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Sample records for il-15 confer sterile

  1. Sterilization: A Conference and a Report.

    ERIC Educational Resources Information Center

    Dillingham, Brint

    1978-01-01

    This article continues a series on Native American sterilization, based on a conference of the National Council of Churches' Interreligious Foundation for Community Organization (IFCO). Also included are an article and a report by the American Civil Liberties Union. (Author/RTS)

  2. An activation-induced IL-15 isoform is a natural antagonist for IL-15 function

    PubMed Central

    Zhao, Lei; Hu, Bo; Zhang, Yinsheng; Song, Yuan; Lin, Dandan; Liu, Yonghao; Mei, Yu; Sandikin, Dedy; Sun, Weiping; Zhuang, Min; Liu, Haiyan

    2016-01-01

    Interleukin 15 (IL-15) expression induces the secretion of inflammatory cytokines, inhibits the apoptosis of activated T cells and prolongs the survival of CD8+ memory T cells. Here we identified an IL-15 isoform lacking exon-6, IL-15ΔE6, generated by alternative splicing events of activated immune cells, including macrophages and B cells. In vitro study showed that IL-15ΔE6 could antagonize IL-15-mediated T cell proliferation. The receptor binding assay revealed that IL-15ΔE6 could bind to IL-15Rα and interfere with the binding between IL-15 and IL-15Rα. Over-expression of IL-15ΔE6 in the murine EAE model ameliorated the EAE symptoms of the mice. The clinical scores were significantly lower in the mice expressing IL-15ΔE6 than the control mice and the mice expressing IL-15. The inflammation and demyelination of the EAE mice expressing IL-15ΔE6 were less severe than the control group. Furthermore, flow cytometry analysis demonstrated that IL-15ΔE6 expression reduced the percentages of inflammatory T cells in the spleen and spinal cord, and inhibited the infiltration of macrophages to the CNS. Our results demonstrated that IL-15ΔE6 could be induced during immune activation and function as a negative feedback mechanism to dampen IL-15-mediated inflammatory events. PMID:27166125

  3. Characterization of interleukin-15 (IL-15) and the IL-15 receptor complex

    SciTech Connect

    Kennedy, M.K.; Park, L.S.

    1996-05-01

    IL-15 interacts with a heterotrimeric receptor that consists of the {beta} and {gamma} subunits of the IL-2 receptor (IL-2R) as well as a specific, high-affinity IL-15-binding subunit, which is designated IL-15R{alpha}. Since both the {beta} and the {gamma} subunits of the IL-2R are required for signaling by either IL-2 or IL-15, it is not surprising that these cytokines share many activities in vitro. However, the differential expression of these cytokines and the {alpha} chains of their receptors within various tissues and cell types suggests that IL-2 and IL-15 may perform at least partially distinct physiological functions. The production of IL-15 by macrophages, and possibly other cell types, in response to environmental stimuli and infectious agents suggests that IL-15 may play a role in protective immune responses, allograft rejection, and the pathogenesis of autoimmune diseases. 56 refs.

  4. Higher constitutive IL15Rα expression and lower IL-15 response threshold in coeliac disease patients

    PubMed Central

    Bernardo, D; Garrote, J A; Allegretti, Y; León, A; Gómez, E; Bermejo-Martin, J F; Calvo, C; Riestra, S; Fernández-Salazar, L; Blanco-Quirós, A; Chirdo, F; Arranz, E

    2008-01-01

    The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15Rα mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15Rα mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0·0334, on GCD P = 0·0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15Rα expression was only triggered in non-CD controls (P = 0·0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFNγ (P = 0·0313, P = 0·0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine. PMID:18821940

  5. From Anabolic to Oxidative: Reconsidering the Roles of IL-15 and IL-15Rα in Skeletal Muscle

    PubMed Central

    Pistilli, Emidio E.; Quinn, LeBris S.

    2016-01-01

    Interleukin-15 (IL-15) and its receptor, IL-15 receptor-alpha (IL-15Rα), are suggested to function in determination of skeletal muscle phenotypes, with IL-15 originally proposed as an anabolic cytokine. This review will focus on recent work demonstrating that manipulation of IL-15 and IL-15Rα in vivo promotes changes in exercise capacity, muscle fatigue, and gene expression indicative of a more oxidative skeletal muscle phenotype. PMID:23072822

  6. Homeostasis of IL-15 dependent lymphocyte subsets in the liver

    PubMed Central

    Cepero-Donates, Yuneivy; Rakotoarivelo, Volatiana; Mayhue, Marian; Ma, Averil; Chen, Yi-Guang; Ramanathan, Sheela

    2017-01-01

    IL-15 is a member of the gamma chain family of cytokines (γc – CD132). The IL-15 receptor (IL-15R) complex consists of 3 subunits: the ligand-binding IL-15Rα chain (CD215), the β chain (CD122; also used by IL-2), and the common γ chain. The biological activities of IL-15 are mostly mediated by the IL-15:IL-15Rα complex, produced by the same cell and ‘trans-presented’ to responder cells expressing the IL-15Rβγc. The peculiar and almost unique requirement for IL-15 to be trans-presented by IL-15Rα suggests that the biological effects of IL-15 signaling are tightly regulated even at the level of availability of IL-15. Tissue-specific deletion of IL-15Rα has shown macrophage-and dendritic cell-derived IL-15Rα mediate the homeostasis of different CD8+ T cell subsets. Here we show that hepatocyte and macrophage- specific expression of IL-15Rα is required to maintain the homeostasis of NK and NKT cells in the liver. Thus, homeostasis of IL-15-dependent lymphocyte subsets is also regulated by trans-presentation of IL-15 by non-hematopoietic cells in the tissue environment. PMID:26778709

  7. Sterilization.

    PubMed

    Peterson, Herbert B

    2008-01-01

    Worldwide, sterilization (tubal sterilization and vasectomy) is used by more people than any other method of contraception. All techniques of tubal sterilization in widespread use in the United States have low risks of surgical complications. Although tubal sterilization is highly effective, the risk of pregnancy varies by age and method of occlusion. Pregnancies can occur many years after the procedure, and when they do, the risk of ectopic gestation is high. There is now strong evidence against the existence of a post-tubal ligation syndrome of menstrual abnormalities. Although women who have undergone tubal sterilization are more likely than other women to undergo hysterectomy subsequently, there is no known biologic basis for this relationship. Although sterilization is intended to be permanent, expressions of regret and requests for reversal are not uncommon and are much more likely to occur among women sterilized at young ages. Tubal sterilization has little or no effect on sexual function for most women. Vasectomy is less likely than tubal sterilization to result in serious complications. Minor complications, however, are not uncommon. Vasectomy does not increase the risk of heart disease, and available evidence argues against an increase in the risk of prostate cancer, testicular cancer, or overall mortality. Whether a postvasectomy pain syndrome exists remains controversial. Although the long-term effectiveness of vasectomy is less well-studied than that for tubal sterilization, it seems likely to be at least as effective. Intrauterine devices and progestin implants are long-acting, highly effective alternatives to sterilization.

