage, and dendritic cell trafficking in HF and define the contribution of the spleen to cardiac remodeling. We evaluated C57Bl/6 mice with chronic HF 8 weeks after coronary ligation. As compared with sham-operated controls, HF mice exhibited: (1) increased proinflammatory CD11b+ F4/80+ CD206- macrophages and CD11b+ F4/80+ Gr-1(hi) monocytes in the heart and peripheral blood, respectively, and reduced CD11b+ F4/80+ Gr-1(hi) monocytes in the spleen; (2) significantly increased CD11c+ B220- classical dendritic cells and CD11c+ low)B220+ plasmacytoid dendritic cells in both the heart and spleen, and increased classic dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone marrow, respectively; (3) increased CD4+ helper and CD8+ cytotoxic T-cells in the spleen; and (4) profound splenic remodeling with abundant white pulp follicles, markedly increased size of the marginal zone and germinal centers, and increased expression of alarmins. Splenectomy in mice with established HF reversed pathological cardiac remodeling and inflammation. Splenocytes adoptively transferred from mice with HF, but not from sham-operated mice, homed to the heart and induced long-term left ventricular dilatation, dysfunction, and fibrosis in naive recipients. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice. Activation of mononuclear phagocytes is central to the progression of cardiac remodeling in HF, and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and dendritic cells) promote immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfer.

10 CFR 603.1325 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Recipient. 603.1325 Section 603.1325 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in... a for-profit recipient may be a firm or a segment of a firm (e.g., a division or other business unit). ...

Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

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

Onoe, K.; Good, R.A.; Yamamoto, K.

1986-06-01

Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, (BR----AKR), as well as syngeneic marrow cells, (AKR----AKR), showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice thatmore » had total or partial histoincompatibility at the H-2 determinants between donor and recipient, (B10----AKR), (B10.AQR----AKR), (B10.A(4R)----AKR), or (B10.A(5R)----AKR), were almost completely unresponsive in DTH and antibacterial immunity. However, when (B10----AKR) H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.« less

Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

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

Zhang, Yandong; Yu, Xinchun

The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors,more » the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.« less

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

CD4+ T Cells Mediate Aspergillosis Vaccine Protection.

PubMed

Diaz-Arevalo, Diana; Kalkum, Markus

2017-01-01

Adaptive effector CD4 + T cells play essential roles in the defense against fungal infections, especially against invasive aspergillosis (IA). Such protective CD4 + T cells can be generated through immunization with specialized antifungal vaccines, as has been demonstrated for pulmonary Aspergillus fumigatus infections in mouse experiments. Adaptive transfer of fungal antigen-specific CD4 + T cells conferred protection onto non-immunized naive mice, an experimental approach that could potentially become a future treatment option for immunosuppressed IA patients, focusing on the ultimate goal to improve their otherwise dim chances for survival. Here, we describe the different techniques to analyze CD4 + T cell immune responses after immunization with a recombinant fungal protein. We present three major methods that are used to analyze the role of CD4 + T cells in protection against A. fumigatus challenge. They include (1) transplantation of CD4 + T cells from vaccinated mice into immunosuppressed naive mice, observing increasing protection of the cell recipients, (2) depletion of CD4 + T cells from vaccinated mice, which abolishes vaccine protection, and (3) T cell proliferation studies following stimulation with overlapping synthetic peptides or an intact protein vaccine. The latter can be used to validate immunization status and to identify protective T cell epitopes in vaccine antigens. In the methods detailed here, we used versions of the well-studied Asp f3 protein expressed in a bacterial host, either as the intact full length protein or its N-terminally truncated version, comprised of residues 15-168. However, these methods are generally applicable and can well be adapted to study other protein-based subunit vaccines.

Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†.

PubMed

O'Donoghue, Michelle L; Ruff, Christian T; Giugliano, Robert P; Murphy, Sabina A; Grip, Laura T; Mercuri, Michele F; Rutman, Howard; Shi, Minggao; Kania, Grzegorz; Cermak, Ondrej; Braunwald, Eugene; Antman, Elliott M

2015-06-14

Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively). In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps

PubMed Central

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John

2018-01-01

Background: Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Objective: Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Methods: Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. Results: A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Conclusion: Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP. PMID:29336281

Absence of Activation-induced Cytidine Deaminase, a Regulator of Class Switch Recombination and Hypermutation in B Cells, Suppresses Aorta Allograft Vasculopathy in Mice.

PubMed

Nakanishi, Tomonori; Xu, Xiaoyan; Wynn, Carmen; Yamada, Toshiko; Pan, Fan; Erickson, Laurie; Teo, Haeman; Nakagawa, Terry; Masunaga, Taro; Abe, Jumpei; Akamatsu, Masahiko; Tamura, Kouichi; Jiang, Hongsi

2015-08-01

Antibody-mediated rejection is caused in part by increasing circulation/production of donor-specific antibody (DSA). Activation-induced cytidine deaminase (AID) is a key regulator of class switch recombination and somatic hypermutation of immunoglobulin in B cells, yet its role in antibody-mediated transplant rejection remains unclear. We show here that AID deficiency in mice enables suppression of allograft vasculopathy (AV) after aorta transplantation, a DSA-mediated process. Splenocytes from C57BL/6 J (B6) AID(−/−) mice were used for determining in vitro proliferation responses, alloreactivity, cell surface marker expression, and antibody production. BALB/c mouse aortas were transplanted into B6 AID(−/−) mice with or without FK506 treatment. Blood and aorta grafts were harvested on day 30 after transplantation and were subjected to DSA, histological, and immunohistological analyses. The AID(−/−) splenocytes were comparable to wild type splenocytes in proliferation responses, alloreactivity, and expression of cell surface markers in vitro. However, they completely failed to produce immunoglobulin G, although they were not impaired in immunoglobulin M production relative to controls. Furthermore, BALB/c aorta grafts from B6 AID(−/−) recipient mice on day 30 after transplantation showed reduced signs of AV compared to the grafts from B6 wild type recipient mice which had severe vascular intimal hyperplasia, interstitial fibrosis, and inflammation. Treatment with FK506 produced a synergistic effect in the grafts from AID(−/−) recipients with further reduction of intimal hyperplasia and fibrosis scores. The AID deficiency inhibits DSA-mediated AV after aorta transplantation in mice. We propose that AID could be a novel molecular target for controlling antibody-mediated rejection in organ transplantation.

An M2 Rather than a TH2 Response Contributes to Better Protection against Latency Reactivation following Ocular Infection of Naive Mice with a Recombinant Herpes Simplex Virus 1 Expressing Murine Interleukin-4.

PubMed

Lee, Dhong Hyun; Ghiasi, Homayon

2018-05-15

infected mice compared with their undepleted counterparts, with macrophage depletion increasing latency in the HSV-IL-4 group greater than 3,000-fold. Our results suggest that shifting the innate macrophage immune responses toward M2, rather than M1, responses in HSV-1 infection would improve protection against establishment of latency, reactivation, and eye disease. IMPORTANCE Ocular HSV-1 infections are among the most frequent serious viral eye infections in the United States and a major cause of virus-induced blindness. As establishment of a latent infection in the trigeminal ganglia results in recurrent infection and is associated with corneal scarring, prevention of latency reactivation is a major therapeutic goal. It is well established that absence of latency-associated transcripts (LATs) reduces latency reactivation. Here we demonstrate that recombinant HSV-1 expressing IL-4 (an inducer of T H 2/M2 responses) or IFN-γ (an inducer of T H 1/M1 responses) in place of LAT further reduced latency, with HSV-IL-4 showing the highest overall protective efficacy. In naive mice, this higher protective efficacy was mediated by innate rather than adaptive immune responses. Although both M1 and M2 macrophage responses were protective, shifting macrophages toward an M2 response through expression of IL-4 was more effective in curtailing ocular HSV-1 latency reactivation. Copyright © 2018 American Society for Microbiology.

Assistance received by employed caregivers and their care recipients: who helps care recipients when caregivers work full time?

PubMed

Scharlach, Andrew E; Gustavson, Kristen; Dal Santo, Teresa S

2007-12-01

This study examined the association among caregiver labor force participation, employees' caregiving activities, and the amount and quality of care received by care recipients. Telephone interviews were conducted with 478 adults who were employed full time and 705 nonemployed adults who provided care to a family member or friend aged 50 or older, identified through random sampling of California households. We assessed care recipient impairment and service problems; the amounts and types of assistance received from caregivers, family and friends, and paid providers; and caregiver utilization of support services. Care recipients of caregivers employed full time were less likely to receive large amounts of care from their caregivers, more likely to receive personal care from paid care providers, more likely to use community services, and more likely to experience service problems than were care recipients of nonemployed caregivers. Employed caregivers were more likely to use caregiver support services than were nonemployed caregivers. Accommodation to caregiver full-time employment involves selective supplementation by caregivers and their care recipients, reflecting increased reliance on formal support services as well as increased vulnerability to service problems and unmet care recipient needs. These findings suggest the need for greater attention to the well-being of disabled elders whose caregivers are employed full time.

14 CFR 1274.502 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... referred to such Federal, State or local authority as may have proper jurisdiction. ... AGREEMENTS WITH COMMERCIAL FIRMS Procurement Standards § 1274.502 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to NASA, regarding the settlement...

34 CFR 110.24 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As part... recipient employing the equivalent of 15 or more full-time employees to complete a written self-evaluation... Federal financial assistance from ED to assess the recipient's compliance with the Act. (b) Whenever an...

Shock anxiety among implantable cardioverter defibrillator recipients with recent tachyarrhythmia.

PubMed

Morken, Ingvild M; Isaksen, Kjetil; Karlsen, Bjørg; Norekvål, Tone M; Bru, Edvin; Larsen, Alf Inge

2012-11-01

Shock anxiety has been documented irrespective of shock exposure in implantable cardioverter defibrillator (ICD) recipients. The presence of tachyarrhythmia may lead to an anticipation of receiving a shock and thereby give rise to shock anxiety. The aims were to assess: (1) the level of shock anxiety in a sample of ICD recipients, (2) the relationship between such anxiety and shock exposure, and (3) the relationship between recent tachyarrhythmia and shock anxiety. ICD recipients (n = 167) completed the Florida Shock Anxiety Scale measure of shock anxiety. The recipients were divided into three groups: (1) Recipients with no documented tachyarrhythmia over the previous 12 months (n = 56), (2) recipients with documented tachyarrhythmia over the previous twelve months (n = 54), and (3) recipients with any history of shocks (n = 57). Of the recipients, 44% experienced some form of shock anxiety, whereas 15% reported general shock anxiety. Analyses of covariance revealed that recipients with recent tachyarrhythmia (F = 7.675 df = 9/100, P = 0.007) as well as recipients with a shock history (F = 9.976, df = 9/103, P = 0.002) reported higher levels of shock anxiety than recipients with no recent tachyarrhythmia. This study indicates that although a substantial proportion of the ICD recipients experienced some form of shock anxiety, only a relatively small proportion reported general shock anxiety. ICD recipients with recent tachyarrhythmia, in addition to recipients with shock history, appear to be at greater risk for development of shock anxiety. This implies that these recipients may profit from clinical-based strategies and interventions targeting shock anxiety. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

The Effect of Naive Ideas on Students' Reasoning about Electricity and Magnetism

ERIC Educational Resources Information Center

Leppavirta, Johanna

2012-01-01

Traditional multiple-choice concept inventories measure students' critical conceptual understanding and are designed to reveal students' naive or alternate ideas. The overall scores, however, give little information about the state of students' knowledge and the consistency of reasoning. This study investigates whether students have consistent…

CD72 ligation regulates defective naive newborn B cell responses.

PubMed

Howard, L M; Reen, D J

1997-02-01

The biological basis for reduced Ig production by naive newborn B cells compared to adult peripheral blood B cells is not fully understood. In a Con A + IL-2 T cell-dependent system using "competent" adult T cells, adult B cells produced large amounts of IgM, IgG, and IgA, while cord B cells were restricted to low levels of only IgM production. Cord B cell activation was also diminished. The contribution of specific B-T cell contact-mediated events to the diminished cord B cell response in this system, using mAbs to CD40, CD28, CD80, and CD72, were investigated, as well as regulation of B cell Ig production by cytokines. alphaCD72 ligation increased cord B cell activation and IgM production, but did not affect adult B cells. Blocking alphaCD40 mAb inhibited cord B cell Ig production completely, but only partly inhibited adult B cell Ig production even at high concentration, suggesting a greater sensitivity of cord B cells to disruption of the CD40-CD40L interaction. Addition of IL-10 did not increase cord B cell Ig production, while adult B cell Ig production was increased. However, combined addition of IL-10 and alphaCD72 significantly increased cord B cell Ig production over that in the presence of either alphaCD72 or IL-10 alone, but had no effect on adult B cells over that of IL-10 alone. These data suggest that the diminished T cell-dependent response of cord B cells is due to reduced or absent CD72 ligation. CD72 ligation plays an important role in the induction of primary responses by naive B cells. CD72 modulation of naive B cell sensitivity to IL-10 stimulation may have implications in the induction of class switch, which is deficient in newborn B cells. Since all T cells express CD5 constitutively, these data also suggest the existence of another ligand for CD72.

Cat odor exposure induces distinct changes in the exploratory behavior and Wfs1 gene expression in C57Bl/6 and 129Sv mice.

PubMed

Raud, Sirli; Sütt, Silva; Plaas, Mario; Luuk, Hendrik; Innos, Jürgen; Philips, Mari-Anne; Kõks, Sulev; Vasar, Eero

2007-10-16

129Sv and C57Bl/6 (Bl6) strains are two most widely used inbred mice strains for generation of transgenic animals. The present study confirms the existence of substantial differences in the behavior of these two mice strains. The exploratory behavior of Bl6 mice in a novel environment was significantly higher compared to 129Sv mice. The exposure of mice to cat odor-induced an anxiety-like state in Bl6, but not in 129Sv mice. The levels of Wfs1 gene expression did not differ in the prefrontal cortex, mesolimbic area and temporal lobe of experimentally naive Bl6 and 129Sv mice. However, after cat odor exposure the expression of Wfs1 gene was significantly lower in the mesolimbic area and temporal lobe of Bl6 mice compared to 129Sv strain. Dynamics of Wfs1 gene expression and exploratory behavior suggest that the down-regulation of Wfs1 gene in Bl6 mice might be related to the increased anxiety. Further studies are needed to test the robustness and possible causal relationship of this finding.

Children's Naive Theories of Intelligence Influence Their Metacognitive Judgments

ERIC Educational Resources Information Center

Miele, David B.; Son, Lisa K.; Metcalfe, Janet

2013-01-01

Recent studies have shown that the metacognitive judgments adults infer from their experiences of encoding effort vary in accordance with their naive theories of intelligence. To determine whether this finding extends to elementary schoolchildren, a study was conducted in which 27 third graders (M[subscript age] = 8.27) and 24 fifth graders…

22 CFR 226.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recipient responsibilities. 226.41 Section 226.41 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.41 Recipient...

40 CFR 35.134 - Eligible recipients.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Eligible recipients. 35.134 Section 35.134 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE... recipients. (a) Eligible agencies. All State agencies (including environmental, health, agriculture, and...

49 CFR 19.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... to be referred to such Federal, State or local authority as may have proper jurisdiction. ... Requirements Procurement Standards § 19.41 Recipient responsibilities. The standards contained in this section... recipient is the responsible authority, without recourse to the Federal awarding agency, regarding the...

45 CFR 1644.5 - Recipient policies and procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1644.5 Section 1644.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION DISCLOSURE OF CASE INFORMATION § 1644.5 Recipient policies and procedures. Each recipient shall adopt written...

45 CFR 1617.4 - Recipient policies and procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1617.4 Section 1617.4 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION CLASS ACTIONS § 1617.4 Recipient policies and procedures. Each recipient shall adopt written policies...

45 CFR 1639.6 - Recipient policies and procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1639.6 Section 1639.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION WELFARE REFORM § 1639.6 Recipient policies and procedures. Each recipient shall adopt written policies and...

Recent thymic emigrants and mature naive T cells exhibit differential DNA methylation at key cytokine loci.

PubMed

Berkley, Amy M; Hendricks, Deborah W; Simmons, Kalynn B; Fink, Pamela J

2013-06-15

Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4(+) RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.

Fuzzy Naive Bayesian model for medical diagnostic decision support.

PubMed

Wagholikar, Kavishwar B; Vijayraghavan, Sundararajan; Deshpande, Ashok W

2009-01-01

This work relates to the development of computational algorithms to provide decision support to physicians. The authors propose a Fuzzy Naive Bayesian (FNB) model for medical diagnosis, which extends the Fuzzy Bayesian approach proposed by Okuda. A physician's interview based method is described to define a orthogonal fuzzy symptom information system, required to apply the model. For the purpose of elaboration and elicitation of characteristics, the algorithm is applied to a simple simulated dataset, and compared with conventional Naive Bayes (NB) approach. As a preliminary evaluation of FNB in real world scenario, the comparison is repeated on a real fuzzy dataset of 81 patients diagnosed with infectious diseases. The case study on simulated dataset elucidates that FNB can be optimal over NB for diagnosing patients with imprecise-fuzzy information, on account of the following characteristics - 1) it can model the information that, values of some attributes are semantically closer than values of other attributes, and 2) it offers a mechanism to temper exaggerations in patient information. Although the algorithm requires precise training data, its utility for fuzzy training data is argued for. This is supported by the case study on infectious disease dataset, which indicates optimality of FNB over NB for the infectious disease domain. Further case studies on large datasets are required to establish utility of FNB.

Development of whole and demi-embryos of mice in culture and in vivo after supercooled storage.

PubMed

Fuku, E; Fiser, P S; Marcus, G J; Sasada, H; Downey, B R

1993-12-01

Demi-embryos (produced by destroying 1 or 2 blastomeres of 2- or 4-cell embryos, respectively) and intact mouse embryos were cultured to the blastocyst stage, stored at -5 degrees C for 48 h, then cultured for 24 h and transferred into pseudopregnant recipients. Supercooled storage did not impair the developmental potential of whole or demi-embryos in vitro, nor was there a difference between whole and demi-embryos with respect to growth in vitro. Similarly, there was no effect of supercooling on development of intact or demi embryos after transfer into pseudopregnant recipient mice, but fewer recipients of demi-embryos remained pregnant (P < 0.05). This was considered to be partly due to the lesser ability of demi-embryos to maintain luteal function and establish pregnancy.

22 CFR 518.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... statute are to be referred to such Federal, State or local authority as may have proper jurisdiction. ... Post-Award Requirements Procurement Standards § 518.41 Recipient responsibilities. The standards... contract(s). The recipient is the responsible authority, without recourse to the Federal awarding agency...

[Anti-mouse CD122 antibody promotes the hematopoietic repopulating capacity of cord blood CD34⁺ cells in NOD/SCID mice].

PubMed

Sheng, Men-Yao; Shi, Hui; Xing, Wen; Wang, Wen-Jun; Si, Xiao-Hui; Bai, Jie; Yuan, Wei-Ping; Zhou, Yuan; Yang, Feng-Chun

2014-12-01

The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.

TAM receptor knockout mice are susceptible to retinal autoimmune induction.

PubMed

Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

2011-06-16

TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

45 CFR 1610.8 - Program integrity of recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF NON-LSC FUNDS, TRANSFERS OF LSC FUNDS, PROGRAM INTEGRITY § 1610.8 Program integrity of recipient. (a) A recipient must have objective integrity and independence from any organization that engages in restricted activities. A recipient will be found to have objective integrity and independence from such an...

Myocarditis in mice and guinea pigs experimentally infected with a canine-origin Borrelia isolate from Florida.

PubMed

Breitschwerdt, E B; Geoly, F J; Meuten, D J; Levine, J F; Howard, P; Hegarty, B C; Stafford, L C

1996-04-01

To characterize the pathogenic potential of a unique Borrelia isolate obtained from a dog from Florida (FCB isolate). Prospective experimental infection. 32 preweanling Swiss Webster mice and 12 adult male Hartley guinea pigs were injected intraperitoneally with 10(5) spirochetes. Mice were used as controls and blood recipients, and at 3- to 4-day intervals, 1 control mouse and 2 infected mice were necropsied, tissues were cultured, and a recipient mouse was inoculated with blood. Guinea pigs were randomized to 4 groups and inoculated intradermally with 10(0), 10(2), 10(3), or 10(4) spirochetes. For 48 days, clinical, hematologic, serologic, and microbiologic tests were performed on them, after which they were necropsied. In mice, spirochetemia was detectable between postinoculation days (PID) 3 and 13, and seroreactivity to homologous antigen was detectable during PID 10 through 31. Compared with control mice, infected mouse spleens were 2 to 3 times larger. Histologic lesions included lymphoid hyperplasia, neutrophilic panniculitis, epicarditis, and myocarditis, with intralesional spirochetes detected from PID 3 through 6. During PID 10 through 31, nonsuppurative epicarditis developed. Signs of illness and hematologic abnormalities were not observed in guinea pigs, despite isolating spirochetes from blood during PID 7 to 27. When necropsied on PID 48, histologic lesions included lymphoid hyperplasia and lymphocytic plasmacytic epicarditis. The FCB isolate causes spirochetemia, lymphoid hyperplasia, dermatitis, and myocardial injury in Swiss Webster mice and can be transmitted by blood inoculation. In Hartley guinea pigs, the isolate causes spirochetemia, lymphoid hyperplasia, and epicarditis. Documentation of disease in mice, guinea pigs, and, presumably, dogs raises the level of concern that the FCB isolate might be pathogenic for man and other animal species.

Cardiac Troponins and Autoimmunity: their role in the pathogenesis of myocarditis and of heart failure

PubMed Central

Kaya, Ziya; Katus, Hugo A.; Rose, Noel R.

2010-01-01

Despite the widespread use of cardiac troponins as biomarkers for the diagnosis and quantitation of cardiac injury, the effect of troponin release and a possible autoimmune response to the troponins is unknown. Other investigators reported that programmed cell death – 1 (PD-1) – receptor deficient mice developed severe cardiomyopathy with autoantibodies to troponin I. We found that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. At later times, antibodies to cardiac myosin were detected in troponin – immunized mice. The severity of inflammation correlated with expression of chemokines RANTES, MIP-2, IP-10 and MCD-1 in the myocardium. Prior immunization with troponin I increased the severity of experimental infarctions, indicating that an autoimmune response to troponin I aggravates acute cardiac damage. Cardiac inflammation, fibrosis and functional impairment were transferred from immunized to naive recipients by CD4+ T cells, and the cytokine profile suggested both a Th2 and Th17 profile in A/J mice. Finally we identified an 18-mer of troponin I containing an immuno-dominant epitope. PMID:19446498

Nonmelanoma Skin Cancer in Nonwhite Organ Transplant Recipients.

PubMed

Pritchett, Ellen N; Doyle, Alden; Shaver, Christine M; Miller, Brett; Abdelmalek, Mark; Cusack, Carrie Ann; Malat, Gregory E; Chung, Christina Lee

2016-12-01

Organ transplant recipients have a higher incidence of skin cancer. This risk is magnified over time and with continued exposure to immunosuppression. Skin cancer in nonwhite patients is associated with greater morbidity and mortality owing to diagnosis at a more advanced stage, which suggests that nonwhite organ transplant recipients are at even higher risk. To describe demographic and clinical factors and the incidence of skin cancer in nonwhite organ transplant recipients. We performed a retrospective medical record review of patients who were organ transplant recipients (154 were white and 259 nonwhite [black, Asian, Hispanic, Pacific Islander]) seen from November 1, 2011, to April 18, 2016 at an academic referral center. Variables were analyzed and compared between racial groups, including sex, age, race/ethnicity, Fitzpatrick type, type and location of skin cancer, type of organ transplanted, time to diagnosis of skin cancer after transplantation, and history of condyloma acuminata and/or verruca vulgaris. Most of the 413 patients (62.7%) evaluated were nonwhite organ transplant recipients; 264 were men, and 149 were women. Their mean (SD) age was 60.09 (13.59) years. Nineteen skin cancers were identified in 15 patients (5.8%) representing 3 racial/ethnic groups: black (6 patients), Asian (5), and Hispanic (4). All squamous cell carcinomas in blacks were diagnosed in the in situ stage, located on sun-protected sites, and occurred in patients whose lesions tested positive for human papilloma virus (HPV) and/or who endorsed a history of condyloma acuminata or verruca vulgaris. Most skin cancers in Asians were located on sun-exposed areas and occurred in individuals who emigrated from equatorial locations. Nonwhite organ transplant recipients are at risk for developing skin cancer posttransplantation. Follow-up in a specialized transplant dermatology center and baseline total-body skin examination should be part of posttransplantation care in all organ

7 CFR 248.6 - Recipient eligibility.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 4 2014-01-01 2014-01-01 false Recipient eligibility. 248.6 Section 248.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.6...

7 CFR 248.6 - Recipient eligibility.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 4 2012-01-01 2012-01-01 false Recipient eligibility. 248.6 Section 248.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.6...

7 CFR 248.6 - Recipient eligibility.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 4 2011-01-01 2011-01-01 false Recipient eligibility. 248.6 Section 248.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.6...

7 CFR 248.6 - Recipient eligibility.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 4 2013-01-01 2013-01-01 false Recipient eligibility. 248.6 Section 248.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.6...

7 CFR 248.6 - Recipient eligibility.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Recipient eligibility. 248.6 Section 248.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.6...

41 CFR 105-74.660 - Recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Recipient. 105-74.660 Section 105-74.660 Public Contracts and Property Management Federal Property Management Regulations System...-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.660 Recipient...

15 CFR 14.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... violation of statute are to be referred to such Federal, State or local authority as may have proper... COMMERCIAL ORGANIZATIONS Post-Award Requirements Procurement Standards § 14.41 Recipient responsibilities... responsibilities arising under its contract(s). The recipient is the responsible authority, without recourse to the...

45 CFR 74.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... concerning violation of statute are to be referred to such Federal, State or local authority as may have... ORGANIZATIONS, AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Procurement Standards § 74.41 Recipient... responsibilities arising under its contract(s). The recipient is the responsible authority, without recourse to the...

28 CFR 70.41 - Recipient responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... violation of statute are to be referred to such Federal, State or local authority as may have proper... OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 70.41 Recipient... responsibilities arising under its contract(s). The recipient is the responsible authority, without recourse to the...

34 CFR 110.15 - Affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Affirmative action by recipients. 110.15 Section 110.15... ASSISTANCE Standards for Determining Age Discrimination § 110.15 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the...

45 CFR 91.16 - Affirmative action by recipient.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Affirmative action by recipient. 91.16 Section 91... for Determining Age Discrimination § 91.16 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of conditions...

43 CFR 17.315 - Affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Affirmative action by recipients. 17.315... Standards for Determining Age Discrimination § 17.315 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of...

43 CFR 17.315 - Affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Affirmative action by recipients. 17.315... Standards for Determining Age Discrimination § 17.315 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of...

34 CFR 110.15 - Affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Affirmative action by recipients. 110.15 Section 110.15... ASSISTANCE Standards for Determining Age Discrimination § 110.15 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the...

45 CFR 91.16 - Affirmative action by recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Affirmative action by recipient. 91.16 Section 91... for Determining Age Discrimination § 91.16 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of conditions...

Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

PubMed

Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

2018-01-01

In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

PubMed Central

Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

2012-01-01

Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

ANTIBODY FORMATION BY TRANSPLANTED BONE MARROW, SPLEEN, LYMPH NODE AND THYMUS CELLS IN IRRADIATED RECIPIENTS

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

Stoner, R.D.; Bond, V.P.

1963-01-14

Immunological competence of immunized mouse bone marrow, spleen, lymph node, and thymus cells was demonstrated when specific recall tetanus antitoxin responses were elicited after transfer of these cells to isologous irradiated mice or rats. Lesser amounts of antibody were obtained as the genetic strain distance was increased between the relation of donor and host in the parental to F/sub 1/ and in the homologous combination within the same species. It was not possible in the heterologous situation to elicit significant amounts of antibody from rat bone marrow and other lymphoid cells following their transplantation into irradiated mice. Minimal but notmore » significant antibody responses were elicited from cells obtained from immunized rat spleen and thymus tissue. In a few experiments, it was possible to elicit antibody formation from a buffy coat suspension of circulating white cells following their transfer to irradiated recipients. Isologous nonimmunized bone marrow did not stimulate or hasten recovery of the ability to eiicit secondary antibody responses in previously immunized irradiated mice. The capacity to elicit primary antibody responses to tetanus toxoid was depressed in parental-bone-marrow-protected F/sub 1/ mice when these chimeras exhibited varying degrees of secondary disease. The depression of primary antibody responses in irradiated F/sub 1/ mice given parental bone marrow provides evidence for a donor mediated immunological depression of antibody synthesis by host-lymphoid tissues. (auth)« less

EPA Grants Overview for Applicants and Recipients

EPA Pesticide Factsheets

The purpose of this training seminar is to ensure that EPA's nonprofit recipient community understands the assistance agreement regulations and EPA's nonprofit recipient community understands how to manage assistance agreements.

34 CFR 75.590 - Evaluation by the recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Evaluation by the recipient. 75.590 Section 75.590 Education Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS What Conditions Must Be Met by a Grantee? Evaluation § 75.590 Evaluation by the recipient. A recipient shall submit a performance...

7 CFR 3015.12 - Moneys advanced to recipients.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Moneys advanced to recipients. 3015.12 Section 3015... Moneys advanced to recipients. Any moneys advanced to recipients which are subject to the control or regulation of the United States or any of its officers, agents, or employees (public moneys as defined in...

7 CFR 3015.12 - Moneys advanced to recipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Moneys advanced to recipients. 3015.12 Section 3015... Moneys advanced to recipients. Any moneys advanced to recipients which are subject to the control or regulation of the United States or any of its officers, agents, or employees (public moneys as defined in...

7 CFR 3015.12 - Moneys advanced to recipients.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Moneys advanced to recipients. 3015.12 Section 3015... Moneys advanced to recipients. Any moneys advanced to recipients which are subject to the control or regulation of the United States or any of its officers, agents, or employees (public moneys as defined in...

7 CFR 3015.12 - Moneys advanced to recipients.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Moneys advanced to recipients. 3015.12 Section 3015... Moneys advanced to recipients. Any moneys advanced to recipients which are subject to the control or regulation of the United States or any of its officers, agents, or employees (public moneys as defined in...

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PubMed

Iglicki, Matias; Busch, Catharina; Zur, Dinah; Okada, Mali; Mariussi, Miriana; Chhablani, Jay Kumar; Cebeci, Zafer; Fraser-Bell, Samantha; Chaikitmongkol, Voraporn; Couturier, Aude; Giancipoli, Ermete; Lupidi, Marco; Rodríguez-Valdés, Patricio J; Rehak, Matus; Fung, Adrian Tien-Chin; Goldstein, Michaella; Loewenstein, Anat

2018-04-24

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10). Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

Systemic candidiasis in mice. II.--Main role of polymorphonuclear leukocytes in resistance to infection.

PubMed

Hurtrel, B; Lagrange, P H; Michel, J C

1980-01-01

Cyclophosphamide (CY) increased whereas the talc embedded in a calcium phosphate gel (TCP) decreased the susceptibility of mice to systemic candidiasis estimated by measuring mean survival time and "renal infectivity" 12 h after challenge. Transfers of plasma from CY- and TCP-treated mice did not modify cnadidiasis susceptibility of recipient mice. Granulopenia and granulocytosis induced respectively by CY and TCP were significantly correlated with susceptibility or resistance to candidiasis. Nevertheless, TCP produced significant reticuloendothelial stimulation which could be also correlated with TCP protection. Reticuloendothelial stimulation with associated granulopenia in TCP-CY-treated mice gave protection against Listeria monocytogenes challenge but not against Candida albicans. Thus, blood polymorphonuclear leukocytes seem to play the main role in natural resistance of mice to candidiasis. This was corroborated after injection of immunostimulants; a good correlation was found between C. albicans resistance and the induced granulocytosis.

Factor Affecting Transplant Outcomes in Diabetic Nude Mice Receiving Human, Porcine, and Non-Human Primate Islets: Analysis of 335 Transplantations

PubMed Central

Loganathan, Gopalakrishnan; Graham, Melanie L.; Radosevich, David M.; Soltani, Sajjad M.; Tiwari, Mukesh; Anazawa, Takayuki; papas, Klearchos K.; Sutherland, David E.R.; Hering, Bernhard J.; Balamurugan, A.N.

2013-01-01

Background In the absence of a reliable islet potency assay, nude mice transplant is the criterion standard to assess islet quality for clinical transplantation. There are factors other than islet quality that affect the transplant outcome. Methods Here, we analyzed the transplant outcomes in 335 nude mice (NM) receiving islets from human (n=103), porcine (n=205), and non-human primate (NHP) donors (n=27). The islets (750, 1000, and 2000 islet equivalents) were transplanted under the kidney capsule of streptozotocin (STZ) induced diabetic NM. Results The proportion of mice that achieved normoglycemia was significantly higher in the group implanted with 2000 IEQ of human, porcine, or NHP islets (75% normoglycemic) versus groups that were implanted with 750 IEQ (7% normoglycemic) and 1000 IEQ (30% normoglycemic). In this study, we observed that the purity of porcine islet preparations (P ≤ .001), islet pellet size in porcine preparations (P ≤ .01) and mice recipient body weight for human islets preparations (P =.013), was independently associated with successful transplant outcome. NHP islets of 1000 IEQ were sufficient to achieve normoglycemic condition (83%). An islet mass of 2000 IEQ, high islet purity, increased recipient body weight, and high islet pellet volume increased the likelihood of successful reversal of diabetes in transplanted mice. Also, higher insulin secretory status of islets at basal stimulus was associated with a reduced mouse cure rate. The cumulative incidence of graft failure was significantly greater in human islets (56.12%) compared with porcine islets 35.57% (P ≤ .001). Conclusion Factors affecting NM bioassay were identified (islet mass, islet purity, pellet size, in vitro insulin secretory capability and mouse recipient body weight) and should be considered when evaluating islet function. PMID:23677052

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

PubMed Central

Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

2016-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice

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

Marley, R.J.; Wehner, J.M.

Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of TH-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity tomore » 3-mercaptopropionic acid and differential enhancement of TH-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of TH-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.« less

Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea

PubMed Central

Yang, Jun; Zhao, Xiaofeng; Patel, Archana; Potru, Rachana; Azizi-Ghannad, Sadra; Dolinger, Michael; Mazurkiewicz, Joseph; Conti, David; Jones, David; Huang, Yunfei; Zhu, Xinjun

2016-01-01

Background & Aims The immunosuppressant rapamycin frequently causes non-infectious diarrhea in recipients of organ transplants. We investigated the mechanisms of this process. Methods We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsies from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of Mtor (mTORf/f:Villin-cre mice) or Atg7 (Atg7flox/flox; Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. Results Episodes of non-infectious diarrhea occurred in organ recipients following increases in serum levels of rapamycin. Expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). Intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amount of liquid stools; they also had reduced levels of total NHE3 and NHERF1, compared with control mice. We observed a significant reduction in Na+/H+ exchange activity in ileum tissues from these mice. Conclusions Rapamycin inhibition of mTOR reduces levels of NHE3 and Na+/H+ exchange activity in intestinal tissues of patients and rodents. This

Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea.

PubMed

Yang, Jun; Zhao, Xiaofeng; Patel, Archana; Potru, Rachana; Azizi-Ghannad, Sadra; Dolinger, Michael; Cao, James; Bartholomew, Catherine; Mazurkiewicz, Joseph; Conti, David; Jones, David; Huang, Yunfei; Zhu, Xinjun Cindy

2015-07-01

The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin (Mtor) (mTOR(f/f):Villin-cre mice) or Atg7 (Atg7(flox/flox); Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na(+)/H(+) exchange activity in ileum tissues from these mice. Rapamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tissues of patients and rodents

Mice with Reconstituted Human Immune System Components as a Tool to Study Immune Cell Interactions in EBV Infection.

PubMed

Heuts, Frank; Nagy, Noemi

2017-01-01

Recent developments in mouse models that harbor part of a human immune system have proved extremely valuable to study the in vivo immune response to human specific pathogens such as Epstein-Barr virus. Over the last decades, advances in immunodeficient mouse strains that can be used as recipients for human immune cells have greatly enhanced the use of these models. Here, we describe the generation of mice with reconstituted human immune system (HIS mice) using immunocompromised mice transplanted with human CD34 + hematopoietic stem cells. We will also describe how such mice, in which human immune cells are generated de novo, can be used to study EBV infection.

Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.

PubMed

Jaleco, Sara; Swainson, Louise; Dardalhon, Valérie; Burjanadze, Maryam; Kinet, Sandrina; Taylor, Naomi

2003-07-01

Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.

Evaluation of Th1/Th2-Related Immune Response against Recombinant Proteins of Brucella abortus Infection in Mice.