  8. IL-15/IL-15 receptor biology: a guided tour through an expanding universe.

    PubMed

    Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

    2006-08-01

    The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.

  9. Soluble Interleukin IL-15Ralpha is generated by alternative splicing or proteolytic cleavage and forms functional complexes with IL-15.

    PubMed

    Bulanova, Elena; Budagian, Vadim; Duitman, Erwin; Orinska, Zane; Krause, Hans; Rückert, Rene; Reiling, Norbert; Bulfone-Paus, Silvia

    2007-05-04

    Interleukin 15 (IL-15) is a pleiotropic cytokine that is hardly detectable in biological fluids. Here, we show that IL-15 forms functional heterocomplexes with soluble high affinity IL-15 receptor alpha (IL-15Ralpha) chain in mouse serum and cell-conditioned medium, which prevents IL-15 detection by ELISA. We also demonstrate that two soluble IL-15Ralpha (sIL-15Ralpha) sushi domain isoforms are generated through a novel alternative splicing mechanism within the IL-15Ralpha gene. These isoforms potentiate IL-15 action by promoting the IL-15-mediated proliferation of the CTLL cell line and interferon gamma production by murine NK cells, which suggests a role in IL-15 transpresentation. Conversely, a full-length sIL-15Ralpha ectodomain released by tumor necrosis factor-alpha-converting enzyme (TACE)-dependent proteolysis inhibits IL-15 activity. Thus, a dual mechanism of sIL-15Ralpha generation exists in mice, giving rise to polypeptides with distinct properties, which regulate IL-15 function.

  10. Mast cells express novel functional IL-15 receptor alpha isoforms.

    PubMed

    Bulanova, Elena; Budagian, Vadim; Orinska, Zane; Krause, Hans; Paus, Ralf; Bulfone-Paus, Silvia

    2003-05-15

    Mast cells previously have been reported to be regulated by IL-15 and to express a distinct IL-15R, termed IL-15RX. To further examine IL-15 binding and signaling in mast cells, we have studied the nature of the IL-15R and some of its biological activities in these cells. In this study, we report the existence of three novel isoforms of the IL-15R alpha chain in murine bone marrow-derived mast cells as a result of an alternative exon-splicing mechanism within the IL-15R alpha gene. These correspond to new mRNA transcripts lacking exon 4; exons 3 and 4; or exons 3, 4, and 5 (IL-15R alpha Delta 4, IL-15R alpha Delta 3,4, IL-15R alpha Delta 3,4,5). After transient transfection in COS-7 cells, all IL-15R alpha isoforms associate with the Golgi apparatus, the endoplasmic reticulum, the perinuclear space, and the cell membrane. Analysis of glycosylation pattern demonstrates the usage of a single N-glycosylation site, while no O-glycosylation is observed. Importantly, IL-15 binds with high affinity to, and promotes the survival of, murine BA/F3 cells stably transfected with the IL-15R alpha isoforms. Furthermore, we report that signaling mediated by IL-15 binding to the newly identified IL-15R alpha isoforms involves the phosphorylation of STAT3, STAT5, STAT6, Janus kinase 2, and Syk kinase. Taken together, our data indicate that murine mast cells express novel, fully functional IL-15R alpha isoforms, which can explain the selective regulatory effects of IL-15 on these cells.

  11. Sterilization.

    PubMed

    Rioux, M H

    1979-05-01

    The history of sterilization in North America has included enactment of laws in 37 U. S. states and 2 Canadian provinces allowing the procedure to be performed to eliminate undesirable, genetically-transmitted traits. These eugenic laws applied to any of the following categories of persons: mentally regarded, mentally ill, epileptic, criminal, alcoholic, or poor people. Pressure from geneticists, lawyers, and others concerned with the implications of such laws, led to their repeal in many places. Noneugenic and nontherapeutic sterilization is today a recognized medical practice. Legally, such procedures must meet the following criteria: 1) informed consent; 2) individual benefit; and 3) performance with reasonable care and skill. If these criteria are met, doctors are protected from legal liability. The most legal, social, and ethical ambiguities arise in cases where nontherapeutic sterilization is performed on individuals unable to give consent, e.g., minors or mentally handicapped persons.

  12. Autocrine role of vascular IL-15 in intimal thickening

    SciTech Connect

    Cercek, Miha . E-mail: DimayugaP@cshs.org

    2006-01-13

    Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor {alpha} expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling.

  13. IRF-1 promotes liver transplant ischemia/reperfusion injury via hepatocyte IL-15/IL-15Rα production

    PubMed Central

    Yokota, Shinichiro; Yoshida, Osamu; Dou, Lei; Spadaro, Anthony V.; Isse, Kumiko; Ross, Mark A.; Stolz, Donna B.; Kimura, Shoko; Du, Qiang; Demetris, Anthony J.; Thomson, Angus W.; Geller, David A.