PubMed

Im, Young Bin; Park, Woo Bin; Jung, Myunghwan; Kim, Suk; Yoo, Han Sang

2016-06-28

Brucellosis is a zoonotic disease caused by Brucella, a genus of gram-negative bacteria. Cytokines have key roles in the activation of innate and acquired immunities. Despite several research attempts to reveal the immune responses, the mechanism of Brucella infection remains unclear. Therefore, immune responses were analyzed in mice immunized with nine recombinant proteins. Cytokine production profiles were analyzed in the RAW 264.7 cells and naive splenocytes after stimulation with three recombinant proteins, metal-dependent hydrolase (r0628), bacterioferritin (rBfr), and thiamine transporter substrate-binding protein (rTbpA). Immune responses were analyzed by ELISA and ELISpot assay after immunization with proteins in mice. The production levels of NO, TNF-α, and IL-6 were time-dependently increased after having been stimulated with proteins in the RAW 264.7 cells. In naive splenocytes, the production of IFN-γ and IL-2 was increased after stimulation with the proteins. It was concluded that two recombinant proteins, r0628 and rTbpA, showed strong immunogenicity that was induced with Th1-related cytokines IFN-γ, IL-2, and TNF-α more than Th2-related cytokines IL-6, IL-4, and IL-5 in vitro. Conversely, a humoral immune response was activated by increasing the number of antigen-secreting cells specifically. Furthermore, these could be candidate diagnosis antigens for better understanding of brucellosis.

Social participation and psychosocial outcomes of young adults with chronic physical conditions: Comparing recipients and non-recipients of disability benefits.

PubMed

Bal, Marjolijn I; Sattoe, Jane N T; Miedema, Harald S; van Staa, AnneLoes

2018-03-01

Little is known about any differences between young people with chronic physical conditions who do and do not apply for disability benefits in young adulthood for providing insights for future policy and rehabilitation care. We aimed to identify predictors during adolescence of receiving disability benefits in young adulthood and to compare recipients and non-recipients of benefits in social participation and psychosocial outcomes in young adulthood. Follow-up study of 18 to 25 year olds with various chronic conditions who at adolescent age completed a web-based survey (n=518; T0). The outcome was receiving disability benefits (yes or no). Associations with background characteristics, social participation, and impact of the chronic condition were explored with stepwise multivariate modelling, using T0 variables. Differences between recipients and non-recipients were explored using chi-square tests and t-tests. Receiving disability benefits in young adulthood was associated with greater extent of physical disability, receiving less special education, absenteeism at school/work, and low health-related quality of life during adolescence. In young adulthood, recipients of benefits reported higher perceived impact of the chronic condition on their school/work career and lower quality of life than non-recipients. Social participation varied across domains. This study provides important insights into the characteristics of a vulnerable subgroup of young people with chronic physical conditions. Disability benefit recipients experienced more impact of their chronic condition and reported a lower health-related quality of life over time than non-recipients. Rehabilitation professionals are encouraged to use patient-reported outcomes to address the lived experiences and screen the need for psychosocial support of this vulnerable subgroup of young people with chronic physical conditions. Copyright © 2018. Published by Elsevier Masson SAS.

25 CFR 170.163 - How are Indian LTAP recipients selected?

Code of Federal Regulations, 2011 CFR

2011-04-01

... applicants and recommends award recipients. FHWA selects and notifies award recipients consistent with... 25 Indians 1 2011-04-01 2011-04-01 false How are Indian LTAP recipients selected? 170.163 Section... Program § 170.163 How are Indian LTAP recipients selected? (a) FHWA announces Indian LTAP grant...

25 CFR 170.163 - How are Indian LTAP recipients selected?

Code of Federal Regulations, 2014 CFR

2014-04-01

... applicants and recommends award recipients. FHWA selects and notifies award recipients consistent with... 25 Indians 1 2014-04-01 2014-04-01 false How are Indian LTAP recipients selected? 170.163 Section... Program § 170.163 How are Indian LTAP recipients selected? (a) FHWA announces Indian LTAP grant...

25 CFR 170.163 - How are Indian LTAP recipients selected?

Code of Federal Regulations, 2013 CFR

2013-04-01

... applicants and recommends award recipients. FHWA selects and notifies award recipients consistent with... 25 Indians 1 2013-04-01 2013-04-01 false How are Indian LTAP recipients selected? 170.163 Section... Program § 170.163 How are Indian LTAP recipients selected? (a) FHWA announces Indian LTAP grant...

25 CFR 170.163 - How are Indian LTAP recipients selected?

Code of Federal Regulations, 2012 CFR

2012-04-01

... applicants and recommends award recipients. FHWA selects and notifies award recipients consistent with... 25 Indians 1 2012-04-01 2011-04-01 true How are Indian LTAP recipients selected? 170.163 Section... Program § 170.163 How are Indian LTAP recipients selected? (a) FHWA announces Indian LTAP grant...

25 CFR 170.163 - How are Indian LTAP recipients selected?

Code of Federal Regulations, 2010 CFR

2010-04-01

... applicants and recommends award recipients. FHWA selects and notifies award recipients consistent with... 25 Indians 1 2010-04-01 2010-04-01 false How are Indian LTAP recipients selected? 170.163 Section... Program § 170.163 How are Indian LTAP recipients selected? (a) FHWA announces Indian LTAP grant...

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens

PubMed Central

Yi, Huanfa; Yu, Xiaofei; Guo, Chunqing; Manjili, Masoud H.; Repasky, Elizabeth A.; Wang, Xiang-Yang

2011-01-01

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naive female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer. PMID:21088965

Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.

PubMed

von Meyenn, Ferdinand; Iurlaro, Mario; Habibi, Ehsan; Liu, Ning Qing; Salehzadeh-Yazdi, Ali; Santos, Fátima; Petrini, Edoardo; Milagre, Inês; Yu, Miao; Xie, Zhenqing; Kroeze, Leonie I; Nesterova, Tatyana B; Jansen, Joop H; Xie, Hehuang; He, Chuan; Reik, Wolf; Stunnenberg, Hendrik G

2016-06-16

Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

10 CFR 4.338 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Remedial and affirmative action by recipients. 4.338... and affirmative action by recipients. (a) Where NRC finds a recipient has discriminated on the basis... discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted in...

10 CFR 4.338 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Remedial and affirmative action by recipients. 4.338... and affirmative action by recipients. (a) Where NRC finds a recipient has discriminated on the basis... discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted in...

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

PubMed

Papageorgiou, C; Kontaxakis, V P; Havaki-Kontaxaki, B J; Stamouli, S; Vasios, C; Asvestas, P; Matsopoulos, G K; Kontopantelis, E; Rabavilas, A; Uzunoglu, N; Christodoulou, G N

2001-09-17

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

Cancer in the Transplant Recipient

PubMed Central

Chapman, Jeremy R.; Webster, Angela C.; Wong, Germaine

2013-01-01

Malignancy has become one of the three major causes of death after transplantation in the past decade and is thus increasingly important in all organ transplant programs. Death from cardiovascular disease and infection are both decreasing in frequency from a combination of screening, prophylaxis, aggressive risk factor management, and interventional therapies. Cancer, on the other hand, is poorly and expensively screened for; risk factors are mostly elusive and/or hard to impact on except for the use of immunosuppression itself; and finally therapeutic approaches to the transplant recipient with cancer are often nihilistic. This article provides a review of each of the issues as they come to affect transplantation: cancer before wait-listing, cancer transmission from the donor, cancer after transplantation, outcomes of transplant recipients after a diagnosis of cancer, and the role of screening and therapy in reducing the impact of cancer in transplant recipients. PMID:23818517

Use of the mice passive protection test to evaluate the humoral response in goats vaccinated with Sterne 34F2 live spore vaccine.

PubMed

Phaswana, P H; Ndumnego, O C; Koehler, S M; Beyer, W; Crafford, J E; van Heerden, H

2017-09-07

The Sterne live spore vaccine (34F2) is the most widely used veterinary vaccine against anthrax in animals. Antibody responses to several antigens of Bacillus anthracis have been described with a large focus on those against protective antigen (PA). The focus of this study was to evaluate the protective humoral immune response induced by the live spore anthrax vaccine in goats. Boer goats vaccinated twice (week 0 and week 12) with the Sterne live spore vaccine and naive goats were used to monitor the anti-PA and toxin neutralizing antibodies at week 4 and week 17 (after the second vaccine dose) post vaccination. A/J mice were passively immunized with different dilutions of sera from immune and naive goats and then challenged with spores of B. anthracis strain 34F2 to determine the protective capacity of the goat sera. The goat anti-PA ELISA titres indicated significant sero-conversion at week 17 after the second doses of vaccine (p = 0.009). Mice receiving undiluted sera from goats given two doses of vaccine (twice immunized) showed the highest protection (86%) with only 20% of mice receiving 1:1000 diluted sera surviving lethal challenge. The in vitro toxin neutralization assay (TNA) titres correlated to protection of passively immunized A/J mice against lethal infection with the vaccine strain Sterne 34F2 spores using immune goat sera up to a 1:10 dilution (r s  ≥ 0.522, p = 0.046). This study suggests that the passive mouse protection model could be potentially used to evaluate the protective immune response in livestock animals vaccinated with the current live vaccine and new vaccines.

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

PubMed

Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

2016-02-26

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Recipients Affect Prosocial and Altruistic Choices in Jackdaws, Corvus monedula

PubMed Central

Schwab, Christine; Swoboda, Ruth; Kotrschal, Kurt; Bugnyar, Thomas

2012-01-01

Other-regarding preferences are a critical feature of human cooperation but to what extent non-human animals exhibit these preferences is a matter of intense discussion. We tested whether jackdaws show prosocial behaviour (providing benefits to others at no cost to themselves) and altruism (providing benefits to others while incurring costs) with both sibling and non-sibling recipients. In the prosocial condition, a box was baited on both the actor's and the recipient's side (1/1 option), whereas another box provided food only for the actor (1/0 option). In the altruistic condition, the boxes contained food for either the actor (1/0 option) or the recipient (0/1 option). The proportion of selfish (1/0 option) and cooperative (1/1 and 0/1 option, respectively) actors' choices was significantly affected by the recipients' behaviour. If recipients approached the boxes first and positioned themselves next to the box baited on their side, trying to access the food reward (recipient-first trials), actors were significantly more cooperative than when the actors approached the boxes first and made their choice prior to the recipients' arrival (actor-first trials). Further, in recipient-first trials actors were more cooperative towards recipients of the opposite sex, an effect that was even more pronounced in the altruistic condition. Hence, at no cost to the actors, all recipients could significantly influence the actors' behaviour, whereas at high costs this could be achieved even more so by recipients of different sex. Local/stimulus enhancement is discussed as the most likely cognitive mechanism to account for these effects. PMID:22511972

Recipients affect prosocial and altruistic choices in jackdaws, Corvus monedula.

PubMed

Schwab, Christine; Swoboda, Ruth; Kotrschal, Kurt; Bugnyar, Thomas

2012-01-01

Other-regarding preferences are a critical feature of human cooperation but to what extent non-human animals exhibit these preferences is a matter of intense discussion. We tested whether jackdaws show prosocial behaviour (providing benefits to others at no cost to themselves) and altruism (providing benefits to others while incurring costs) with both sibling and non-sibling recipients. In the prosocial condition, a box was baited on both the actor's and the recipient's side (1/1 option), whereas another box provided food only for the actor (1/0 option). In the altruistic condition, the boxes contained food for either the actor (1/0 option) or the recipient (0/1 option). The proportion of selfish (1/0 option) and cooperative (1/1 and 0/1 option, respectively) actors' choices was significantly affected by the recipients' behaviour. If recipients approached the boxes first and positioned themselves next to the box baited on their side, trying to access the food reward (recipient-first trials), actors were significantly more cooperative than when the actors approached the boxes first and made their choice prior to the recipients' arrival (actor-first trials). Further, in recipient-first trials actors were more cooperative towards recipients of the opposite sex, an effect that was even more pronounced in the altruistic condition. Hence, at no cost to the actors, all recipients could significantly influence the actors' behaviour, whereas at high costs this could be achieved even more so by recipients of different sex. Local/stimulus enhancement is discussed as the most likely cognitive mechanism to account for these effects.

Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

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

Managlia, Elizabeth Z.; Landay, Alan; Al-Harthi, Lena

2006-07-05

Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF{kappa}B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated inductionmore » of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN{gamma}, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator.« less

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

PubMed Central

Marsh, Angie K.; Huibner, Sanja; Shahabi, Kamnoosh; Liu, Cindy; Contente, Tania; Nagelkerke, Nico J. D.; Kovacs, Colin; Benko, Erika; Price, Lance; MacDonald, Kelly S.; Kaul, Rupert

2017-01-01

Abstract Background. This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. Methods. Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. Results. Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels. Conclusions. Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway. PMID:28534034

Influenza vaccine strategies for solid organ transplant recipients.

PubMed

Hirzel, Cédric; Kumar, Deepali

2018-05-15

The aim of this study was to highlight recent evidence on important aspects of influenza vaccination in solid organ transplant recipients. Influenza vaccine is the most evaluated vaccine in transplant recipients. The immunogenicity of the vaccine is suboptimal after transplantation. Newer formulations such as inactivated unadjuvanted high-dose influenza vaccine and the administration of a booster dose within the same season have shown to increase response rates. Intradermal vaccination and adjuvanted vaccines did not show clear benefit over standard influenza vaccines. Recent studies in transplant recipients do not suggest a higher risk for allograft rejection, neither after vaccination with a standard influenza vaccine nor after the administration of nonstandard formulation (high-dose, adjuvanted vaccines), routes (intradermally) or a booster dose. Nevertheless, influenza vaccine coverage in transplant recipients is still unsatisfactory low, potentially due to misinterpretation of risks and benefits. Annual influenza vaccination is well tolerated and is an important part of long-term care of solid organ transplant recipients.

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma.

PubMed

Sasse, Stephanie; Rothe, Achim; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Kreher, Stephan; Jäger, Ulrich; Bangard, Christopher; Kuhnert, Georg; Böll, Boris; von Tresckow, Bastian; Engert, Andreas

2013-10-01

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT (n = 4) or allogeneic SCT (n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL.

Otitis Media and Nasopharyngeal Colonization in ccl3-/- Mice.

PubMed

Deniffel, Dominik; Nuyen, Brian; Pak, Kwang; Suzukawa, Keigo; Hung, Jun; Kurabi, Arwa; Wasserman, Stephen I; Ryan, Allen F

2017-11-01

We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of ccl3 -/- mice to nontypeable Haemophilus influenzae (NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced in ccl3 -/- and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by an in vitro assay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline. ccl3 -/- deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads in ccl3 -/- mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease. Copyright © 2017 American Society for Microbiology.

34 CFR 110.24 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As part...

34 CFR 110.24 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As part...

34 CFR 110.24 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As part...

34 CFR 110.24 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As part...

42 CFR 441.102 - Plan of care for institutionalized recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... include— (1) An initial review of the recipient's medical, psychiatric, and social needs— (i) Within 90... recipient. (2) Periodic review of the recipient's medical, psychiatric, and social needs; (3) A...

40 CFR 35.6285 - Recipient payment of response costs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... payment of response costs. The recipient may pay for its share of response costs using cash, services... costs in the form of cash. (b) Services. The recipient may provide equipment and services to satisfy its... CFR part 300). (d) Excess cash cost share contributions/overmatch. The recipient may direct EPA to...

34 CFR 303.2 - Eligible recipients of an award.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Eligible recipients of an award. 303.2 Section 303.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION... recipients of an award. Eligible recipients include the 50 States, the Commonwealth of Puerto Rico, the...

34 CFR 303.2 - Eligible recipients of an award.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Eligible recipients of an award. 303.2 Section 303.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION... recipients of an award. Eligible recipients include the 50 States, the Commonwealth of Puerto Rico, the...

Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China.

PubMed

Guo, Jinlei; Yan, Yong; Zhang, Jiafeng; Ji, Jimei; Ge, Zhijian; Ge, Rui; Zhang, Xiaofei; Wang, Henghui; Chen, Zhongwen; Luo, Jianyong

2017-03-14

The aim of this study was to characterize HIV-1 genotypes and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China. The HIV-1 partial polymerase (pol) genes in 93 of the 99 plasma samples were successfully amplified and analyzed. Phylogenetic analysis revealed the existence of five HIV-1 genotypes, of which the most prevalent genotype was CRF01_AE (38.7%), followed by CRF07_BC (34.4%), CRF08_BC (16.1%), subtype B/B' (5.4%), and CRF55_01B (2.1%). Besides, three types of unique recombination forms (URFs) were also observed, including C/F2/A1, CRF01_AE/B, and CRF08_BC/CRF07_BC. Among 93 amplicons, 46.2% had drug resistance-associated mutations, including 23.7% for protease inhibitors (PIs) mutations, 1.1% for nucleoside reverse transcriptase inhibitors (NRTIs) mutations, and 20.4% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations. Six (6.5%) out of 93 treatment-naive subjects were identified to be resistant to one or more NNRTIs, while resistance to NRTIs or PIs was not observed. Our study showed the genetic diversity of HIV-1 strains circulating in Jiaxing and a relative high proportion of antiretroviral resistance mutations among treatment-naive patients, indicating a serious challenge for HIV prevention and treatment program.

7 CFR 3015.91 - Monitoring by recipients.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-supported activities to assure that performance goals are being achieved. Recipient monitoring shall cover... 7 Agriculture 15 2013-01-01 2013-01-01 false Monitoring by recipients. 3015.91 Section 3015.91..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Monitoring and Reporting Program Performance...

7 CFR 3015.91 - Monitoring by recipients.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-supported activities to assure that performance goals are being achieved. Recipient monitoring shall cover... 7 Agriculture 15 2014-01-01 2014-01-01 false Monitoring by recipients. 3015.91 Section 3015.91..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Monitoring and Reporting Program Performance...

7 CFR 3015.91 - Monitoring by recipients.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-supported activities to assure that performance goals are being achieved. Recipient monitoring shall cover... 7 Agriculture 15 2012-01-01 2012-01-01 false Monitoring by recipients. 3015.91 Section 3015.91..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Monitoring and Reporting Program Performance...

7 CFR 3015.91 - Monitoring by recipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-supported activities to assure that performance goals are being achieved. Recipient monitoring shall cover... 7 Agriculture 15 2011-01-01 2011-01-01 false Monitoring by recipients. 3015.91 Section 3015.91..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Monitoring and Reporting Program Performance...

40 CFR 35.6790 - High risk recipients.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false High risk recipients. 35.6790 Section 35.6790 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients. If...

A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T Cells during Early T-Cell Receptor Activation*

PubMed Central

Graessel, Anke; Hauck, Stefanie M.; von Toerne, Christine; Kloppmann, Edda; Goldberg, Tatyana; Koppensteiner, Herwig; Schindler, Michael; Knapp, Bettina; Krause, Linda; Dietz, Katharina; Schmidt-Weber, Carsten B.; Suttner, Kathrin

2015-01-01

Naive CD4+ T cells are the common precursors of multiple effector and memory T-cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell-like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4+ T cells and their changes during the early phase of T-cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed oxime ligation technology was applied with subsequent quantitative liquid chromatography-tandem MS to generate a data set describing the surface proteome of primary human naive CD4+ T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins. To independently confirm the proteomic data set and to analyze the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous data set, resulting in 229 surface proteins, which were expressed on naive unstimulated and activated CD4+ T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation, and predicted subcellular localization, and correlated the proteomics result with this transcriptional data set. This extensive surface atlas provides an overall naive CD4+ T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T-cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments. PMID:25991687

Melanoma risk and survival among organ transplant recipients

PubMed Central

Robbins, Hilary A.; Clarke, Christina A.; Arron, Sarah T.; Tatalovich, Zaria; Kahn, Amy R.; Hernandez, Brenda Y.; Paddock, Lisa; Yanik, Elizabeth L.; Lynch, Charles F.; Kasiske, Bertram L.; Snyder, Jon; Engels, Eric A.

2015-01-01

Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked U.S. transplant-cancer registry data (1987–2010). We used standardized incidence ratios (SIRs) to compare incidence to the general population, and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (N=182) and non-recipients (N=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (N=519) was elevated (SIR=2.20, 95%CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95%CI 3.27–5.09). Risk of localized tumors was stable over time after transplantation, but higher with azathioprine maintenance therapy (IRR=1.35, 95%CI 1.03–1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95%CI 1.02–2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (HR 2.98, 95%CI 2.26–3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with ultraviolet radiation, while T-cell depleting induction therapies may promote late stage tumors. Our findings support sun safety practices and skin screening for transplant recipients. PMID:26270022

Predicting the ideal serum creatinine of kidney transplant recipients by a simple formula based on the balance between metabolic demands of recipients and renal mass supply from donors.

PubMed

Oh, C K; Lee, B M; Kim, H; Kim, S I; Kim, Y S

2008-09-01

Serum creatinine (Scr) is the most frequently used test to estimate graft function after kidney transplantation. Our previous study demonstrated that the independent predictors of recipient posttransplantation Scr included the ratio of graft weight to recipient body weight, the ratio of graft weight to recipient body surface area (BSA), and the ratio of graft weight to recipient body mass index (BMI). A prospective analysis about the impact of the balance between metabolic demands and renal supply on posttransplantation Scr of recipients was previously reported. We plotted the scatter graph using the X-axis as the independent predictors of Scr by linear regression and the Y-axis as the recipient Scr. To generate the predictive formula of Scr, we calculated a fit of the line of plotted cases using a linear regression method with 2 regression lines for prediction of the upper and lower 95% confidence intervals. Each line was converted into a predictive formula: Scr = -0.0033* (Graft weight(g)/Recipient BSA(m2))+1.75. Under 95% confidence, the Scr ranges from -0.0033* (Graft weight(g)/Recipient BSA(m2))+1.07 to -0.0033* (Graft weight(g)/Recipient BSA (m2))+2.44. Scr = -0.1049* (Graft weight(g)/Recipient body weight(kg))+1.72, which ranges from -0.1049* (Graft weight(g)/Recipient body weight(kg))+1.06 to -0.1049* (Graft weight(g)/Recipient body weight(kg))+2.37. Scr = -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+1.56, which ranges from -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+0.75 to -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+2.26. Prediction of posttransplantation Scr may be achieved by measuring graft weight as well as recipient weight and height. When recipient Scr is significantly higher than that predicted by the formula, a clinician should suspect an underlying graft injury.

29 CFR 35.26 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

29 CFR 35.26 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

29 CFR 35.26 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

29 CFR 35.26 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

29 CFR 35.26 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 1 2014-07-01 2013-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

The Relationship Between Mental Representations of Welfare Recipients and Attitudes Toward Welfare.

PubMed

Brown-Iannuzzi, Jazmin L; Dotsch, Ron; Cooley, Erin; Payne, B Keith

2017-01-01

Scholars have argued that opposition to welfare is, in part, driven by stereotypes of African Americans. This argument assumes that when individuals think about welfare, they spontaneously think about Black recipients. We investigated people's mental representations of welfare recipients. In Studies 1 and 2, we used a perceptual task to visually estimate participants' mental representations of welfare recipients. Compared with the average non-welfare-recipient image, the average welfare-recipient image was perceived (by a separate sample) as more African American and more representative of stereotypes associated with welfare recipients and African Americans. In Study 3, participants were asked to determine whether they supported giving welfare benefits to the people pictured in the average welfare-recipient and non-welfare-recipient images generated in Study 2. Participants were less supportive of giving welfare benefits to the person shown in the welfare-recipient image than to the person shown in the non-welfare-recipient image. The results suggest that mental images of welfare recipients may bias attitudes toward welfare policies.

Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells.

PubMed

Quinn, Kylie M; Fox, Annette; Harland, Kim L; Russ, Brendan E; Li, Jasmine; Nguyen, Thi H O; Loh, Liyen; Olshanksy, Moshe; Naeem, Haroon; Tsyganov, Kirill; Wiede, Florian; Webster, Rosela; Blyth, Chantelle; Sng, Xavier Y X; Tiganis, Tony; Powell, David; Doherty, Peter C; Turner, Stephen J; Kedzierska, Katherine; La Gruta, Nicole L

2018-06-19

Age-associated decreases in primary CD8 + T cell responses occur, in part, due to direct effects on naive CD8 + T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (T VM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that T VM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (T N cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged T VM cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Aspergillus spondylodiscitis in solid organ transplant recipients.

PubMed

Li, X-F; Liu, Z-D; Xia, Q; Dai, L-Y

2010-12-01

Transplantation practices have had a significant effect on the epidemiology of invasive Aspergillosis. Aspergillus spondylodiscitis is rare in transplant recipients. The optimal treatment has yet to be defined because of the rarity of such cases. This article reviews the available literature on Aspergillus spondylodiscitis in solid organ transplant recipients and provides recommendations on its management. We identified 15 cases of Aspergillus spondylodiscitis in transplant recipients. Most patients were heart transplant recipients. Back pain was the mode of presentation in all patients. Most cases were afebrile. The dominant location was the lumbar spine. Aspergillus fumigatus was responsible for 84.62% of cases and A flavus for 15.38%. The overall recovery rate was 66.67%. Delay in diagnosis remained a major impediment to the successful treatment of spinal aspergillosis. Treatment included antifungal therapy alone or combined with surgery. Initial therapy with voriconazole could lead to better curative effects. Combined medical and operative interventions are recommended for treatment. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed

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

2001-12-01

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

A majority of mice show long-term expression of a human. beta. -globin gene after retrovirus transfer into hematopoietic stem cells

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

Bender, M.A.; Gelinas, R.E.; Miller

1989-04-01

Murine bone marrow was infected with a high-titer retrovirus vector containing the human {beta}-globin and neomycin phosphotransferase genes. Anemic W/W/sup v/ mice were transplanted with infected marrow which in some cases had been exposed to the selective agent G418. Human {beta}-globin expression was monitored in transplanted animals by using a monoclonal antibody specific for human {beta}-globin polypeptide, and hematopoietic reconstitution was monitored by using donor and recipient mice which differed in hemoglobin type. In some experiments all transplanted mice expressed the human {beta}-globin polypeptide for over 4 months, and up to 50% of peripheral erythrocytes contained detectable levels of polypeptide.more » DNA analysis of transplanted animals revealed that virtually every myeloid cell contained a provirus. Integration site analysis and reconstitution of secondary marrow recipients suggested that every mouse was reconstituted with at least one infected stem cell which had extensive repopulation capability. The ability to consistently transfer an active {beta}-globin gene into mouse hematopoietic cells improves the feasibility of using these techniques for somatic cell gene therapy in humans.« less

Inactivated coxsackievirus A10 experimental vaccines protect mice against lethal viral challenge.

PubMed

Shen, Chaoyun; Liu, Qingwei; Zhou, Yu; Ku, Zhiqiang; Wang, Lili; Lan, Ke; Ye, Xiaohua; Huang, Zhong

2016-09-22

Coxsackievirus A10 (CVA10) has become one of the major causative agents of hand, foot and mouth disease (HFMD). It is now recognized that CVA10 should be targeted for vaccine development. We report here that β-propiolactone inactivated whole-virus based CVA10 vaccines can elicit protective immunity in mice. We prepared two inactivated CVA10 experimental vaccines derived from the prototype strain CVA10/Kowalik and from a clinical isolate CVA10/S0148b, respectively. Immunization with the experimental vaccines elicited CVA10-specific serum antibodies in mice. The antisera from vaccinated mice could potently neutralize in vitro infection with either homologous or heterologous CVA10 strains. Importantly, passive transfer of the anti-CVA10 sera protected recipient mice against CVA10/Kowalik or CVA10/S0148b infections. Moreover, active immunization with the inactivated vaccines also conferred protection against homologous and heterologous infections in mice. Collectively, our results demonstrate the proof-of-concept for inactivated whole-virus based CVA10 vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Job Performance and Retention among Welfare Recipients.

ERIC Educational Resources Information Center

Holzer, Harry J.; Stoll, Michael A.; Wissoker, Douglas

Data from interviews with 750 employers in Chicago, Cleveland, Milwaukee, and Los Angeles were used to analyze the job performance and retention rates of recently hired welfare recipients. The 20-minute interviews focused on employers' subjective ratings of recently hired welfare recipients' job performance and whether employers experienced the…

Exploring the Autonomous Economic World of Children: A Mixed Methods Study of Kids' Naive Economic Theories Incorporating Ethnographic and Behavioral Economics Methodologies

ERIC Educational Resources Information Center

Jennings, Amanda Brooke

2017-01-01

Children construct meaning from their economic experiences in the form of naive theories and use these theories to explain the relationships between their actions and the outcomes. Inevitably, due to their lack of economic literacy, these theories will be incomplete. Through curriculum design that acknowledges and addresses these naive theories,…

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

Training NIH K award recipients: the role of the mentor.

PubMed

Ripley, Elizabeth; Markowitz, Monika; Nichols-Casebolt, Ann; Williams, Larry; Macrina, Francis

2012-10-01

Mentors play important roles in training new investigators. This study was designed to determine characteristics of NIH mentored K award recipients and their mentors, their interpersonal interactions, and the factors, which influence satisfaction within this relationship. A survey of 3027 NIH mentored K recipients and 1384 mentors was conducted in 2009. Nine hundred twenty-nine (30.7%) of the K recipients and 448 (32.4%) mentors completed the survey. The gender of K respondents was evenly divided while the mentors were 72.1% male. The overall rating of their mentors was positive. Ideally, both thought the mentor should be important in research training; however, in actual practice, both rated the importance as lower. A total of 88.2% of recipients were satisfied with their relationship. Although the number of black K recipients was low, this group was more likely to be dissatisfied with the mentor relationship (6/29 or 20.7%) than their white counterparts. The frequency of meeting or communicating was correlated with K recipient satisfaction. Overall K recipients are satisfied with their mentor relationships. Although the number of black K recipient respondents was small, the higher level of mentor dissatisfaction should be further evaluated. Qualities of mentors, including the frequency of interactions and accessibility, can influence satisfaction. © 2012 Wiley Periodicals, Inc.

Achieving ventricular rate control using metoprolol in β-blocker-naive patients vs patients on chronic β-blocker therapy.

PubMed

Kuang, Patricia; Mah, Nathan D; Barton, Cassie A; Miura, Andrea J; Tanas, Laura R; Ran, Ran

2016-03-01

The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic β-blocker therapy compared to patients considered β-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate. A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded. A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic β-blocker therapy. Patients considered to be β-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic β-blocker therapy (56.1% vs 42.4%; P=.03). β-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic β-blocker therapy (1.79 vs 2.64 days; P<.01). Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered β-blocker naive compared to patients receiving chronic β-blocker therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

21 CFR 99.105 - Recipients of information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Recipients of information. 99.105 Section 99.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... Disseminated § 99.105 Recipients of information. A manufacturer disseminating information on a new use under...

Self-management and self-efficacy status in liver recipients.

PubMed

Xing, Lei; Chen, Qin-Yun; Li, Jia-Ning; Hu, Zhi-Qiu; Zhang, Ye; Tao, Ran

2015-06-01

Liver transplantation (LT) is a viable treatment for patients with end-stage chronic liver diseases. The main aim of LT is to prolong life and improve life quality. However, although survival after LT continues to improve, some aspects of recipient's health-related quality of life such as self-management and self-efficacy have been largely ignored. A total of 124 LT recipients were included in this study. Questionnaires for general health status information and a "Self-Management Questionnaire for Liver Transplantation Recipients" modified from the Chinese version of "Chronic Disease Self-Management Program Questionnaire Code Book" were used in the survey. Data were collected by self-administered questionnaires. The overall status of self-management in LT recipients was not optimistic. The major variables affecting the self-management of LT recipients were marital status, educational level and employment. The overall status of self-efficacy in LT recipients was around the medium-level. Postoperative time and self-assessment of overall health status were found as the factors impacting on self-efficacy. The self-management behavior of LT recipients needs to be improved. The health care professionals need to offer targeted health education to individual patients, help them to establish healthy lifestyle, enhance physical activity and improve self-efficacy. The development of the multilevel and multifaceted social support system will greatly facilitate the self-management in LT patients.

Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

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

Li Hongwei; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908; Li Jinzhong

PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10{sup 9} PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of themore » luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.« less

Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

ERIC Educational Resources Information Center

Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

2010-01-01

Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

Impaired protection against Trichinella spiralis in mice with high levels of IgE.

PubMed

Watanabe, Naohiro

2014-04-01

Helminth infection induces production of a large amount of immunoglobulin E (IgE) to nonhelminth antigens. Although such "irrelevant" IgE is a major proportion of total IgE in the host, its biological significance remains unclear. Therefore, I examined protective activity against Trichinella spiralis in mice with high levels of IgE by repeated injections of anti-dansyl IgE monoclonal antibody or Nippostrongylus brasiliensis infection. Injected anti-dansyl IgE occupied IgE receptors on mast cells in naive mice. Protective activity against T. spiralis, determined with number of muscle larvae 5weeks after infection, was impaired in mice treated with anti-dansyl IgE. The impaired protection was found in mice treated with anti-dansy IgE 7 and 14days after infection, but not 21 and 28days after infection, indicating that IgE-dependent protection operates at an early stage after infection. In the next experiments, mice were infected with N. brasiliensis 4weeks before T. spiralis infection to obtain high levels of IgE. The protective activity against T. spiralis was decreased by N. brasiliensis infection. On the other hand, protection against T. spiralis was comparable in IgE-deficient SJA/9 mice and in anti-IgE-treated BALB/c mice with or without N. brasiliensis infection, suggesting that impairment of protection is dependent on IgE. These results indicate that the high levels of irrelevant IgE are beneficial for helminths and, alternatively, that anti-helminth IgE antibodies are protective for hosts. In addition, the impaired protection was found in IgE high-responder mice but not in low-responder mice, suggesting that protection against T. spiralis is controlled by IgE responsiveness in the host. Copyright © 2013 Elsevier B.V. All rights reserved.

Welfare Reform when Recipients Are Forward-Looking

ERIC Educational Resources Information Center

Swann, Christopher A.

2005-01-01

By studying recipients of aid under the Temporary Assistance for Needy Families (TANF) welfare scheme, the effect of time limits of welfare schemes on forward looking recipients is assessed using a discrete-choice dynamic programming framework model. The policy simulations for the preferred specification of utility reveal that two year time limits…

29 CFR 35.39 - Remedial action by recipient.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Enforcement Procedures § 35.39 Remedial action by recipient. Where CRC finds discrimination on the basis of age in violation of this Act or this part, the recipient shall take any remedial action that CRC deems...

Cloning Mice.

PubMed

Ogura, Atsuo

2017-08-01

Viable and fertile mice can be generated by somatic nuclear transfer into enucleated oocytes, presumably because the transplanted somatic cell genome becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring of mice were obtained by directly injecting donor nuclei into recipient enucleated oocytes. When this method is used (the so-called Honolulu method of somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely condense within the enucleated metaphase II-arrested oocytes, which contain high levels of M-phase-promoting factor (MPF). It is believed that the condensation of the donor chromosomes promotes complete reprogramming of the donor genome within the mouse oocytes. Another key to the success of mouse cloning is the use of blunt micropipettes attached to a piezo impact-driving micromanipulation device. This system saves a significant amount of time during the micromanipulation of oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a group of 20 oocytes can be enucleated within 10 min by an experienced operator. This protocol is composed of seven parts: (1) preparing micropipettes, (2) setting up the enucleation and injection micropipettes, (3) collecting and enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor nuclei, (6) activating embryos and culturing, and (7) transferring cloned embryos. © 2017 Cold Spring Harbor Laboratory Press.

Training NIH K Award Recipients: The Role of the Mentor

PubMed Central

Ripley, Elizabeth; Markowitz, Monika; Nichols‐Casebolt, Ann; Williams, Larry; Macrina, Francis

2012-01-01

Abstract Mentors play important roles in training new investigators. This study was designed to determine characteristics of NIH mentored K award recipients and their mentors, their interpersonal interactions, and the factors, which influence satisfaction within this relationship. Method: A survey of 3027 NIH mentored K recipients and 1384 mentors was conducted in 2009. Nine hundred twenty‐nine (30.7%) of the K recipients and 448 (32.4%) mentors completed the survey. Results: The gender of K respondents was evenly divided while the mentors were 72.1% male. The overall rating of their mentors was positive. Ideally, both thought the mentor should be important in research training; however, in actual practice, both rated the importance as lower. A total of 88.2% of recipients were satisfied with their relationship. Although the number of black K recipients was low, this group was more likely to be dissatisfied with the mentor relationship (6/29 or 20.7%) than their white counterparts. The frequency of meeting or communicating was correlated with K recipient satisfaction. Conclusions: Overall K recipients are satisfied with their mentor relationships. Although the number of black K recipient respondents was small, the higher level of mentor dissatisfaction should be further evaluated. Qualities of mentors, including the frequency of interactions and accessibility, can influence satisfaction. Clin Trans Sci 2012; Volume 5: 386–393 PMID:23067350

Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

PubMed

Zeytin, Hasan E; Patel, Arti C; Rogers, Connie J; Canter, Daniel; Hursting, Stephen D; Schlom, Jeffrey; Greiner, John W

2004-05-15

The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been

Long-term pulmonary infections in heart transplant recipients.