    2015-01-01

    Ischemia and reperfusion (I/R) injury following liver transplantation (LTx) is an important problem that significantly impacts clinical outcomes. Interferon regulatory factor-1 (IRF-1) is a nuclear transcription factor that plays a critical role in liver injury. Our objective was to determine the immunomodulatory role of IRF-1 during I/R injury following allogeneic LTx. IRF-1 was induced in liver grafts immediately after reperfusion in both human and mouse LTx. IRF-1 contributed significantly to I/R injury as IRF-1 KO grafts displayed much less damage assessed by serum alanine aminotransferase (ALT) and histology. In vitro, IRF-1 regulated both constitutive and induced expression of IL-15, as well as IL-15Rα mRNA expression in murine hepatocytes and liver dendritic cells (DC). Specific knockdown of IRF-1 in human primary hepatocytes gave similar results. In addition, we identified hepatocytes as the major producer of soluble IL-15/IL-15Rα complexes in the liver. IRF-1 KO livers had significantly reduced NK, NKT and CD8+T cell numbers, while rIL-15/IL-15Rα restored these immune cells, augmented cytotoxic effector molecules, promoted systemic inflammatory responses, and exacerbated liver injury in IRF-1 KO graft recipients. These results indicate that IRF-1 promotes LTx I/R injury via hepatocyte IL-15/IL-15Rα production and suggest that targeting IRF-1 and IL-15/IL-15Rα may be effective in reducing I/R injury associated with LTx. PMID:25964490

  14. IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells.

    PubMed

    Schenkel, Jason M; Fraser, Kathryn A; Casey, Kerry A; Beura, Lalit K; Pauken, Kristen E; Vezys, Vaiva; Masopust, David

    2016-05-01

    IL-15 regulates central and effector memory CD8 T cell (TCM and TEM, respectively) homeostatic proliferation, maintenance, and longevity. Consequently, IL-15 availability hypothetically defines the carrying capacity for total memory CD8 T cells within the host. In conflict with this hypothesis, previous observations demonstrated that boosting generates preternaturally abundant TEM that increases the total quantity of memory CD8 T cells in mice. In this article, we provide a potential mechanistic explanation by reporting that boosted circulating TEM do not require IL-15 for maintenance. We also investigated tissue-resident memory CD8 T cells (TRM), which protect nonlymphoid tissues from reinfection. We observed up to a 50-fold increase in the total magnitude of TRM in mouse mucosal tissues after boosting, suggesting that the memory T cell capacity in tissues is flexible and that TRM may not be under the same homeostatic regulation as primary central memory CD8 T cells and TEM Further analysis identified distinct TRM populations that depended on IL-15 for homeostatic proliferation and survival, depended on IL-15 for homeostatic proliferation but not for survival, or did not depend on IL-15 for either process. These observations on the numerical regulation of T cell memory indicate that there may be significant heterogeneity among distinct TRM populations and also argue against the common perception that developing vaccines that confer protection by establishing abundant TEM and TRM will necessarily erode immunity to previously encountered pathogens as the result of competition for IL-15. Copyright © 2016 by The American Association of Immunologists, Inc.

  15. IL-15/sIL-15Rα gene transfer suppresses Lewis lung cancer growth in the lungs, liver and kidneys.

    PubMed

    Sun, H; Liu, D

    2016-01-01

    Nearly 40% of people with lung cancer have tumor growth in other organs at the time of diagnosis. Current treatment strategies for patients with late-stage lung cancer are primarily palliative and only showed modest efficacy. The current study takes advantage of the hydrodynamic gene delivery technique to evaluate the antitumor activity of interleukin (IL)-15/sIL-15Rα on lung tumors growing in the lungs, liver and kidneys. We demonstrate that hydrodynamic tail vein injection of 2 μg of AG209 DP muIL-15sRα+IL-15 plasmid resulted in serum IL-15/sIL-15Rα reaching a peak level of ~10 μg ml(-1) 1 day after the injection and gradually declined to ~5 ng ml(-1) within 3 days. Quantitative PCR analysis revealed that overexpression of IL-15/sIL-15Rα induced the activation of natural killer and T cells, evidenced by increased mRNA levels of marker genes including granzyme B, perforin, Ifn-γ, T-bet and Cd8 in the lungs, liver and kidneys. Importantly, transfer of the Il-15/sIl-15Rα gene alone, or in combination with gemcitabine chemotherapy, significantly inhibited the tumor growth in these three organs and prolonged median survival time of treated mice by 1.7- and 3.3-fold, respectively. The therapeutic benefits are principally blockade and elimination of tumor growth in the liver and kidneys. Taken together, these results suggest that IL-15/sIL-15Rα-based gene therapy could be an effective approach to treat late-stage lung cancer with metastases in other organs.

  16. IL-15: a central regulator of celiac disease immunopathology

    PubMed Central

    Abadie, Valérie; Jabri, Bana

    2014-01-01

    Summary Interleukin-15 (IL-15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL-15 upregulation has been reported in many organ-specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL-15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL-15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL-15 with regards to the main immunological processes involved in the pathogenesis of celiac disease. PMID:24942692

  17. Transcriptional IL-15-Directed in vivo DC Targeting DNA Vaccine

    PubMed Central

    Tian, S; Liu, Z; Donahue, C; Noh, HS; Falo, LD; You, Z

    2009-01-01

    DC engineered in vitro by DNA encoding OVAhsp70 and IL-15 up-regulated their expressions of CD80, CD86, CCR7 and IL-15Rα and promoted their productions of IL-6, IL-12 and TNF-α. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine encoding OVAhsp70 elicited long-lasting Th1 and CTL responses and anti-B16OVA activity. CD8 T cell-mediated primary tumor protection was abrogated by DC or CD4 T cell depletion during the induction phase of immune responses. However, CD4 T cell depletion during immunization did not impair CD8 T cell-dependent long-lasting tumor protection. Furthermore, in vivo DC-derived IL-15 exerted the enhancements of cellular and humoral immune responses and antitumor immunity elicited by OVAhsp70 DNA vaccine. Importantly, the potency of this novel DNA vaccine strategy was proven using a self/tumor Ag (TRP2) in a clinically relevant B16 melanoma model. These findings have implications for developing next generation DNA vaccines against cancers and infectious diseases in both healthy and CD4 deficient individuals. PMID:19727134

  18. Transpresentation of interleukin-15 by IL-15/IL-15Rα mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity

    PubMed Central

    Van den Bergh, Johan; Willemen, Yannick; Lion, Eva; Van Acker, Heleen; De Reu, Hans; Anguille, Sébastien; Goossens, Herman; Berneman, Zwi

    2015-01-01

    In cancer immunotherapy, the use of dendritic cell (DC)-based vaccination strategies can improve overall survival, but until now durable clinical responses remain scarce. To date, DC vaccines are designed primarily to induce effective T-cell responses, ignoring the antitumor activity potential of natural killer (NK) cells. Aiming to further improve current DC vaccination outcome, we engineered monocyte-derived DC to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Rα) using mRNA electroporation. The addition of IL-15Rα to the protocol, enabling IL-15 transpresentation to neighboring NK cells, resulted in significantly better NK-cell activation compared to IL-15 alone. Next to upregulation of NK-cell membrane activation markers, IL-15 transpresentation resulted in increased NK-cell secretion of IFN-γ, granzyme B and perforin. Moreover, IL-15-transpresenting DC/NK cell cocultures from both healthy donors and acute myeloid leukemia (AML) patients in remission showed markedly enhanced cytotoxic activity against NK cell sensitive and resistant tumor cells. Blocking IL-15 transpresentation abrogated NK cell-mediated cytotoxicity against tumor cells, pointing to a pivotal role of IL-15 transpresentation by IL-15Rα to exert its NK cell-activating effects. In conclusion, we report an attractive approach to improve antitumoral NK-cell activity in DC-based vaccine strategies through the use of IL-15/IL-15Rα mRNA-engineered designer DC. PMID:26675759

  19. How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor α▿

    PubMed Central

    Duitman, Erwin H.; Orinska, Zane; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

    2008-01-01

    While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor α (IL-15Rα). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15Rα and then is secreted. This intracellular IL-15/IL-15Rα complex already is formed in the endoplasmic reticulum and, thus, enables the further trafficking of complexed IL-15 through the secretory pathway. Just transfecting IL-15Rα in cells, which transcribe but normally do not secrete IL-15, suffices to induce IL-15 secretion. Thus, we provide the first evidence of how a cytokine is chaperoned through the secretory pathway by complexing with its own high-affinity receptor and show that IL-15/IL-15Rα offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion. PMID:18505820

  20. How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor: lessons from interleukin-15 (IL-15)/IL-15 receptor alpha.

    PubMed

    Duitman, Erwin H; Orinska, Zane; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

    2008-08-01

    While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor alpha (IL-15R alpha). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15R alpha and then is secreted. This intracellular IL-15/IL-15R alpha complex already is formed in the endoplasmic reticulum and, thus, enables the further trafficking of complexed IL-15 through the secretory pathway. Just transfecting IL-15R alpha in cells, which transcribe but normally do not secrete IL-15, suffices to induce IL-15 secretion. Thus, we provide the first evidence of how a cytokine is chaperoned through the secretory pathway by complexing with its own high-affinity receptor and show that IL-15/IL-15R alpha offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion.

  1. Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses.

    PubMed

    Rückert, René; Brandt, Katja; Bulanova, Elena; Mirghomizadeh, Farhad; Paus, Ralf; Bulfone-Paus, Silvia

    2003-12-01

    The development and the differentiation of CD8(+) T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8(+) T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15(-/-)) mice or mice treated with soluble IL-15Ralpha as an IL-15 antagonist showed significantly reduced CD8(+) T cell-dependent DTH responses, while activation of CD4(+) T cell and B cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) from IL-15(+/+), IL-15(-/-) or IL-15Ralpha(-/-) mice revealed that DC-derived IL-15 is an absolute requirement for the initiation of DTH response. The re-establishment of the interaction of IL-15 with the IL-15Ralpha by incubating IL-15(-/-) DC with IL-15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of pro-inflammatory cytokines by DC and triggered in vitro CD8(+) T cell proliferation and IL-2 release. Taken together, the data suggest that an autocrine IL-15/IL-15Ralpha signaling loop in DC is essential for inducing CD8(+)-dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeutic modulation of clinically relevant DTH reactions.

  2. IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis.

    PubMed

    Pierce, Joseph R; Maples, Jill M; Hickner, Robert C

    2015-06-15

    Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m(2); n = 10) and obese (BMI: 34.7 ± 3.5 kg/m(2); n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown.

  3. LigB subunit vaccine confers sterile immunity against challenge in the hamster model of leptospirosis

    PubMed Central

    Silveira, Marcelle M.; Félix, Samuel; Mendonça, Karla S.; Santos, Cleiton S.; Athanazio, Daniel A.; Medeiros, Marco A.; Reis, Mitermayer G.

    2017-01-01

    Neglected tropical diseases, including zoonoses such as leptospirosis, have a major impact on rural and poor urban communities, particularly in developing countries. This has led to major investment in antipoverty vaccines that focus on diseases that influence public health and thereby productivity. While the true, global, impact of leptospirosis is unknown due to the lack of adequate laboratory diagnosis, the WHO estimates that incidence has doubled over the last 15 years to over 1 million cases that require hospitalization every year. Leptospirosis is caused by pathogenic Leptospira spp. and is spread through direct contact with infected animals, their urine or contaminated water and soil. Inactivated leptospirosis vaccines, or bacterins, are approved in only a handful of countries due to the lack of heterologous protection (there are > 250 pathogenic Leptospira serovars) and the serious side-effects associated with vaccination. Currently, research has focused on recombinant vaccines, a possible solution to these problems. However, due to a lack of standardised animal models, rigorous statistical analysis and poor reproducibility, this approach has met with limited success. We evaluated a subunit vaccine preparation, based on a conserved region of the leptospiral immunoglobulin-like B protein (LigB(131–645)) and aluminium hydroxide (AH), in the hamster model of leptospirosis. The vaccine conferred significant protection (80.0–100%, P < 0.05) against mortality in vaccinated animals in seven independent experiments. The efficacy of the LigB(131–645)/AH vaccine ranged from 87.5–100% and we observed sterile immunity (87.5–100%) among the vaccinated survivors. Significant levels of IgM and IgG were induced among vaccinated animals, although they did not correlate with immunity. A mixed IgG1/IgG2 subclass profile was associated with the subunit vaccine, compared to the predominant IgG2 profile seen in bacterin vaccinated hamsters. These findings suggest that

  4. LigB subunit vaccine confers sterile immunity against challenge in the hamster model of leptospirosis.

    PubMed

    Conrad, Neida L; Cruz McBride, Flávia W; Souza, Jéssica D; Silveira, Marcelle M; Félix, Samuel; Mendonça, Karla S; Santos, Cleiton S; Athanazio, Daniel A; Medeiros, Marco A; Reis, Mitermayer G; Dellagostin, Odir A; McBride, Alan J A