PubMed

Küpeli, Elif; Ulubay, Gaye; Akkurt, Esma Sevil; Öner Eyüboğlu, Füsun; Sezgin, Atilla

2015-04-01

Pulmonary infections are life-threatening complications in heart transplant recipients. Our aim was to evaluate long-term pulmonary infections and the effect of prophylactic antimicrobial strategies on time of occurrence of pulmonary infections in heart transplant recipients. Patients who underwent heart transplantation between 2003 and 2013 at Baskent University were reviewed. Demographic information and data about immunosuppression and infectious episodes were collected. In 82 heart transplant recipients (mean age, 33.85 y; 58 male and 24 female), 13 recipients (15.8%) developed pulmonary infections (mean age, 44.3 y; 9 male and 4 female). There were 12 patients who had dilated cardiomyopathy and 1 patient who had myocarditis before heart transplantation; 12 patients received immunosuppressive therapy in single or combination form. Pulmonary infections developed in the first month (1 patient), from first to third month (6 patients), from third to sixth month (1 patient), and > 6 months after transplantation (5 patients). Chest computed tomography showed consolidation (unilateral, 9 patients; bilateral, 4 patients). Multiple nodular consolidations were observed in 2 patients and a cavitary lesion was detected in 1 patient. Bronchoscopy was performed in 6 patients; 3 patients had Aspergillus fumigatus growth in bronchoalveolar lavage fluid, and 2 patients had Acinetobacter baumannii growth in sputum. Treatment was empiric antibiotics (6 patients), antifungal drugs (5 patients), and both antibiotics and antifungal drugs (2 patients); treatment period was 1-12 months in patients with invasive pulmonary aspergillosis. Pulmonary infections are the most common cause of mortality in heart transplant recipients. A. fumigatus is the most common opportunistic pathogen. Heart transplant recipients with fever and cough should be evaluated for pulmonary infections, and invasive pulmonary aspergillosis should be suspected if these symptoms occur within the first 3 months

Antithymocyte antibody-induced coagulopathy in renal transplant recipients.

PubMed

Siparsky, N F; Klein, R; Kushnir, L F; Gallichio, M H; Conti, D J

2013-05-01

Antithymocyte antibody (ATA) remains the most commonly used induction immunosuppressive agent in renal transplantation (RT). To date, few case reports of ATA-induced coagulopathy exist. We performed a single-center, retrospective analysis of renal transplant recipients (RTRs) who underwent RT followed by ATA therapy between 2007 and 2011. The protocol used for deceased donor and unrelated living donor recipient immunosuppression was Thymoglobulin (TMG), methylprednisolone, Cellcept, Prograf, and Rapamune. In related living donor recipients, Simulect (SIM) was substituted for TMG. The international normalized ratio (INR) was routinely checked on days 0 and 2, and thereafter at the discretion of the surgeon. RTRs were transfused packed red blood cells (PRBCs) or fresh frozen plasma (FFP) at the discretion of the surgeon. During the study period, 257 RTs were performed at our institution. The following 18 RTR were excluded: simultaneous kidney and pancreas transplant recipients (4), RTRs on warfarin at the time of admission (2), RTRs who received OKT3 (2), and RTRs with INR ≥ 1.2 at the time of admission (10). Of the remaining 239 RTR, 208 (87%) underwent TMG induction therapy; 31 RTR (13%) underwent SIM induction therapy. The mean INR peaked in both groups on day 4 but was higher in TMG recipients (TMG 1.35, SIM 1.20). FFP was transfused in 65 TMG (31%) and 3 SIM (10%) recipients (P = .01); PRBCs were transfused in 88 TMG (44%) and 6 SIM (19%) recipients (P = .02). No patients returned to the operating room for bleeding complications within 7 days of RT. Patient age, gender, ethnicity, and diabetes status were not statistically significant factors in the development of coagulopathy. TMG administration is associated with coagulopathy. Using an INR screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group. Copyright © 2013 Elsevier Inc. All rights reserved.

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

PubMed

Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

2018-04-10

Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model

PubMed Central

Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W.; Kasper, Dennis L.

1998-01-01

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules. PMID:9573085

Cyclosporine A impairs the macrophage reverse cholesterol transport in mice by reducing sterol fecal excretion.

PubMed

Zanotti, Ilaria; Greco, Daniela; Lusardi, Giulia; Zimetti, Francesca; Potì, Francesco; Arnaboldi, Lorenzo; Corsini, Alberto; Bernini, Franco

2013-01-01

Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

PubMed Central

Hsiao, K K; Groth, D; Scott, M; Yang, S L; Serban, H; Rapp, D; Foster, D; Torchia, M; Dearmond, S J; Prusiner, S B

1994-01-01

Two lines of transgenic (Tg) mice expressing high (H) levels of the mutant P101L prion protein (PrP) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogenates from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD-1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximately 10% of hamsters and approximately 40% of the Tg196 mice manifested neurologic signs between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated with brain extracts, producing incubation times of approximately 400 and approximately 75 days, respectively. Although the Tg(MoPrP-P101L)H mice appear to accumulate only low levels of infections prions in their brains, the serial transmission of disease to inoculated recipients argues that prion formation occurs de novo in the brains of these uninoculated animals. These Tg mouse studies, taken together with similar findings in humans dying of inherited prion diseases, provide additional evidence that prions lack a foreign nucleic acid. Images PMID:7916462

Functional antigen binding by the defective B cells of CBA/N mice.

PubMed

Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

1982-01-01

CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

PubMed Central

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

2015-01-01

Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects. Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by

20 CFR 627.503 - Recipient-level review.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recipient-level review. 627.503 Section 627... GOVERNING PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Grievances Procedures at the State and Local Level § 627.503 Recipient-level review. (a) If a complainant does not receive a decision at the SDA or the SSG...

Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

PubMed

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to

Hepatic Tissue Environment in NEMO-Deficient Mice Critically Regulates Positive Selection of Donor Cells after Hepatocyte Transplantation

PubMed Central

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Background Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Methods Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Results Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. Conclusion This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for

Naive Bayes as opinion classifier to evaluate students satisfaction based on student sentiment in Twitter Social Media

NASA Astrophysics Data System (ADS)

Candra Permana, Fahmi; Rosmansyah, Yusep; Setiawan Abdullah, Atje

2017-10-01

Students activity on social media can provide implicit knowledge and new perspectives for an educational system. Sentiment analysis is a part of text mining that can help to analyze and classify the opinion data. This research uses text mining and naive Bayes method as opinion classifier, to be used as an alternative methods in the process of evaluating studentss satisfaction for educational institution. Based on test results, this system can determine the opinion classification in Bahasa Indonesia using naive Bayes as opinion classifier with accuracy level of 84% correct, and the comparison between the existing system and the proposed system to evaluate students satisfaction in learning process, there is only a difference of 16.49%.

BK virus-associated hemorrhagic cystitis in a pediatric lung transplant recipient.

PubMed

Elidemir, Okan; Chang, I-Fen; Schecter, Marc G; Mallory, George B

2007-11-01

BKV was first postulated to be a potential pathogen in 1971 when it was isolated in the urine of a renal transplant recipient. The pathology of BKV is generally confined to the urinary tract. In renal transplant recipients, BKV has been associated with hemorrhagic cystitis, urethral stenosis, and interstitial nephritis. Reports of BKV infection in lung transplant recipients are limited to a few case reports in adult patients. A recent report revealed that up to 32% of adult lung transplant recipients may shed BKV in their urine without symptoms or renal dysfunction. To our knowledge, there are no published reports of pediatric lung transplant recipients with BKV-associated hematuria. We hereby report a case of BKV-induced hemorrhagic cystitis in a pediatric lung transplant recipient.

Travel and transplantation: travel-related diseases in transplant recipients.

PubMed

Kotton, Camille N

2012-12-01

Travel-related diseases may be seen in transplant recipients after travel, after transplant tourism, and via transmission from blood and organ donors, augmented by recent increases in travel, migration, and globalization. Such infections include tuberculosis, Plasmodium (malaria), Babesia, Trypanosoma cruzi (Chagas disease), Strongyloides, Coccidioides, Histoplasma, Leishmania, Brucella, HTLV, dengue, among numerous others. Review of cohorts of transplant recipients show that they tend to have minimal or suboptimal preparation prior to travel, with limited pretravel vaccination, medications, and education, which poses a greatly increased risk of travel-related infections and complications. The epidemiology of such travel-related infections in transplant recipients, along with methods for prevention, including vaccines, chemoprophylaxis, and education may help SOT recipients avoid travel-related infections, and are discussed in this review. Optimizing the understanding of the risk of tropical, geographically restricted, and other unusual or unexpected, travel-related infections will enhance the safety of vulnerable transplant recipients from potentially life-threatening infections.

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

PubMed

Sugimoto, Seiichiro; Yamane, Masaomi; Otani, Shinji; Kurosaki, Takeshi; Okahara, Shuji; Hikasa, Yukiko; Toyooka, Shinichi; Kobayashi, Motomu; Oto, Takahiro

2018-04-21

Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

An Analysis of Past Surgical Infection Society Award Recipients.

PubMed

Claridge, Jeffrey A; Banerjee, Aman; Zosa, Brenda M; Hydo, Lynn J; Lipsett, Pamela A; Barie, Philip S

2016-06-01

The Surgical Infection Society (SIS) through its foundation (FDTN) confers awards to individuals who demonstrate interest in researching infection in the surgical setting. We sought to characterize the research output from prior award recipients and determine the impact of these awards on the individual and the SIS. The SIS website was queried for the names of all past award recipients. A MEDLINE search of the recipients was performed. Total number of publications and publications in the society's journal, Surgical Infections (SI), were identified. Gender and leadership positions within SIS were determined. Meeting attendance and participation were assessed. Donations by scholarship recipient to the FDTN were evaluated. Between 1984 and 2012, 116 individuals received an SIS award or scholarship. Of these, 72% were male. There were 101 scholarships awarded, totaling nearly $3 million. Of the 19 new Junior Faculty Scholarships awarded, four were to consecutive recipients (CR). There were 11 clinical evaluative award scholarships awarded, three to CR. There were 100 Resident/Fellow scholarships awarded, and of these, 22 were awarded to CR. Past recipients had multiple publications (median total publications = 27; interquartile range (IQR): Nine to 62) and published multiple papers on the topic for which they received an award (median two; IQR: Zero to four). Recipients did not publish in SI (median SI publications = zero; IQR: Zero to one). There was no substantial difference in the number of publications by gender. Multiple awards (MA) were conferred to 26 (22%) individuals. Six (5.1%) assumed an executive position within SIS, two (1.7%) became SIS president. Those who received MA were more likely to serve as an officer than those who only received one award (15% vs. 2%, p = 0.02). Scholarships have a large benefit for individual recipients; however, the benefit to the society remains harder to quantify.

AMS/DOE Fellowship Recipients

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

Armstrong, Stephanie

The AMS/DOE graduate fellowships were awarded to three students entering their first year of graduate study. The funds allowed each student to take a full course load during their first of year of graduate study which helps each of them to enter the professional, scientific community at an earlier date. Each recipient is academically outstanding, received glowing references of support and demonstrated their strong desire to perform scientific research. As part of the fellowship, each of the students was invited to attend the AMS Annual Meeting where they got to participate in the AMS student conference, attend scientific sessions andmore » visit the exhibition hall. In addition, a student awards luncheon was held where each of the recipients got to meet their sponsor and receive a certificate.« less

Sexual concerns among kidney transplant recipients.

PubMed

Muehrer, Rebecca J; Lanuza, Dorothy M; Brown, Roger L; Djamali, Arjang

2014-11-01

Little is known about the specific sexual concerns of kidney transplant (KTx) recipients. The primary objectives of this study were to: (i) describe the importance of sexuality to KTx recipients; (ii) investigate the sexual concerns of KTx recipients; and (iii) examine the relationship between sexual concerns and quality of life (QOL). A secondary objective was to examine potential sexual concern differences by gender, pre-transplant dialysis status, and donor type. This study employed a cross-sectional, descriptive, correlational design. Sexual concerns were identified using the Sexual Concerns Questionnaire, which contains seven subscales. QOL was measured with the SF-8 and the QOL Uniscale. Nearly 73% of subjects rated sexuality as important. Subscales indicating highest area of sexual concerns were communication with healthcare providers about sexuality (Mean (M) = 2.70) and sexual pleasure concerns (M = 2.45). Higher concern ratings regarding health consequences of sexual activity, quality of sexual relationship, sexual pleasure, sexual functioning problems, and pessimistic beliefs about treatment were significantly, inversely related to QOL. Women had significantly higher scores on the Sexual Pleasure and Communication with Healthcare Providers subscales than men. This study reports the sexual concerns of KTx recipients' who are an average of four yr since surgery, and the relationship of these concerns to QOL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

45 CFR 90.49 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Remedial and affirmative action by recipients. 90..., Conciliation and Enforcement Procedures § 90.49 Remedial and affirmative action by recipients. (a) Where a... remedial action. (b) Even in the absence of a finding of discrimination, a recipient may take affirmative...

24 CFR 146.47 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Remedial and affirmative action by... Remedial and affirmative action by recipients. (a) Where the Secretary finds that a recipient has... action. (b) Even in the absence of a finding of discrimination, a recipient may take affirmative action...

24 CFR 146.47 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Remedial and affirmative action by... Remedial and affirmative action by recipients. (a) Where the Secretary finds that a recipient has... action. (b) Even in the absence of a finding of discrimination, a recipient may take affirmative action...

45 CFR 90.49 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Remedial and affirmative action by recipients. 90..., Conciliation and Enforcement Procedures § 90.49 Remedial and affirmative action by recipients. (a) Where a... remedial action. (b) Even in the absence of a finding of discrimination, a recipient may take affirmative...

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

PubMed

Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

2018-04-15

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 (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 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 the

45 CFR 617.14 - Remedial action by recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

....14 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF... the effects of the discrimination. If another recipient exercises control over the recipient that has...

45 CFR 617.14 - Remedial action by recipients.

Code of Federal Regulations, 2011 CFR

2011-10-01

....14 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF... the effects of the discrimination. If another recipient exercises control over the recipient that has...

Living donation decision making: recipients' concerns and educational needs.

PubMed

Waterman, Amy D; Stanley, Sara L; Covelli, Tonie; Hazel, Erik; Hong, Barry A; Brennan, Daniel C

2006-03-01

Despite the advantages of living donor transplantation, evidence suggests that some potential recipients with living donors have psychological concerns that prevent them from pursuing living donation. Addressing these concerns through education may increase the rates of living donation. To understand the psychological barriers and educational needs of potential kidney recipients regarding living donation. Qualitative focus group study of kidney transplant recipients, donors, and family members to explore their assessment of the advantages of dialysis and deceased donor transplantation over living donation, their concerns about living donation, and what types of living donation education would be most helpful. Kidney recipients reported that they might not pursue living donation because they felt guilty and indebted to the donor, did not want to harm or inconvenience the donor, did not want to accept a kidney that a family member might need later, and did not want to disappoint the donor if the kidney failed. Recipients were generally unaware that donors could personally benefit from donating and would rather wait for donor volunteers than ask anyone directly. Both donors and recipients thought that training on how to make the donation request and education about living donors' motivations for donation and transplant experience could help more renal patients pursue living donation.

Long-term outcomes and management of lung transplant recipients.

PubMed

Costa, Joseph; Benvenuto, Luke J; Sonett, Joshua R

2017-06-01

Lung transplantation is an established treatment for patients with end-stage lung disease. Improvements in immunosuppression and therapeutic management of infections have resulted in improved long-term survival and a decline in allograft rejection. Allograft rejection continues to be a serious complication following lung transplantation, thereby leading to acute graft failure and, subsequently, chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS), the most common phenotype of CLAD, is the leading cause of late mortality and morbidity in lung recipients, with 50% having developed BOS within 5 years of lung transplantation. Infections in lung transplant recipients are also a significant complication and represent the most common cause of death within the first year. The success of lung transplantation depends on careful management of immunosuppressive regimens to reduce the rate of rejection, while monitoring recipients for infections and complications to help identify problems early. The long-term outcomes and management of lung transplant recipients are critically based on modulating natural immune response of the recipient to prevent acute and chronic rejection. Understanding the immune mechanisms and temporal correlation of acute and chronic rejection is thus critical in the long-term management of lung recipients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adiponectin deficiency suppresses lymphoma growth in mice by modulating NK cells, CD8 T cells, and myeloid-derived suppressor cells.

PubMed

Han, Sora; Jeong, Ae Lee; Lee, Sunyi; Park, Jeong Su; Kim, Kwang Dong; Choi, Inpyo; Yoon, Suk Ran; Lee, Myung Sok; Lim, Jong-Seok; Han, Seung Hyun; Yoon, Do Young; Yang, Young

2013-05-01

Previously, we found that adiponectin (APN) suppresses IL-2-induced NK cell activation by downregulating the expression of the IFN-γ-inducible TNF-related apoptosis-inducing ligand and Fas ligand. Although the antitumor function of APN has been reported in several types of solid tumors, with few controversial results, no lymphoma studies have been conducted. In this study, we assessed the role of APN in immune cell function, including NK cells, CTLs, and myeloid-derived suppressor cells, in EL4 and B16F10 tumor-bearing APN knockout (KO) mice. We observed attenuated EL4 growth in the APNKO mice. Increased numbers of splenic NK cells and splenic CTLs were identified under naive conditions and EL4-challenged conditions, respectively. In APNKO mice, splenic NK cells showed enhanced cytotoxicity with and without IL-2 stimulation. Additionally, there were decreased levels of myeloid-derived suppressor cell accumulation in the EL4-bearing APNKO mice. Enforced MHC class I expression on B16F10 cells led to attenuated growth of these tumors in APNKO mice. Thus, our results suggest that EL4 regression in APNKO mice is not only due to an enhanced antitumor immune response but also to a high level of MHC class I expression.

PARACOCCIDIOIDOMYCOSIS IN A RENAL TRANSPLANT RECIPIENT

PubMed Central

GÓES, Heliana Freitas de Oliveira; DURÃES, Sandra Maria Barbosa; LIMA, Caren dos Santos; de SOUZA, Mariana Boechat; VILAR, Enoi Aparecida Guedes; DALSTON, Marcos Olivier

2016-01-01

Paracoccidioidomycosis (PCM) is the most common endemic mycosis in Latin America. The etiological agents, which comprise two species, Paracoccidioides brasiliensis and P. lutzii, are thermodimorphic fungi that usually affect previously healthy adults. They primarily involve the lungs and then disseminate to other organs. Such mycosis is rare in organ transplant recipients; there have been only three cases reported in literature, until now. We report a case of PCM in a renal transplant recipient with an unusual dermatological presentation. PMID:26910451

Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

PubMed

Vandekerckhove, Linos; Verhofstede, Chris; Vogelaers, Dirk

2009-06-01

Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

10 CFR 1060.201 - Relatives, contractors, and assistance award recipients.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Relatives, contractors, and assistance award recipients... under § 1060.101(a)(1), a DOE contractor or a DOE assistance award recipient or the employee of a DOE contractor or a DOE assistance award recipient unless the travel expenses are incurred with respect to...

10 CFR 1060.201 - Relatives, contractors, and assistance award recipients.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Relatives, contractors, and assistance award recipients... under § 1060.101(a)(1), a DOE contractor or a DOE assistance award recipient or the employee of a DOE contractor or a DOE assistance award recipient unless the travel expenses are incurred with respect to...

10 CFR 1060.201 - Relatives, contractors, and assistance award recipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Relatives, contractors, and assistance award recipients... under § 1060.101(a)(1), a DOE contractor or a DOE assistance award recipient or the employee of a DOE contractor or a DOE assistance award recipient unless the travel expenses are incurred with respect to...