    2017-03-01

    Neglected tropical diseases, including zoonoses such as leptospirosis, have a major impact on rural and poor urban communities, particularly in developing countries. This has led to major investment in antipoverty vaccines that focus on diseases that influence public health and thereby productivity. While the true, global, impact of leptospirosis is unknown due to the lack of adequate laboratory diagnosis, the WHO estimates that incidence has doubled over the last 15 years to over 1 million cases that require hospitalization every year. Leptospirosis is caused by pathogenic Leptospira spp. and is spread through direct contact with infected animals, their urine or contaminated water and soil. Inactivated leptospirosis vaccines, or bacterins, are approved in only a handful of countries due to the lack of heterologous protection (there are > 250 pathogenic Leptospira serovars) and the serious side-effects associated with vaccination. Currently, research has focused on recombinant vaccines, a possible solution to these problems. However, due to a lack of standardised animal models, rigorous statistical analysis and poor reproducibility, this approach has met with limited success. We evaluated a subunit vaccine preparation, based on a conserved region of the leptospiral immunoglobulin-like B protein (LigB(131-645)) and aluminium hydroxide (AH), in the hamster model of leptospirosis. The vaccine conferred significant protection (80.0-100%, P < 0.05) against mortality in vaccinated animals in seven independent experiments. The efficacy of the LigB(131-645)/AH vaccine ranged from 87.5-100% and we observed sterile immunity (87.5-100%) among the vaccinated survivors. Significant levels of IgM and IgG were induced among vaccinated animals, although they did not correlate with immunity. A mixed IgG1/IgG2 subclass profile was associated with the subunit vaccine, compared to the predominant IgG2 profile seen in bacterin vaccinated hamsters. These findings suggest that LigB(131

  5. The IL-15R alpha chain signals through association with Syk in human B cells.

    PubMed

    Bulanova, E; Budagian, V; Pohl, T; Krause, H; Dürkop, H; Paus, R; Bulfone-Paus, S

    2001-12-01

    The alpha-chain of the IL-15R (IL-15Ralpha) serves as the specific, high-affinity receptor for IL-15. It is expressed by lymphoid and nonlymphoid cells, including B cell lymphoma lines. In this study, we have further explored IL-15Ralpha-mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15Ralpha and IL-2Rgamma chains, but lacks the IL-2Rbeta chain. Stimulation of Raji cells with IL-15 induces their proliferation and rescues them from C2-ceramide-induced apoptosis. By immunoprecipitation and Western blotting, we show that treatment of Raji cells and activated primary B cells with IL-15 induces coprecipitation of Syk kinase with the IL-15Ralpha chain. Upon association, the activated Syk kinase phosphorylates the IL-15Ralpha chain as well as phospholipase Cgamma, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15Ralpha and phospholipase Cgamma phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells.

  6. Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain.

    PubMed

    Bulfone-Paus, S; Bulanova, E; Pohl, T; Budagian, V; Durkop, H; Ruckert, R; Kunzendorf, U; Paus, R; Krause, H

    1999-09-01

    Interleukin-15 (IL-15) is a potent inhibitor of several apoptosis pathways. One prominent path toward apoptosis is the ligand-induced association of TNF receptor 1 (TNFR1) with death domain adaptor proteins. Studying if and how IL-15 blocks TNFR1-mediated apoptosis in a murine fibroblast cell line (L929), we show here that IL-15 blocks TNFR1-induced apoptosis via IL-15Ralpha chain signaling. The intracellular tail of IL-15Ralpha shows sequence homologies to the TRAF2 binding motifs of CD30 and CD40. Most important, binding of IL-15 to IL-15Ralpha successfully competes with the TNFR1 complex for TRAF2 binding, which may impede assembly of key adaptor proteins to the TNFR1 complex, and induces IkappaBalpha phosphorylation. Thus, IL-15Ralpha chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-alpha and IL-15 surface as major opponents in apoptosis control.

  7. A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control

    PubMed Central

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Thon, Lutz; Mamat, Uwe; Bellosta, Paola; Basilico, Claudio; Adam, Dieter; Paus, Ralf; Bulfone-Paus, Silvia

    2005-01-01

    Discrimination between cytokine receptor and receptor tyrosine kinase (RTK) signaling pathways is a central paradigm in signal transduction research. Here, we report a ‘promiscuous liaison' between both receptors that enables interleukin (IL)-15 to transactivate the signaling pathway of a tyrosine kinase. IL-15 protects murine L929 fibroblasts from tumor necrosis factor α (TNFα)-induced cell death, but fails to rescue them upon targeted depletion of the RTK, Axl; however, Axl-overexpressing fibroblasts are TNFα-resistant. IL-15Rα and Axl colocalize on the cell membrane and co-immunoprecipitate even in the absence of IL-15, whereby the extracellular part of Axl proved to be essential for Axl/IL-15Rα interaction. Most strikingly, IL-15 treatment mimics stimulation by the Axl ligand, Gas6, resulting in a rapid tyrosine phosphorylation of both Axl and IL-15Rα, and activation of the phosphatidylinositol 3-kinase/Akt pathway. This is also seen in mouse embryonic fibroblasts from wild-type but not Axl−/− or IL-15Rα−/− mice. Thus, IL-15-induced protection from TNFα-mediated cell death involves a hitherto unknown IL-15 receptor complex, consisting of IL-15Rα and Axl RTK, and requires their reciprocal activation initiated by ligand-induced IL-15Rα. PMID:16308569

  8. A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control.

    PubMed

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Thon, Lutz; Mamat, Uwe; Bellosta, Paola; Basilico, Claudio; Adam, Dieter; Paus, Ralf; Bulfone-Paus, Silvia

    2005-12-21

    Discrimination between cytokine receptor and receptor tyrosine kinase (RTK) signaling pathways is a central paradigm in signal transduction research. Here, we report a 'promiscuous liaison' between both receptors that enables interleukin (IL)-15 to transactivate the signaling pathway of a tyrosine kinase. IL-15 protects murine L929 fibroblasts from tumor necrosis factor alpha (TNFalpha)-induced cell death, but fails to rescue them upon targeted depletion of the RTK, Axl; however, Axl-overexpressing fibroblasts are TNFalpha-resistant. IL-15Ralpha and Axl colocalize on the cell membrane and co-immunoprecipitate even in the absence of IL-15, whereby the extracellular part of Axl proved to be essential for Axl/IL-15Ralpha interaction. Most strikingly, IL-15 treatment mimics stimulation by the Axl ligand, Gas6, resulting in a rapid tyrosine phosphorylation of both Axl and IL-15Ralpha, and activation of the phosphatidylinositol 3-kinase/Akt pathway. This is also seen in mouse embryonic fibroblasts from wild-type but not Axl-/- or IL-15Ralpha-/- mice. Thus, IL-15-induced protection from TNFalpha-mediated cell death involves a hitherto unknown IL-15 receptor complex, consisting of IL-15Ralpha and Axl RTK, and requires their reciprocal activation initiated by ligand-induced IL-15Ralpha.

  9. IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis

    PubMed Central

    Pierce, Joseph R.; Maples, Jill M.

    2015-01-01

    Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m2; n = 10) and obese (BMI: 34.7 ± 3.5 kg/m2; n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown. PMID:25921578

  10. hIL-15 gene-modified human natural killer cells (NKL-IL15) augments the anti-human hepatocellular carcinoma effect in vivo.

    PubMed

    Jiang, Wen; Zhang, Cai; Tian, Zhigang; Zhang, Jian

    2014-07-01

    Genetic modification of NK cells may provide new possibilities for developing effective cancer immunotherapy by improving NK cell function and specificity. We previously established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their therapeutic efficiency against human hepatocellular carcinoma (HCC) in vitro. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy, we further investigated their natural cytotoxicity against HCC in vivo in the present study. NKL-IL15 cells exhibited strong inhibition on the growth of transplanted human HCC tumors in xenograft nude mouse models. Further investigation showed that NKL-IL15 cells expressed much higher levels of cytolysis-related molecules, including NKp80, TRAIL, granzyme B, IFN-γ, and TNF-α, than parental NKL cells in response to HCC stimulation. Moreover, soluble mediators secreted by NKL-IL15 cells decreased HCC cell proliferation; in particular, NKL-IL15-derived TNF-α and IFN-γ induced higher NKG2D ligand expression on target cells and resulted in the increased susceptibility of HCCs to NKL-mediated cytolysis. These results show that hIL-15 gene-modified human NK cells can augment the anti-tumor effect of NK cells on human HCC in vivo and suggest their promising applicability as a new candidate for adoptive immunotherapy against HCCs in the future. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. IL-15 Expression on RA Synovial Fibroblasts Promotes B Cell Survival

    PubMed Central

    Benito-Miguel, Marta; García-Carmona, Yolanda; Balsa, Alejandro; Bautista-Caro, María-Belén; Arroyo-Villa, Irene; Cobo-Ibáñez, Tatiana; Bonilla-Hernán, María Gema; de Ayala, Carlos Pérez; Sánchez-Mateos, Paloma; Martín-Mola, Emilio; Miranda-Carús, María-Eugenia

    2012-01-01

    Introduction The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib) IL-15 expression on B cell survival. Methods Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. Results RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/−8% (p<0.001). IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/−6% (p<0.05). Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. Conclusion IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains. PMID:22792388

  12. A barley PHD finger transcription factor that confers male sterility by affecting tapetal development.

    PubMed

    Fernández Gómez, José; Wilson, Zoe A

    2014-08-01

    Controlling pollen development is of major commercial importance in generating hybrid crops and selective breeding, but characterized genes for male sterility in crops are rare, with no current examples in barley. However, translation of knowledge from model species is now providing opportunities to understand and manipulate such processes in economically important crops. We have used information from regulatory networks in Arabidopsis to identify and functionally characterize a barley PHD transcription factor MALE STERTILITY1 (MS1), which expresses in the anther tapetum and plays a critical role during pollen development. Comparative analysis of Arabidopsis, rice and Brachypodium genomes was used to identify conserved regions in MS1 for primer design to amplify the barley MS1 gene; RACE-PCR was subsequently used to generate the full-length sequence. This gene shows anther-specific tapetal expression, between late tetrad stage and early microspore release. HvMS1 silencing and overexpression in barley resulted in male sterility. Additionally, HvMS1 cDNA, controlled by the native Arabidopsis MS1 promoter, successfully complemented the homozygous ms1 Arabidopsis mutant. These results confirm the conservation of MS1 function in higher plants and in particular in temperate cereals. This has provided the first example of a characterized male sterility gene in barley, which presents a valuable tool for the future control of male fertility in barley for hybrid development.

  13. Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS.

    PubMed

    Vaknin-Dembinsky, Adi; Brass, Steven D; Brass, Steven; Gandhi, Roopali; Weiner, Howard L

    2008-03-01

    IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.

  14. Novel IL-15 isoforms generated by alternative splicing are expressed in the intestinal epithelium.

    PubMed

    Tan, X; Lefrançois, L

    2006-07-01

    Previous studies have identified mRNA three isoforms encoding interleukin-15 (IL-15) that are produced through differential splicing and encode for the same mature IL-15 protein with two different signal peptides. Our analysis of mouse intestinal epithelial cells revealed two new IL-15 mRNA isoforms generated by different alternative splicing events. In one form (IL-15DeltaE6), exon 6 is absent, and in the second form the first 48 nt of exon 7 are absent (IL-15DeltaE7) through usage of an alternative 5' splicing site within exon 7. These mRNA isoforms encoded in-frame IL-15 protein variants lacking either 15aa (IL-15DeltaE6) or 16aa (IL-15DeltaE7) both utilizing the normal long signal peptide. Significant structural changes were predicted for these new IL-15 isoforms. RNAse protection assays revealed the highest expression of isoform mRNA in the intestinal epithelium and functional analysis of recombinant IL-15 isoform proteins suggested possible regulatory functions.

  15. Interleukin-15, IL-15 Receptor-Alpha, and Obesity: Concordance of Laboratory Animal and Human Genetic Studies

    PubMed Central

    Quinn, LeBris S.; Anderson, Barbara G.