10 CFR 1060.201 - Relatives, contractors, and assistance award recipients.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Relatives, contractors, and assistance award recipients... under § 1060.101(a)(1), a DOE contractor or a DOE assistance award recipient or the employee of a DOE contractor or a DOE assistance award recipient unless the travel expenses are incurred with respect to...

10 CFR 1060.201 - Relatives, contractors, and assistance award recipients.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Relatives, contractors, and assistance award recipients... under § 1060.101(a)(1), a DOE contractor or a DOE assistance award recipient or the employee of a DOE contractor or a DOE assistance award recipient unless the travel expenses are incurred with respect to...

13 CFR 117.6 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Remedial and affirmative action by... 1975, AS AMENDED § 117.6 Remedial and affirmative action by recipients. (a) Where a recipient is found...) Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome...

13 CFR 117.6 - Remedial and affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Remedial and affirmative action by... 1975, AS AMENDED § 117.6 Remedial and affirmative action by recipients. (a) Where a recipient is found...) Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome...

Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice.

PubMed

Farace, Francoise; Prestoz, Laetitita; Badaoui, Sabrina; Guillier, Martine; Haond, Celine; Opolon, Paule; Thomas, Jean-Leon; Zalc, Bernard; Vainchenker, William; Turhan, Ali G

2004-02-01

Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.

Self-Management in Liver Transplant Recipients: A Narrative Review.

PubMed

Ko, Dami; Muehrer, Rebecca J; Bratzke, Lisa C

2018-06-01

Although self-management is essential for liver transplant recipients, there is no review that has synthesized findings related to self-management in this population. This narrative review aimed to synthesize the current findings and identify the gaps in knowledge about self-management in liver recipients. A search of PubMed, CINAHL Plus, PsychINFO, ProQuest, and Web of Science was conducted using the following terms: [Self-care OR Self-management OR Health behavior] AND [Liver transplantation]. Peer-reviewed published research articles focusing on self-management of adult recipients were selected. A total of 23 articles were included for review. Two reviewers independently reviewed the full text of selected articles and extracted the data about definitions, measurements, and findings regarding self-management. Three areas of self-management were identified, including medication nonadherence (n = 11), alcohol recidivism (n = 11), and health maintenance (n = 5). Reported rates of medication nonadherence ranged from 8% to 66%. Medication nonadherence was related to recipients' demographic (eg, age or sex), transplant-related (eg, time since transplant), and pretransplant variables (eg, history of substance/alcohol abuse). Reported alcohol recidivism rates ranged from 3% to 95%. Age, pretransplant variables (eg, abstinent time before transplant), and personality disorder were identified to be related to alcohol recidivism after transplant. The health maintenance studies discussed behaviors such as smoking, clinic appointment attendance, or vaccination/health screening behaviors of recipients. Self-management studies in liver recipients have been narrowly focused on medication nonadherence and alcohol recidivism. To improve self-management in recipients, self-management beyond medication nonadherence and alcohol recidivism should be comprehensively examined.

32 CFR 37.850 - Should I require recipients to mark data?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Intellectual Property § 37.850 Should I require recipients to mark data? To protect the recipient's interests in data, your TIA should require the recipient to mark any particular data that it wishes to protect...

28 CFR 42.505 - Administrative requirements for recipients.

Code of Federal Regulations, 2012 CFR

2012-07-01

... recipients. 42.505 Section 42.505 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL... a recipient has discriminated against persons on the basis of handicap in violation of section 504... overcome the effects of the discrimination. This may include remedial action with respect to handicapped...

45 CFR 1643.5 - Recipient policies and recordkeeping.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

45 CFR 1643.5 - Recipient policies and recordkeeping.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

45 CFR 1643.5 - Recipient policies and recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

45 CFR 1643.5 - Recipient policies and recordkeeping.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

45 CFR 1643.5 - Recipient policies and recordkeeping.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

Management of toxoplasmosis in transplant recipients: an update.

PubMed

Dard, Céline; Marty, Pierre; Brenier-Pinchart, Marie-Pierre; Garnaud, Cécile; Fricker-Hidalgo, Hélène; Pelloux, Hervé; Pomares, Christelle

2018-06-01

Toxoplasmosis is a life-threatening parasitic disease for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The risk of toxoplasmosis in transplant patients mainly depends on the degree of immunosuppression, the tropism of Toxoplasma gondii for the grafted tissue, and the seroprevalence in the general population. Although transplant recipients with toxoplasmosis have a high mortality rate, there are neither well-defined recommendations nor a consensus for the management of this disease in these patients. Areas covered. This review focuses on the management of toxoplasmosis in transplant recipients and discusses the various strategies for diagnosis, prevention, treatment, and follow-up in clinical practice. The literature search was conducted on publications in English and French using the search terms "Toxoplasma gondii", "organ transplant" and "transplant recipients". Expert commentary. The diagnosis of toxoplasmosis has greatly improved over the last two decades, in part due to molecular techniques, but it is still a fatal illness. Non-specificity of the symptoms, resulting in a delay before diagnosis, and therapeutic failure are the main causes of death. The development of active treatments against cysts is one of the current challenges that will considerably improve the management of toxoplasmosis in transplant recipients by clearing chronic infection to avoid T. gondii reactivation.

Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice

PubMed Central

Uz, Tolga; Dimitrijevic, Nikola; Imbesi, Marta; Manev, Hari; Manev, Radmila

2008-01-01

A common biological pathway may contribute to the comorbidity of atherosclerosis and depression. Increased activity of the enzymatic 5-lipoxygenase (5-LOX; 5LO) pathway is a contributing factor in atherosclerosis and a 5-LOX inhibitor, MK-886, is beneficial in animal models of atherosclerosis. In the brain, MK-886 increases phosphorylation of the glutamate receptor subunit GluR1, and the increased phosphorylation of this receptor has been associated with antidepressant treatment. In this work, we evaluated the behavioral effects of MK-886 in an automated assay of mouse forced swimming, which identifies antidepressant activity as increased climbing behavior and/or decreased rest time. Whereas a single injection of MK-886 (3 and 10 mg/kg) did not affect forced swimming behaviors assayed 30 min later, 6 daily injections of 3 mg/kg MK-886 slightly increased climbing and significantly reduced rest time in wild-type mice but not in 5-LOX-deficient mice. A diet delivery of MK-886, 4 μg per 100 mg body-weight per day, required three weeks to affect forced swimming; it increased climbing behavior. Climbing behavior was also increased in naive 5-LOX-deficient mice compared to naive wild-type controls. These results suggest that 5-LOX inhibition and deficiency may be associated with antidepressant activity. Increased climbing in a forced swimming assay is a typical outcome of antidepressants that increase noradrenergic and dopaminergic activity. Interestingly, 5-LOX deficiency and MK-886 treatment have been shown to be capable of increasing the behavioral effects of a noradrenaline/dopamine-potentiating drug, cocaine. Future research is needed to evaluate the clinical relevance of our findings. PMID:18403121

Securing recipiency in workplace meetings: Multimodal practices

PubMed Central

Ford, Cecilia E.; Stickle, Trini

2013-01-01

As multiparty interactions with single courses of coordinated action, workplace meetings place particular interactional demands on participants who are not primary speakers (e.g. not chairs) as they work to initiate turns and to interactively coordinate with displays of recipiency from co-participants. Drawing from a corpus of 26 hours of videotaped workplace meetings in a midsized US city, this article reports on multimodal practices – phonetic, prosodic, and bodily-visual – used for coordinating turn transition and for consolidating recipiency in these specialized speech exchange systems. Practices used by self-selecting non-primary speakers as they secure turns in meetings include displays of close monitoring of current speakers’ emerging turn structure, displays of heightened interest as current turns approach possible completion, and turn initiation practices designed to pursue and, in a fine-tuned manner, coordinate with displays of recipiency on the parts of other participants as well as from reflexively constructed ‘target’ recipients. By attending to bodily-visual action, as well as phonetics and prosody, this study contributes to expanding accounts for turn taking beyond traditional word-based grammar (i.e. lexicon and syntax). PMID:24976789

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

PubMed

Martinez-Selles, Manuel; Almenar, Luis; Paniagua-Martin, Maria J; Segovia, Javier; Delgado, Juan F; Arizón, Jose M; Ayesta, Ana; Lage, Ernesto; Brossa, Vicens; Manito, Nicolás; Pérez-Villa, Félix; Diaz-Molina, Beatriz; Rábago, Gregorio; Blasco-Peiró, Teresa; De La Fuente Galán, Luis; Pascual-Figal, Domingo; Gonzalez-Vilchez, Francisco

2015-03-01

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women. © 2014 Steunstichting ESOT.

Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database.

PubMed

Karafin, Matthew S; Bruhn, Roberta; Westlake, Matt; Sullivan, Marian T; Bialkowski, Walter; Edgren, Gustaf; Roubinian, Nareg H; Hauser, Ronald G; Kor, Daryl J; Fleischmann, Debra; Gottschall, Jerome L; Murphy, Edward L; Triulzi, Darrell J

2017-12-01

Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers. © 2017 AABB.

A Novel Model on DST-Induced Transplantation Tolerance by the Transfer of Self-Specific Donor tTregs to a Haplotype-Matched Organ Recipient

PubMed Central

Mohr Gregoriussen, Angelica Maria; Bohr, Henrik Georg

2017-01-01

Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades and are not yet fully elucidated. Once we discover how the details of the mechanisms involved are linked, we could be within reach of a procedure making it possible to establish donor-specific tolerance with minimal or no immunosuppressive medication. Today, it is well established that CD4+Foxp3+ regulatory T cells (Tregs) are indispensable for maintaining immunological self-tolerance. A large number of animal studies have also shown that Tregs are essential for establishing and maintaining transplantation tolerance. In this paper, we present a hypothesis of one H2-haplotype-matched DST-induced transplantation tolerance (in mice). The formulated hypothesis is based on a re-interpretation of data from an immunogenetic experiment published by Niimi and colleagues in 2000. It is of importance that the naïve recipient mice in this study were never immunosuppressed and were therefore fully immune competent during the course of tolerance induction. Based on the immunological status of the recipients, we suggest that one H2-haplotype-matched self-specific Tregs derived from the transfusion blood can be activated and multiply in the host by binding to antigen-presenting cells presenting allopeptides in their major histocompatibility complex (MHC) class II (MHC-II). We also suggest that the endothelial and epithelial cells within the solid organ allograft upregulate the expression of MHC-II and attract the expanded Treg population to suppress inflammation within the graft. We further suggest that this biological process, here termed MHC-II recruitment, is a vital survival mechanism for organs (or the organism in general) when attacked by an immune system. PMID:28270810

Survival of blood transfusion recipients identified by a look-back investigation.

PubMed

Dorsey, Kerri A; Moritz, Erin D; Notari, Edward P; Schonberger, Lawrence B; Dodd, Roger Y

2014-01-01

Survival of blood transfusion recipients is a critical consideration in assessing the outcomes of transfusion. Data from the USA on the short- and long-term survival of recipients are limited. Blood product recipients were identified through a look-back study of Creutzfeldt-Jakob disease. Survival data were obtained from searches of the National Death Index or the Social Security Death Master File. Short- and long-term survival of recipients was analysed through descriptive statistics, Kaplan-Meier survival analysis, and stratified Cox proportional hazard modelling. This study includes data from 575 blood product recipients. One half of the recipients died within the first year of transfusion and the median time to death was 1.1 years. Survival rates at 5, 10, 15, 20, and 25 years after transfusion were 32%, 22%, 15%, 12%, and 9%, respectively. Survival rates varied with age at transfusion and type of component received, but not by gender. Survival after transfusion varied by year of transfusion, with recipients transfused in 1980-1989 having longer post-transfusion survival than those transfused in 2000-2010 (p=0.049). In multivariate models, the type of component transfused, but not the year of transfusion, was a significant predictor of survival among recipients; this effect varied by age. We provide an estimate of survival time from a geographically diverse sample of blood product recipients in the USA. Predictors of post-transfusion survival are numerous and complex, and may include year of transfusion and type of component transfused.

45 CFR 617.4 - General duties of recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... subrecipients, and the instrument under which the Federal financial assistance is passed to the subrecipient... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF § 617.4 General duties of recipients. Each recipient of Federal financial assistance from NSF shall...

Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan.

PubMed

Lee, Kwai-Fong; Tsai, Yi-Ting; Lin, Chih-Yuan; Hsieh, Chung-Bao; Wu, Sheng-Tang; Ke, Hung-Yen; Lin, Yi-Chang; Lin, Feng-Yen; Lee, Wei-Hwa; Tsai, Chien-Sung

2016-01-01

Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study

PubMed Central

Agniel, Denis; Beam, Andrew; Yorkgitis, Brian; Bicket, Mark; Homer, Mark; Fox, Kathe P; Knecht, Daniel B; McMahill-Walraven, Cheryl N; Palmer, Nathan; Kohane, Isaac

2018-01-01

Abstract Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact. PMID:29343479

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

PubMed Central

Limsreng, Setha; Him, Sovanvatey; Nouhin, Janin; Hak, Chanroeurn; Srun, Chanvatey; Viretto, Gerald; Ouk, Vara; Delfraissy, Jean Francois; Ségéral, Olivier

2014-01-01

Introduction In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. Methods This retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. Results On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. Conclusion In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for

Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

PubMed

Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

2013-01-01

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

Preventative Effect of an Herbal Preparation (HemoHIM) on Development of Airway Inflammation in Mice via Modulation of Th1/2 Cells Differentiation

PubMed Central

Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

2013-01-01

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4+ T cells displayed increased Th1 (IFN-γ+ cell) as well as decreased Th2 (IL-4+ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

Simple scaling of cooperation in donor-recipient games.

PubMed

Berger, Ulrich

2009-09-01

We present a simple argument which proves a general version of the scaling phenomenon recently observed in donor-recipient games by Tanimoto [Tanimoto, J., 2009. A simple scaling of the effectiveness of supporting mutual cooperation in donor-recipient games by various reciprocity mechanisms. BioSystems 96, 29-34].

24 CFR 135.32 - Responsibilities of the recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Responsibilities of the recipient... EMPLOYMENT AND BUSINESS OPPORTUNITY ECONOMIC OPPORTUNITIES FOR LOW- AND VERY LOW-INCOME PERSONS Economic Opportunities for Section 3 Residents and Section 3 Business Concerns § 135.32 Responsibilities of the recipient...

44 CFR 7.924 - Affirmative action by recipient.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Affirmative action by... Standards for Determining Age Discrimination § 7.924 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of...

44 CFR 7.924 - Affirmative action by recipient.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Affirmative action by... Standards for Determining Age Discrimination § 7.924 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of...

Urinary tract infection in kidney transplant recipients.

PubMed

Chacón-Mora, Natalia; Pachón Díaz, Jerónimo; Cordero Matía, Elisa

2017-04-01

Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence from 25% to 75%, varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought reviews the incidence and importance of urinary tract infection on graft survival, the microbiology with special emphasis on multidrug resistant microorganisms, the therapeutic management of UTI and the prophylaxis of recurrent UTI among solid organ transplant recipients, highlighting the need for prospective clinical trials to unify the clinical management in this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

MUSIC APPRECIATION AND TRAINING FOR COCHLEAR IMPLANT RECIPIENTS: A REVIEW

PubMed Central

Looi, Valerie; Gfeller, Kate; Driscoll, Virginia

2012-01-01

In recent years, there has been increasing interest in music perception of cochlear implant (CI) recipients, and a growing body of research conducted in this area. The majority of these studies have examined perceptual accuracy for pitch, rhythm, and timbre. Another important, but less commonly studied aspect of music listening is appreciation, or appraisal. Despite the ongoing research into potential technological improvements that may improve music perception for recipients, both perceptual accuracy and appreciation generally remain poor for most recipients. Whilst perceptual accuracy for music is important, appreciation and enjoyment also warrants research as it also contributes to clinical outcomes and perceived benefits. Music training is being shown to offer excellent potential for improving music perception and appreciation for recipients. Therefore, the primary topics of this review are music appreciation and training. However, a brief overview of the psychoacoustic, technical, and physiological factors associated with a recipient’s perception of music is provided, as these are important factors in understanding the listening experience for CI recipients. The purpose of this review is to summarize key papers that have investigated these issues, in order to demonstrate that i) music enjoyment and appraisal is an important and valid consideration in evaluating music outcomes for recipients, and ii) that music training can improve music listening for many recipients, and is something that can be offered to persons using current technology. PMID:23459244

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

Cognitive Performance Under Electroconvulsive Therapy (ECT) in ECT-Naive Treatment-Resistant Patients With Major Depressive Disorder.

PubMed

Ziegelmayer, Christoph; Hajak, Göran; Bauer, Anne; Held, Marion; Rupprecht, Rainer; Trapp, Wolfgang

2017-06-01

Although electroconvulsive therapy (ECT) is considered a safe and highly effective treatment option for major depressive disorder, there are still some reservations with regard to possible adverse cognitive adverse effects. This is the case despite a large body of evidence showing that these deficits are transient and that there even seems to be a long-term improvement of cognitive functioning level. However, most data concerning cognitive adverse effects stem from studies using mixed samples of treatment-resistant and non-treatment-resistant as well as ECT-naive and non-ECT-naive subjects. Furthermore, neurocognitive measures might partly be sensitive to practice effects and improvements in depressive symptom level. We examined neurocognitive performance in a sample of 20 treatment-resistant and ECT-naive subjects using repeatable neurocognitive tests, whereas changes in depressive symptom level were controlled. Cognitive functioning level was assessed before (baseline), 1 week, and 6 months (follow-up 1 and 2) after (12 to) 15 sessions of unilateral ECT treatment. No adverse cognitive effects were observed in any of the cognitive domains examined. Instead, a significant improvement in verbal working memory performance was found from baseline to follow-up 2. When changes in depressive symptom levels were controlled statistically, this improvement was no longer seen. Although findings that ECT does not lead to longer lasting cognitive deficits caused by ECT were confirmed, our study adds evidence that previous results of a beneficial effect of ECT on cognition might be questioned.

Donor-derived infections among Chinese donation after cardiac death liver recipients

PubMed Central

Ye, Qi-Fa; Zhou, Wei; Wan, Qi-Quan

2017-01-01

AIM To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients. METHODS We retrospectively studied the results of blood cultures among our donation after cardiac death (DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors’ and patients’ characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections. RESULTS Head trauma was the most common origin of death among our 67 DCD donors (46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria (70.6%). Only three (4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections, with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donor-derived infections showed relation to higher crude mortality and graft loss rates (33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections (9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy. CONCLUSION Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given. PMID:28883707

Association Between Spousal Caregiver Well-Being and Care Recipient Healthcare Expenditures.