    2011-01-01

    Interleukin-15 (IL-15) is a cytokine which inhibits lipid deposition in cultured adipocytes and decreases adipose tissue deposition in laboratory rodents. In human subjects, negative correlations between circulating IL-15 levels and both total and abdominal fat have been demonstrated. Deletions of IL15 in humans and mice are associated with obesity, while gain-of-function IL-15 overexpressing mice are resistant to diet-induced obesity. IL-15 is highly (but not exclusively) expressed at the mRNA level in skeletal muscle tissue, and the regulation of IL-15 translation and secretion is complex. Conflicting evidence exists concerning whether circulating IL-15 is released from skeletal muscle tissue in response to exercise or other physiological stimuli. The IL-15 receptor-alpha (IL-15Rα) subunit has a complex biochemistry, encoding both membrane-bound and soluble forms which can modulate IL-15 secretion and bioactivity. The gene encoding this receptor, IL15RA, resides on human chromosome 10p, a location linked to obesity and type-2 diabetes. Several single-nucleotide polymorphisms (SNPs) in human IL15RA and IL15 correlate with adiposity and markers of the metabolic syndrome. Genetic variation in IL15RA may modulate IL-15 bioavailability, which in turn regulates adiposity. Thus, IL-15 and the IL-15Rα may be novel targets for pharmacologic control of obesity in the human population. PMID:21603270

  16. IL-15 complexes induce NK cell and T cell responses independent of type I IFN signalling during rhinovirus infection

    PubMed Central

    Jayaraman, Annabelle; Jackson, David J.; Message, Simon D.; Pearson, Rebecca M.; Aniscenko, Julia; Caramori, Gaetano; Mallia, Patrick; Papi, Alberto; Shamji, Betty; Edwards, Matt; Westwick, John; Hansel, Trevor; Stanciu, Luminita A.; Johnston, Sebastian L.; Bartlett, Nathan W.

    2014-01-01

    Rhinoviruses are the most common virus to infect man causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity however their function during rhinovirus infection in vivo is undefined. In RV infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expression of IL-15 and IL-15Rα which in turn were required for NK- and CD8+ T-cell responses. Treatment with IL-15-IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9 and CXCL10 followed by recruitment of activated, IFN-γ expressing NK, CD8+ and CD4+ T cells. Treating infected IFNAR1−/− mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ and CXCL9 (but not CXCL10) expression also followed by NK-, CD8+- and CD4+-T cell recruitment and activation. We have demonstrated that type I IFN induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment which in turn was sufficient to drive IFN-γ expression and lymphocyte responses. PMID:24472849

  17. Enhancement of the inhibitory effect of an IL-15 antagonist peptide by alanine scanning.

    PubMed

    Savio, Alicia Santos; Acosta, Osvaldo Reyes; Pérez, Haydee Gerónimo; Alvarez, Yunier Rodríguez; Chico, Araceli; Pérez, Hilda Garay; Ojeda, Miriam Ojeda; Aguero, Celia Aurora Arrieta; Estévez, Miguel; Nieto, Gerardo Guillen

    2012-01-01

    IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Rα and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm. We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis.

  18. An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation.

    PubMed

    Lee, Tsung-Lin; Chang, Mei-Ling; Lin, Yu-Jei; Tsai, Ming-Hsun; Chang, Yi-Hsuan; Chuang, Che-Ming; Chien, Yun; Sosinowski, Tomasz; Wang, Chih-Hsiu; Chen, Yi-Yuan; Lee, Chien-Kuo; Chen, Jau-Shiuh; Wang, Li-Fang; Kung, John T; Ku, Chia-Chi

    2015-05-01

    In a routine phenotype-driven screen, we identified a point mutation in exon 7 of the IL-15 gene in Pedigree 191 (deficient memory (DM)) of N-ethyl-N-nitrosourea mutagenized mice. The DM epidermis expressed an alternatively spliced IL-15 mRNA isoform, IL-15ΔE7, and a wild-type (WT) IL-15 isoform at comparable levels. Mechanical stimulation of DM skin or DM skin graft transplanted onto the WT host resulted in reduced keratinocyte activation and inhibition of neutrophil infiltration into the dermis, demonstrating that DM keratinocytes produced less inflammatory response to external stimulation. Ectopic expression of IL-15ΔE7 in WT skin prevented abrasion-induced epidermal thickening, blocked the accumulation of nuclear antigen Ki67(+) cells in the basal and the suprabasal cell layers, increased loricrin expression, and also increased keratinocyte CXCL1 and G-CSF production. IL-15ΔE7 also profoundly blocked neutrophil infiltration in SDS- or immiquimod (IMQ)-treated WT skin. Recombinant IL-15ΔE7 failed to activate STAT-5 and its downstream target bcl-2 expression. Our study points to IL-15ΔE7 as a potential therapeutic agent for treating neutrophilia-associated inflammatory skin disorders.

  19. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model.

    PubMed

    Villadsen, Louise S; Schuurman, Janine; Beurskens, Frank; Dam, Tomas N; Dagnaes-Hansen, Frederik; Skov, Lone; Rygaard, Jorgen; Voorhorst-Ogink, Marleen M; Gerritsen, Arnout F; van Dijk, Marc A; Parren, Paul W H I; Baadsgaard, Ole; van de Winkel, Jan G J

    2003-11-01

    Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels. One of these cytokines, IL-15, triggers inflammatory cell recruitment, angiogenesis, and production of other inflammatory cytokines, including IFN-gamma, TNF-alpha, and IL-17, which are all upregulated in psoriatic lesions. To investigate the role of IL-15 in psoriasis, we generated mAb's using human immunoglobulin-transgenic mice. One of the IL-15-specific antibodies we generated, 146B7, did not compete with IL-15 for binding to its receptor but potently interfered with the assembly of the IL-15 receptor alpha, beta, gamma complex. This antibody effectively blocked IL-15-induced T cell proliferation and monocyte TNF-alpha release in vitro. In a human psoriasis xenograft model, antibody 146B7 reduced the severity of psoriasis, as measured by epidermal thickness, grade of parakeratosis, and numbers of inflammatory cells and cycling keratinocytes. These results obtained with this IL-15-specific mAb support an important role for IL-15 in the pathogenesis of psoriasis.