PubMed

Ankuda, Claire K; Maust, Donovan T; Kabeto, Mohammed U; McCammon, Ryan J; Langa, Kenneth M; Levine, Deborah A

2017-10-01

To measure the association between spousal depression, general health, fatigue and sleep, and future care recipient healthcare expenditures and emergency department (ED) use. Prospective cohort study. Health and Retirement Study. Home-dwelling spousal dyads in which one individual (care recipient) was aged 65 and older and had one or more activity of daily living or instrumental activity of daily living disabilities and was enrolled in Medicare Part B (N = 3,101). Caregiver sleep (Jenkins Sleep Scale), depressive symptoms (Center for Epidemiologic Studies Depression-8 Scale), and self-reported general health measures. Primary outcome was care recipient Medicare expenditures. Secondary outcome was care recipient ED use. Follow-up was 6 months. Caregiver depressive symptoms score and six of 17 caregiver well-being measures were prospectively associated with higher care recipient expenditures after minimal adjustment (P < .05). Higher care recipient expenditures remained significantly associated with caregiver fatigue (cost increase, $1,937, 95% confidence interval (CI) = $770-3,105) and caregiver sadness (cost increase, $1,323, 95% CI = $228-2,419) after full adjustment. Four of 17 caregiver well-being measures, including severe fatigue, were significantly associated with care recipient ED use after minimal adjustment (P < .05). Greater odds of care recipient ED use remained significantly associated with caregiver fatigue (odds ratio (OR) = 1.24, 95% CI = 1.01-1.52) and caregiver fair to poor health (OR = 1.23, 95% CI = 1.04-1.45) after full adjustment. Caregiver total sleep score was not associated with care recipient outcomes. Poor caregiver well-being, particularly severe fatigue, is independently and prospectively associated with higher care recipient Medicare expenditures and ED use. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Donor-derived infections among Chinese donation after cardiac death liver recipients.

PubMed

Ye, Qi-Fa; Zhou, Wei; Wan, Qi-Quan

2017-08-21

To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients. We retrospectively studied the results of blood cultures among our donation after cardiac death (DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections. Head trauma was the most common origin of death among our 67 DCD donors (46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria (70.6%). Only three (4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections, with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donor-derived infections showed relation to higher crude mortality and graft loss rates (33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections (9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy. Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

Microenterprise Development: An Employment Option for Welfare Recipients.

ERIC Educational Resources Information Center

Friedman, Pamela

2001-01-01

This document examines microenterprise development as an employment option for Temporary Assistance for Needy Families (TANF) recipients. The document begins with a brief discussion of the feasibility of self-employment as an option for TANF recipients, particularly in a slow economy. The next section answers policy questions pertaining to the…

38 CFR 18.516 - Affirmative action by recipients.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Affirmative action by... Determining Age Discrimination § 18.516 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted in...

38 CFR 18.516 - Affirmative action by recipients.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Affirmative action by... Determining Age Discrimination § 18.516 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted in...

Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells*

PubMed Central

Honda, Arata; Hatori, Masanori; Hirose, Michiko; Honda, Chizumi; Izu, Haruna; Inoue, Kimiko; Hirasawa, Ryutaro; Matoba, Shogo; Togayachi, Sumie; Miyoshi, Hiroyuki; Ogura, Atsuo

2013-01-01

Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity. PMID:23880763

Personality matters: individual variation in reactions of naive bird predators to aposematic prey.

PubMed

Exnerová, Alice; Svádová, Katerina Hotová; Fucíková, Eva; Drent, Pieter; Stys, Pavel

2010-03-07

Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality--a complex of correlated, heritable behavioural traits consistent across contexts. In the great tit (Parus major), two extreme personality types have been defined. 'Fast' explorers are bold, aggressive and routine-forming; 'slow' explorers are shy, non-aggressive and innovative. Influence of personality type on unlearned reaction to aposematic prey, rate of avoidance learning and memory were tested in naive, hand-reared great tits from two opposite lines selected for exploration (slow against fast). The birds were subjected to a sequence of trials in which they were offered aposematic adult firebugs (Pyrrhocoris apterus). Slow birds showed a greater degree of unlearned wariness and learned to avoid the firebugs faster than fast birds. Although birds of both personality types remembered their experience, slow birds were more cautious in the memory test. We conclude that not only different species but also populations of predators that differ in proportions of personality types may have different impacts on survival of aposematic insects under natural conditions.

Graft-versus-host disease targets ovary and causes female infertility in mice.

PubMed

Shimoji, Sonoko; Hashimoto, Daigo; Tsujigiwa, Hidetsugu; Miyawaki, Kohta; Kato, Koji; Takahashi, Shuichiro; Ogasawara, Reiki; Jiromaru, Takashi; Iwasaki, Hiromi; Miyamoto, Toshihiro; Akashi, Koichi; Teshima, Takanori

2017-03-02

Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). Although pretransplant conditioning regimen has been appreciated as a cause of ovarian failure, increased application of reduced-intensity conditioning allowed us to revisit other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell-mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. Histological evaluation of the ovaries after SCT demonstrated donor T-cell infiltration in close proximity to apoptotic granulosa cells in the ovarian follicles, resulting in impaired follicular hormone production and maturation of ovarian follicles. Mating experiments showed that female recipients of allogeneic SCT deliver significantly fewer newborns than recipients of syngeneic SCT. GVHD-mediated ovary insufficiency and infertility were independent of conditioning. Pharmacologic GVHD prophylaxis protected the ovary from GVHD and preserved fertility. These results demonstrate for the first time that GVHD targets the ovary and impairs ovarian function and fertility and has important clinical implications in young female transplant recipients with nonmalignant diseases, in whom minimally toxic regimens are used. © 2017 by The American Society of Hematology.

20 CFR 416.1333 - Termination at the request of the recipient.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 416.1333 Section 416.1333 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY... request of the recipient. A recipient, his legal guardian, or his representative payee, may terminate his... would result if an eligible recipient were not covered by the supplemental security income program. When...

Gut microbiota can transfer fiber characteristics and lipid metabolic profiles of skeletal muscle from pigs to germ-free mice.

PubMed

Yan, Honglin; Diao, Hui; Xiao, Yi; Li, Wenxia; Yu, Bing; He, Jun; Yu, Jie; Zheng, Ping; Mao, Xiangbing; Luo, Yuheng; Zeng, Benhua; Wei, Hong; Chen, Daiwen

2016-08-22

Obesity causes changes in microbiota composition, and an altered gut microbiota can transfer obesity-associated phenotypes from donors to recipients. Obese Rongchang pigs (RP) exhibited distinct fiber characteristics and lipid metabolic profiles in their muscle compared with lean Yorkshire pigs (YP). However, whether RP have a different gut microbiota than YP and whether there is a relationship between the microbiota and muscle properties are poorly understood. The present study was conducted to test whether the muscle properties can be transferred from pigs to germ-free (GF) mice. High-throughput pyrosequencing confirms the presence of distinct core microbiota between pig breeds, with alterations in taxonomic distribution and modulations in β diversity. RP displayed a significant higher Firmicutes/Bacteroidetes ratio and apparent genera differences compared with YP. Transplanting the porcine microbiota into GF mice replicated the phenotypes of the donors. RP and their GF mouse recipients exhibited a higher body fat mass, a higher slow-contracting fiber proportion, a decreased fiber size and fast IIb fiber percentage, and enhanced lipogenesis in the gastrocnemius muscle. Furthermore, the gut microbiota composition of colonized mice shared high similarity with their donor pigs. Taken together, the gut microbiota of obese pigs intrinsically influences skeletal muscle development and the lipid metabolic profiles.

Tolerance Signatures in Transplant Recipients

PubMed Central

Newell, Kenneth A.; Turka, Laurence A.

2015-01-01

Purpose of review The intent of this review is to describe biomarkers that predict or identify individuals who exhibit tolerance to a transplanted organ. The identification of tolerance biomarkers would spare some individuals the toxicity of immunosuppressive agents, enhance the safety of studies to induce tolerance, and provide insights into mechanisms of tolerance that may aid in designing new regimens. Recent findings Studies of tolerant kidney transplant recipients have revealed an association with B cells. More recent studies have suggested that these B cells may be less mature than from those in nontolerant recipients, and specially suited to suppress alloimmune responses. Biomarkers in tolerant liver transplant patients appear to be distinct from those associated renal tolerance. Most reports have identified an association with NK and/or γδ T cells rather than B cells. Recent data indicate biomarkers associated with iron homeostasis within the transplanted liver more accurately predict the tolerant state than do biomarkers expressed in the blood, suggesting that the renal allograft itself, which is infrequently sampled, would be informative. Summary Given the encouraging progress in identifying tolerance biomarkers, it will be important to validate these markers in larger studies of transplant recipients undergoing prospective minimization or withdrawal of immunosuppression. PMID:26107969

Variation in the vitreoretinal configuration of Stage 4 retinopathy of prematurity in photocoagulated and treatment naive eyes undergoing vitrectomy

PubMed Central

Gadkari, Salil Sharad; Deshpande, Madan

2017-01-01

Purpose: We sought to document the difference in the vitreoretinal configuration of Stage 4 retinopathy of prematurity (ROP) in photocoagulated and treatment naive eyes undergoing vitrectomy and to correlate it with surgical complexity. Methods: Consecutive eyes posted for vitrectomy with Stage 4 ROP were documented preoperatively using a RetCam for the presence of peripheral traction (PT), presence of central traction just outside the arcades, and presence of traction extending to the lens. A note was made of the following intraoperative events: lensectomy, intraoperative bleeding, and iatrogenic breaks. Wilcoxon rank-sum test was used for analysis. Results: From a total of 46 eyes, 16 and 30 eyes were from the treated and treatment naive group, respectively. More eyes in the treated group had central (P < 0.0001) and lenticular traction (P = 0.022). More eyes in the untreated group had PT (P < 0.0001). A significant number of eyes without photocoagulation needed lensectomy (P = 0.042), and no difference in intraoperative bleeding (P = 0.94) was demonstrable. Iatrogenic retinotomy occurred in three eyes, all naive. Notably, age at surgery was more in the untreated group (P = 0.00008). Conclusion: Vasoproliferative activity in all retinopathies occurs at the junction of the ischemic and nonischemic retina. In the natural course of ROP, this takes place peripherally, at the ridge. In photocoagulated eyes, this junction is displaced posteriorly due to peripheral ablation. Treated eyes manifested with posterior proliferative changes and were more amenable to lens-sparing vitrectomy. Naive eyes were older when they underwent surgery to relieve PT with greater chances of lensectomy and iatrogenic breaks. PMID:28905829

Outcomes of Early Adolescent Donor Hearts in Adult Transplant Recipients.

PubMed

Madan, Shivank; Patel, Snehal R; Vlismas, Peter; Saeed, Omar; Murthy, Sandhya; Forest, Stephen; Jakobleff, William; Sims, Daniel; Lamour, Jacqueline M; Hsu, Daphne T; Shin, Julia; Goldstein, Daniel; Jorde, Ulrich P

2017-12-01

This study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts. Despite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established. All adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics. Of the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07). In this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Impact of the Data Collection on Adverse Events of Anti-HIV Drugs cohort study on abacavir prescription among treatment-naive, HIV-infected patients in Canada.

PubMed

Antoniou, Tony; Gillis, Jennifer; Loutfy, Mona R; Cooper, Curtis; Hogg, Robert S; Klein, Marina B; Machouf, Nima; Montaner, Julio S G; Rourke, Sean B; Tsoukas, Chris; Raboud, Janet M

2014-01-01

To evaluate the trends in abacavir (ABC) prescription among antiretroviral (ARV) medication-naive individuals following the presentation of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) cohort study. We conducted a retrospective cohort study of ARV medication-naive individuals in the Canadian Observational Cohort (CANOC). Between January 1, 2000, and February 28, 2010, a total of 7280 ARV medication-naive patients were included in CANOC. We observed a significant change in the proportion of new ABC prescriptions immediately following the release of DAD (-11%; 95% confidence interval [CI]: -20% to -2.4%) and in the months following the presentation of these data (-0.66% per month; 95% CI: -1.2% to -0.073%). A post-DAD presentation decrease in the odds of being prescribed ABC versus tenofovir (TDF) was observed (adjusted odds ratio, 0.72 per year, 95% CI: 0.54-0.97). Presentation of the DAD was associated with a significant decrease in ABC use among ARV medication-naive, HIV-positive patients initiating therapy.

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

PubMed

Akiyama, K; Tsuchida, K; Kanzaki, A; Ujike, H; Hamamura, T; Kondo, K; Mutoh, S; Miyanagi, K; Kuroda, S; Otsuki, S

1995-11-15

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Infusion of mesenchymal stem cells protects lung transplants from cold ischemia-reperfusion injury in mice.

PubMed

Tian, Weijun; Liu, Yi; Zhang, Bai; Dai, Xiangchen; Li, Guang; Li, Xiaochun; Zhang, Zhixiang; Du, Caigan; Wang, Hao

2015-02-01

Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation. Donor lungs from C57BL/6 mice were exposed to 6 h of cold ischemia before transplanted to syngeneic recipients. MSCs were isolated from the bone marrows of C57BL/6 mice for recipient treatment. Gas exchange was determined by the measurement of blood oxygenation, and lung injury and inflammation were assessed by histological analyses. Intravenously delivered MSC migration/trafficking to the lung grafts occurred within 4-hours post-transplantation. As compared to untreated controls, the graft arterial blood oxygenation (PaO2/FiO2) capacity was significantly improved in MSC-treated recipients as early as 4 h post-reperfusion and such improvement continued over time. By 72 h, oxygenation reached normal level that was not seen in controls. MSCs treatment conferred significant protection of the grafts from cold IRI and cell apoptosis, which is correlated with less cellular infiltration, a decrease in proinflammatory cytokines (TNF-α, IL-6) and toll-like receptor 4, and an increase in anti-inflammatory TSG-6 generation. MSCs provide significant protection against cold IRI in lung transplants, and thus may be a promising strategy to improve outcomes after lung transplantation.

Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

PubMed

Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

2016-05-01

Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

Immunization of Aged Mice with a Pneumococcal Conjugate Vaccine Combined with an Unmethylated CpG-Containing Oligodeoxynucleotide Restores Defective Immunoglobulin G Antipolysaccharide Responses and Specific CD4+-T-Cell Priming to Young Adult Levels

DTIC Science & Technology

2006-04-01

aged and young adult mice made comparable levels of proinflammatory cytokines in response to CpG-ODN, although cells from aged mice secreted higher...sepsis, is significantly elevated in the elderly relative to young adults (37, 60). Defective innate immunity including diminished neutrophil and...young adult recipients (15). Exposure to inflammatory cy- tokines in vivo could restore the defective CD4-T-cell function in aged mice (20). Pn

Is Children's Naive Knowledge Consistent?: A Comparison of the Concepts of Sound and Heat

ERIC Educational Resources Information Center

Lautrey, Jacques; Mazens, Karine

2004-01-01

The aim of this study was to shed some light on the organization of naive knowledge, and on the process of conceptual change in everyday physics, more specifically regarding the concepts of sound and heat. Eighty-three 8-year-old children were interviewed individually in order to see if they attributed the properties of objects (such as…

Exposure of FVIII in the Presence of Phosphatidyl Serine Reduces Generation of Memory B-Cells and Induces Regulatory T-Cell-Mediated Hyporesponsiveness in Hemophilia A Mice.

PubMed

Ramakrishnan, Radha; Davidowitz, Andrew; Balu-Iyer, Sathy V

2015-08-01

A major complication of replacement therapy with Factor VIII (FVIII) for hemophilia A (HA) is the development of unwanted immune responses. Previous studies showed that administration of FVIII in the presence of phosphatidyl serine (PS) reduced the development of anti-FVIII antibodies in HA mice. However, the impact of PS-mediated effects on immunological memory, such as generation of memory B-cells, is not clear. The effect of PS on memory B-cells was therefore investigated using adoptive transfer approach in FVIII(-/-) HA mice. Adoptive transfer of memory B-cells from a PS-FVIII-treated group to naïve mice followed by challenge of the recipient mice with FVIII showed a significantly reduced anti-FVIII antibody response in the recipient mice, compared with animals that received memory B-cells from free FVIII and FVIII-charge matched phosphatidyl glycerol (PG) group. The decrease in memory B-cell response is accompanied by an increase in FoxP3 expressing regulatory T-cells (Tregs). Flow cytometry studies showed that the generation of Tregs is higher in PS-treated animals as compared with FVIII and FVIII-PG treated animals. The PS-mediated hyporesponsiveness was found to be antigen-specific. The PS-FVIII immunization showed hyporesponsiveness toward FVIII rechallenge but not against ovalbumin (OVA) rechallenge, an unrelated antigen. This demonstrates that PS reduces immunologic memory of FVIII and induces antigen-specific peripheral tolerance in HA mice. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

The reproducibility of adenosine monophosphate bronchial challenges in mild, steroid-naive asthmatics

PubMed Central

Singh, Dave; Fairwood, Jennifer; Murdoch, Robert; Weeks, Amanda; Russell, Paul; Roy, Kay; Langley, Steve; Woodcock, Ashley

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Repeated adenosine monophosphate (AMP) challenges are used to assess drug effects in asthma clinical trials, but may be prone to tachyphylaxis when repeated at short intervals. Possible tachyphylaxis at 12- and 24-h intervals has not been studied. WHAT THIS STUDY ADDS Clinically relevant tachyphylaxis after repeated AMP challenges does not occur when repeated at 12- and 24-h intervals. AMP challenges at these intervals can be used to assess drug effects in clinical trials. AIMS Repeated adenosine monophosphate (AMP) challenges are used to assess drug efficacy in clinical trials of mild, steroid-naive asthmatics. Refractoriness has been reported after repeated challenges over short intervals. This study evaluated possible tachyphylaxis after repeated AMP challenges at 12 and 24 h in mild, steroid-naive asthmatics. METHODS This was an open, three-way crossover study. Twenty-six steroid-naive asthmatic subjects were randomized to the following AMP challenge regimens separated by 7–14 days: (A) challenge at 08.00 h, repeated 24 h later; (B) challenge at 08.00 h, repeated 12 and 24 h later; (C) challenge at 20.00 h, repeated 12 h later. Comparisons within day were assessed using 90% confidence intervals (CIs). Non-inferiority approach taken with 1 doubling concentration (DC) as a clinically relevant difference. RESULTS Regimen A: Significant increase in AMP reactivity at 24 h. Mean DC difference was 0.6 (90% CI 0.24, 0.96). Regimen B: No evidence of difference between AMP reactivity at 08.00 h and a repeated challenge 12 h later. Repeated challenge at 24 h caused a significant increase in provocation concentration (PC)20 compared with 12 h (mean DC difference 0.48, 90% CI 0.02, 0.95) and 0 h (mean DC difference 0.82, 90% CI 0.49, 1.14 – the upper CI exceeds the criteria of 1 DC). Challenge regimen C: No difference between challenges; mean DC difference of 0.28 (90% CI −0.2, 0.76). CONCLUSION The small decline in AMP

Perceptions of donors and recipients regarding blood donation.

PubMed

Conceição, Vander Monteiro da; Araújo, Jeferson Santos; Oliveira, Rafaela Azevedo Abrantes de; Santana, Mary Elizabeth de; Zago, Márcia Maria Fontão

2016-01-01

The aim of this study was to identify the perceptions of blood donors and recipients regarding the act of donating blood. This descriptive study with a survey design focuses on subjective and cultural aspects. Twenty donors and 20 recipients in the blood bank at the time of data collection participated in the study. Interviews were analyzed according to deductive thematic analysis. Two themes emerged - perceptions of donors and perceptions of recipients. Both groups saw the act of donating blood as something positive, though donors associated their reports with the experiences of people close to them who needed blood transfusions, while the recipients associated donations with the maintenance of their lives as, for them, a blood transfusion was a necessary medical treatment. Perceptions regarding blood donations are culturally constructed, as the participants associated knowledge acquired in the social world with moral issues and their life experiences. Hence, in addition to helping others, these individuals feel socially and morally rewarded. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Cost of lifetime immunosuppression coverage for kidney transplant recipients.

PubMed

Page, Timothy F; Woodward, Robert S

2008-01-01

On January 1, 2000, Medicare extended the coverage of immunosuppression medications from 3 years to life for elderly and disabled kidney transplant recipients. This research estimates the impact of extending this lifetime coverage to all kidney transplant recipients on Medicare's cash flows. The study finds that extending coverage to all kidney transplant recipients would have increased Medicare's net cash outflows if the coverage were extended for patients of all income levels. There is evidence that extending coverage to only patients in the lowest income quartile could have resulted in a net cost savings to Medicare.

Experience of dolutegravir in HIV-infected treatment-naive patients from a tertiary care University Hospital in Ireland

PubMed Central

Waqas, Sarmad; O’Connor, Mairead; Levey, Ciara; Mallon, Paddy; Sheehan, Gerard; Patel, Anjali; Avramovic, Gordana; Lambert, John S

2016-01-01

Objective: Dolutegravir, an HIV integrase inhibitor, is a relatively new treatment option. To assess the tolerability, side effects, and time to viral decline to non-detectable in patients newly started on dolutegravir. Methods: Retrospective health care record of 61 consecutive HIV treatment-naive patients started on dolutegravir was reviewed and analysed on SPSS. Results: The mean initial viral load was 160826.05 copies/mL (range, 79–1,126,617 copies/mL). HIV viral load became non-detectable in 63.9% of patients on dolutegravir within 3 months. In all, 60.7% of patients reported no side effects on dolutegravir; 98.4% of the patients claimed full compliance to their antiretrovirals. Conclusion: Dolutegravir was found to be efficacious and well tolerated in HIV-infected treatment-naive patients. PMID:27826447

24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

Code of Federal Regulations, 2014 CFR

2014-04-01

... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

Code of Federal Regulations, 2013 CFR

2013-04-01

... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

Code of Federal Regulations, 2012 CFR

2012-04-01

... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

Code of Federal Regulations, 2011 CFR

2011-04-01

... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

Code of Federal Regulations, 2010 CFR

2010-04-01

... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

20 CFR 627.423 - Funding restrictions for “high-risk” recipients and subrecipients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... recipient or subrecipient may be considered “high-risk” if an awarding agency determines that the recipient... such funding restrictions, the awarding official will notify the recipient or subrecipient as early as... recipients and subrecipients. 627.423 Section 627.423 Employees' Benefits EMPLOYMENT AND TRAINING...

20 CFR 627.423 - Funding restrictions for “high-risk” recipients and subrecipients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... recipient or subrecipient may be considered “high-risk” if an awarding agency determines that the recipient... such funding restrictions, the awarding official will notify the recipient or subrecipient as early as... recipients and subrecipients. 627.423 Section 627.423 Employees' Benefits EMPLOYMENT AND TRAINING...

20 CFR 627.423 - Funding restrictions for “high-risk” recipients and subrecipients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... recipient or subrecipient may be considered “high-risk” if an awarding agency determines that the recipient... such funding restrictions, the awarding official will notify the recipient or subrecipient as early as... recipients and subrecipients. 627.423 Section 627.423 Employees' Benefits EMPLOYMENT AND TRAINING...

Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

NASA Astrophysics Data System (ADS)

Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

1983-01-01

A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

PubMed

Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

2017-10-01

Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the

13 CFR 305.7 - Services performed by the Recipient's own forces.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Recipient's own forces. 305.7 Section 305.7 Business Credit and Assistance ECONOMIC DEVELOPMENT... Approved Projects § 305.7 Services performed by the Recipient's own forces. In certain circumstances, the... employed by the Recipient either full-time or part-time. EDA may approve the use of such “in-house forces...

Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.

PubMed

Han, Xiaoning; Chen, Michael; Wang, Fushun; Windrem, Martha; Wang, Su; Shanz, Steven; Xu, Qiwu; Oberheim, Nancy Ann; Bekar, Lane; Betstadt, Sarah; Silva, Alcino J; Takano, Takahiro; Goldman, Steven A; Nedergaard, Maiken

2013-03-07

Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice

PubMed Central

Han, Xiaoning; Chen, Michael; Wang, Fushun; Windrem, Martha; Wang, Su; Shanz, Steven; Xu, Qiwu; Oberheim, Nancy Ann; Bekar, Lane; Betstadt, Sarah; Silva, Alcino J.; Takano, Takahiro; Goldman, Steven A.; Nedergaard, Maiken

2013-01-01

Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice. PMID:23472873

Deletion of Fanca or Fancd2 dysregulates Treg in mice

PubMed Central

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

2014-01-01

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

Deletion of Fanca or Fancd2 dysregulates Treg in mice.

PubMed

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

2014-03-20

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

High fat diet drives obesity regardless the composition of gut microbiota in mice

PubMed Central

Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L.; Chou, Chieh Jason

2016-01-01

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1st week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice. PMID:27577172

High fat diet drives obesity regardless the composition of gut microbiota in mice.

PubMed

Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L; Chou, Chieh Jason

2016-08-31

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.

Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats

PubMed Central

Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T.; Mummalaneni, Shobha; Melone, Pamela; Ren, ZuoJun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S.; Katsumata, Tadayoshi; DeSimone, John A.

2011-01-01

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5–40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure. PMID:21849614

Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats.

PubMed

Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Ren, Zuojun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S; Katsumata, Tadayoshi; DeSimone, John A; Lyall, Vijay

2011-11-01

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure.

Recipient design in human communication: simple heuristics or perspective taking?

PubMed

Blokpoel, Mark; van Kesteren, Marlieke; Stolk, Arjen; Haselager, Pim; Toni, Ivan; van Rooij, Iris

2012-01-01

Humans have a remarkable capacity for tuning their communicative behaviors to different addressees, a phenomenon also known as recipient design. It remains unclear how this tuning of communicative behavior is implemented during live human interactions. Classical theories of communication postulate that recipient design involves perspective taking, i.e., the communicator selects her behavior based on her hypotheses about beliefs and knowledge of the recipient. More recently, researchers have argued that perspective taking is computationally too costly to be a plausible mechanism in everyday human communication. These researchers propose that computationally simple mechanisms, or heuristics, are exploited to perform recipient design. Such heuristics may be able to adapt communicative behavior to an addressee with no consideration for the addressee's beliefs and knowledge. To test whether the simpler of the two mechanisms is sufficient for explaining the "how" of recipient design we studied communicators' behaviors in the context of a non-verbal communicative task (the Tacit Communication Game, TCG). We found that the specificity of the observed trial-by-trial adjustments made by communicators is parsimoniously explained by perspective taking, but not by simple heuristics. This finding is important as it suggests that humans do have a computationally efficient way of taking beliefs and knowledge of a recipient into account.

Recipient design in human communication: simple heuristics or perspective taking?

PubMed Central

Blokpoel, Mark; van Kesteren, Marlieke; Stolk, Arjen; Haselager, Pim; Toni, Ivan; van Rooij, Iris

2012-01-01

Humans have a remarkable capacity for tuning their communicative behaviors to different addressees, a phenomenon also known as recipient design. It remains unclear how this tuning of communicative behavior is implemented during live human interactions. Classical theories of communication postulate that recipient design involves perspective taking, i.e., the communicator selects her behavior based on her hypotheses about beliefs and knowledge of the recipient. More recently, researchers have argued that perspective taking is computationally too costly to be a plausible mechanism in everyday human communication. These researchers propose that computationally simple mechanisms, or heuristics, are exploited to perform recipient design. Such heuristics may be able to adapt communicative behavior to an addressee with no consideration for the addressee's beliefs and knowledge. To test whether the simpler of the two mechanisms is sufficient for explaining the “how” of recipient design we studied communicators' behaviors in the context of a non-verbal communicative task (the Tacit Communication Game, TCG). We found that the specificity of the observed trial-by-trial adjustments made by communicators is parsimoniously explained by perspective taking, but not by simple heuristics. This finding is important as it suggests that humans do have a computationally efficient way of taking beliefs and knowledge of a recipient into account. PMID:23055960

32 CFR 37.850 - Should I require recipients to mark data?

Code of Federal Regulations, 2013 CFR

2013-07-01

... from disclosure with a legend identifying the data as licensed data subject to use, release, or... 32 National Defense 1 2013-07-01 2013-07-01 false Should I require recipients to mark data? 37.850... Intellectual Property § 37.850 Should I require recipients to mark data? To protect the recipient's interests...

32 CFR 37.850 - Should I require recipients to mark data?

Code of Federal Regulations, 2012 CFR

2012-07-01

... from disclosure with a legend identifying the data as licensed data subject to use, release, or... 32 National Defense 1 2012-07-01 2012-07-01 false Should I require recipients to mark data? 37.850... Intellectual Property § 37.850 Should I require recipients to mark data? To protect the recipient's interests...

42 CFR 456.604 - Physician team member inspecting care of recipients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Physician team member inspecting care of recipients... Intermediate Care Facilities and Institutions for Mental Diseases § 456.604 Physician team member inspecting care of recipients. No physician member of a team may inspect the care of a recipient for whom he is...

42 CFR 456.604 - Physician team member inspecting care of recipients.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Physician team member inspecting care of recipients... Intermediate Care Facilities and Institutions for Mental Diseases § 456.604 Physician team member inspecting care of recipients. No physician member of a team may inspect the care of a recipient for whom he is...

Clean Air Excellence Award Recipients

EPA Pesticide Factsheets

Recipients are organized by award category within each year: Clean Air Technology, Community Action, Education/Outreach, Regulatory/Policy Innovations, Transportation Efficiency Innovations, Thomas W. Zosel individual, and Gregg Cooke Visionary Program.

Regulatory CD8+CD122+ T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells

PubMed Central

Lapato, Andrew; Vandenbark, Arthur A.; Murphy, Stephanie J.; Saugstad, Julie A.; Offner, Halina

2014-01-01

Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that transfer of IL-10+ B-cells reduced infarct volume in male C57BL/6J (wild-type, WT) recipient mice when given 24 h prior to or 4 h after middle cerebral artery occlusion (MCAO). The purpose of this study was to determine if passively transferred IL-10+ B-cells can exert therapeutic and immunoregulatory effects when injected 24 hours after MCAO induction in B-cell-sufficient male WT mice. The results demonstrated that IL-10+ B-cell treated mice had significantly reduced infarct volumes in the ipsilateral cortex and hemisphere and improved neurological deficits vs. Vehicle-treated control mice after 60 min occlusion and 96 h of reperfusion. The MCAO-protected B-cell recipient mice had less splenic atrophy and reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres compared with Vehicle-treated control mice. These immunoregulatory changes occurred in concert with the predominant appearance of IL-10-secreting CD8+CD122+ Treg cells in both the spleen and the MCAO-affected brain hemisphere. This study for the first time demonstrates a major neuroprotective role for IL-10+ B-cells in treating MCAO in male WT mice at a time point well beyond the ~4 h tPA treatment window, leading to the generation of a dominant IL-10+CD8+CD122+ Treg population associated with spleen preservation and reduced CNS inflammation. PMID:25537181

Unusual presentations of BK virus infections in pediatric renal transplant recipients.

PubMed

Drake, Keri A; Najera, Lydia; Reed, Robyn C; Verghese, Priya S

2013-02-01

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients. © 2012 John Wiley & Sons A/S.

Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces specific immune responses in mice

PubMed Central

Weigand, Kilian; Voigt, Franziska; Encke, Jens; Hoyler, Birgit; Stremmel, Wolfgang; Eisenbach, Christoph

2012-01-01

AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole “viral surface” induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cells directed against HCV. Furthermore, T-cell responses confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further. PMID:22371638

Profiles of blood and blood component transfusion recipients in Zimbabwe

PubMed Central

Mafirakureva, Nyashadzaishe; Khoza, Star; Hassall, Oliver; Faragher, Brian E.; Kajja, Isaac; Mvere, David A.; Emmanuel, Jean C.; Postma, Maarten J.; van Hulst, Marinus

2015-01-01

Background There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Materials and methods Data on the characteristics of the blood transfusion recipients (age, sex, blood group), blood components received (type, quantity), discharge diagnoses and outcomes following transfusion (discharge status, duration of stay in hospital), were retrospectively collected from four major hospitals for the period from January 1, 2012 to December 31, 2012. Diagnoses were grouped into broad categories according to the disease headings of the International Classification of Diseases (ICD-10). Surgical procedures were grouped into broad categories according to organ system using ICD-9. Results Most of the 1,793 transfusion recipients studied were female (63.2%) and in the reproductive age group, i.e. 15–49 years (65.3%). The median age of the recipients was 33 years (range, 0–93). The majority of these recipients (n=1,642; 91.6%) received a red blood cell transfusion. The majority of the patients were diagnosed with conditions related to pregnancy and childbirth (22.3%), and diseases of blood and blood-forming organs (17.7%). The median time spent in hospital was 8 days (range, 0–214) and in-hospital mortality was 15.4%. Discussion Our sample of blood transfusion recipients were fairly young and most of them received red blood cell transfusions. The majority of patients in the reproductive age group received blood transfusions for pregnancy and childbirth-related diagnoses. PMID:26192782

Linking Welfare Recipients to Jobs: The Role of Temporary Help Agencies.

ERIC Educational Resources Information Center

Bugarin, Alicia

Successful welfare reform requires quickly moving welfare recipients into jobs. Components to this challenge include the following: a poor fit between where jobs are located and where many welfare recipients live; recipients who lack experience and skills and do not know how to seek, find, or qualify for jobs; childcare and transportation needs;…

Risk Factors for Melanoma in Renal Transplant Recipients.

PubMed

Ascha, Mona; Ascha, Mustafa S; Tanenbaum, Joseph; Bordeaux, Jeremy S

2017-11-01

Melanoma risk factors and incidence in renal transplant recipients can inform decision making for both patients and clinicians. To determine risk factors and characteristics of renal transplant recipients who develop melanoma. This cohort study of a large national data registry used a cohort of renal transplant recipients from the United States Renal Data System (USRDS) database from the years 2004 through 2012. Differences in baseline characteristics between those who did and did not develop melanoma were examined, and a survival analysis was performed. Patients with renal transplants who received a diagnosis of melanoma according to any inpatient or outpatient claim associated with a billing code for melanoma were included. A history of pretransplant melanoma, previous kidney transplantation, or transplantation after 2012 or before 2004 were exclusion criteria. The data analysis was conducted from 2015 to 2016. Receipt of a renal transplant. Incidence and risk factors for melanoma. Of 105 174 patients (64 151 [60.7%] male; mean [SD] age, 49.6 [15.3] years) who received kidney transplants between 2004 and 2012, 488 (0.4%) had a record of melanoma after transplantation. Significant risk factors for developing melanoma vs not developing melanoma included older age among recipients (mean [SD] age, 60.5 [10.2] vs 49.7 [15.3] years; P < .001) and donors (42.6 [15.0] vs 39.2 [15.1] years; P < .001), male sex (71.5% vs 60.7%; P < .001), recipient (96.1% vs 66.5%; P < .001) and donor (92.4% vs 82.9%; P < .001) white race, less than 4 HLA mismatches (44.9% vs 37.1%; P = .001), living donors (44.7% vs 33.7%; P < .001), and sirolimus (22.3% vs 13.2%; P < .001) and cyclosporine (4.9% vs 3.2%; P = .04) therapy. Risk factors significant on survival analysis included older recipient age (hazard ratio [HR] per year, 1.06; 95% CI, 1.05-1.06; P < .001), recipient male sex (HR, 1.53; 95% CI, 1.25-1.88; P < .001), recipient white race

Matching donor to recipient in liver transplantation: Relevance in clinical practice

PubMed Central

Reddy, Mettu Srinivas; Varghese, Joy; Venkataraman, Jayanthi; Rela, Mohamed

2013-01-01

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’ clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down. PMID:24303088

Global Symmetries of Naive and Staggered Fermions in Arbitrary Dimensions

NASA Astrophysics Data System (ADS)

Kieburg, Mario; Würfel, Tim R.

2018-03-01

It is well-known that staggered fermions do not necessarily satisfy the same global symmetries as the continuum theory. We analyze the mechanism behind this phenomenon for arbitrary dimension and gauge group representation. For this purpose we vary the number of lattice sites between even and odd parity in each single direction. Since the global symmetries are manifest in the lowest eigenvalues of the Dirac operator, the spectral statistics and also the symmetry breaking pattern will be affected. We analyze these effects and compare our predictions with Monte-Carlo simulations of naive Dirac operators in the strong coupling limit. This proceeding is a summary of our work [1].

Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A

PubMed Central

Vallejo, Abbe N.; Michel, Joshua J.; Bale, Laurie K.; Lemster, Bonnie H.; Borghesi, Lisa; Conover, Cheryl A.

2009-01-01

Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). Homozygous deletion of PAPPA in mice leads to lifespan extension. Since immune function is an important determinant of individual fitness, we examined the natural immune ecology of PAPPA−/− mice and their wild-type littermates reared under specific pathogen-free condition with aging. Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA−/− mice maintain discrete thymic cortex and medulla densely populated by CD4+CD8+ thymocytes that are capable of differentiating into single-positive CD4 and CD8 T cells. Old PAPPA−/− mice have high levels of T cell receptor excision circles, and have bone marrows enriched for subsets of thymus-seeding progenitors. PAPPA−/− mice have an overall larger pool of naive T cells, and also exhibit an age-dependent accumulation of CD44+CD43+ memory T cells similar to wild-type mice. However, CD43+ T cell subsets of old PAPPA−/− mice have significantly lower prevalence of 1B11 and S7, glycosylation isoforms known to inhibit T cell activation with normal aging. In bioassays of cell activation, splenic T cells of old PAPPA−/− mice have high levels of activation antigens and cytokine production, and also elicit Ig production by autologous B cells at levels equivalent to young wild-type mice. These data suggest an IGF-immune axis of healthy longevity. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune homeostasis during postnatal development and aging. PMID:19549878

28 CFR 42.722 - Recipient assessment of age distinctions.

Code of Federal Regulations, 2014 CFR

2014-07-01