  20. IL-15Rα deficiency leads to mitochondrial and myofiber differences in fast mouse muscles.

    PubMed

    Pistilli, Emidio E; Guo, Ge; Stauber, William T

    2013-01-01

    The purpose of this study was to determine mitochondrial changes in fast muscles from interleukin-15 receptor alpha knockout (IL-15RαKO) mice. We tested the hypothesis that fast muscles from IL-15RαKO mice would have a greater mitochondrial density and altered internal structure compared to muscles from control mice. In fast muscles from IL-15RαKO mice, mitochondrial density was 48% greater with a corresponding increase in mitochondrial DNA content. Although there were no differences in the relative size of isolated mitochondria, internal complexity was lower in mitochondria from IL-15RαKO mice. These data support an increase in mitochondrial biogenesis and provide direct evidence for a greater density and altered internal structure of mitochondria in EDL muscles deficient in IL-15Rα.

  1. IL-15Rα deficiency leads to mitochondrial and myofiber differences in fast mouse muscles

    PubMed Central

    Pistilli, Emidio E.; Guo, Ge; Stauber, William T.

    2016-01-01

    The purpose of this study was to determine mitochondrial changes in fast muscles from interleukin-15 receptor alpha knockout (IL-15RαKO) mice. We tested the hypothesis that fast muscles from IL-15RαKO mice would have a greater mitochondrial density and altered internal structure compared to muscles from control mice. In fast muscles from IL-15RαKO mice, mitochondrial density was 48% greater with a corresponding increase in mitochondrial DNA content. Although there were no differences in the relative size of isolated mitochondria, internal complexity was lower in mitochondria from IL-15RαKO mice. These data support an increase in mitochondrial biogenesis and provide direct evidence for a greater density and altered internal structure of mitochondria in EDL muscles deficient in IL-15Rα. PMID:23116661

  2. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

    PubMed

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G; Muenzer, Jared T; Ferguson, Thomas A; Chang, Katherine; Osborne, Dale F; Clark, Andrew T; Coopersmith, Craig M; McDunn, Jonathan E; Hotchkiss, Richard S

    2010-02-01

    IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.

  3. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation.

    PubMed

    Stonier, Spencer W; Ma, Lisa J; Castillo, Eliseo F; Schluns, Kimberly S

    2008-12-01

    Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Ralpha(+) DCs through the preferential enhancement of a subset of KLRG-1(+)CD27(-) CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis.

  4. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation

    PubMed Central

    Stonier, Spencer W.; Ma, Lisa J.; Castillo, Eliseo F.

    2008-01-01

    Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Rα+ DCs through the preferential enhancement of a subset of KLRG-1+CD27− CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis. PMID:18812469

  5. Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions.

    PubMed

    Ullrich, Evelyn; Bonmort, Mathieu; Mignot, Gregoire; Jacobs, Benedikt; Bosisio, Daniela; Sozzani, Silvano; Jalil, Abdelali; Louache, Fawzia; Bulanova, Elena; Geissman, Frederic; Ryffel, Bernard; Chaput, Nathalie; Bulfone-Paus, Silvia; Zitvogel, Laurence

    2008-06-15

    IFN-producing killer dendritic cells (IKDC) were initially described as B220(+)CD11c(+)CD3(-)NK1.1(+) tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Ralpha allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220(-)NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I- or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Ralpha allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.

  6. High-resolution fine mapping of ps-2, a mutated gene conferring functional male sterility in tomato due to non-dehiscent anthers.

    PubMed

    Gorguet, Benoit; Schipper, Danny; van Heusden, Adriaan W; Lindhout, Pim

    2006-11-01

    Functional male sterility is an important trait for the production of hybrid seeds. Among the genes coding for functional male sterility in tomato is the positional sterility gene ps-2. ps-2 is monogenic recessive, confers non-dehiscent anthers and is the most suitable for practical uses. In order to have tools for molecular-assisted selection (MAS) we fine mapped the ps-2 locus. This was done in an F(2) segregating population derived from the interspecific cross between a functionally male sterile line (ps-2/ps-2; Solanum lycopersicum) and a functionally male fertile line (S. pimpinellifolium). Here we report the procedure that has led to the high-resolution fine mapping of the ps-2 locus in a 1.65 cM interval delimited by markers T0958 and T0635 on the short arm of Chromosome 4. The presence of many COS markers in the local high-resolution map allowed us to study the synteny between tomato and Arabidopsis at the ps-2 locus region. No obvious candidate gene for ps-2 was identified among the known functional male sterility genes in Arabidopsis.

  7. Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles.

    PubMed

    Pistilli, Emidio E; Bogdanovich, Sasha; Garton, Fleur; Yang, Nan; Gulbin, Jason P; Conner, Jennifer D; Anderson, Barbara G; Quinn, LeBris S; North, Kathryn; Ahima, Rexford S; Khurana, Tejvir S

    2011-08-01

    IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα-knockout (IL-15Rα-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15Rα has a role in defining the phenotype of fast skeletal muscles in vivo.

  8. Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles

    PubMed Central

    Pistilli, Emidio E.; Bogdanovich, Sasha; Garton, Fleur; Yang, Nan; Gulbin, Jason P.; Conner, Jennifer D.; Anderson, Barbara G.; Quinn, LeBris S.; North, Kathryn; Ahima, Rexford S.; Khurana, Tejvir S.

    2011-01-01

    IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα–knockout (IL-15Rα–KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15Rα has a role in defining the phenotype of fast skeletal muscles in vivo. PMID:21765213

  9. Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice.

    PubMed

    Quinn, LeBris S; Anderson, Barbara G; Conner, Jennifer D; Wolden-Hanson, Tami

    2015-11-01

    Interleukin-15 (IL-15) and irisin are exercise-induced myokines that exert favorable effects on energy expenditure and metabolism. IL-15 can induce PGC-1α expression, which in turn induces expression of irisin and its precursor, FNDC5. Therefore, the present study tested the hypothesis that increases in circulating irisin levels and muscle FNDC5 mRNA expression are dependent on IL-15. Circulating irisin levels and gastrocnemius muscle FNDC5 mRNA expression were examined following acute exercise in control and IL-15-deleted (IL-15 KO) mice, following injection of IL-15 into IL-15 KO mice, and in transgenic mice with elevated circulating IL-15 levels (IL-15 Tg mice). Circulating IL-15 levels and muscle PGC-1α and PPARδ mRNA expressions were determined as positive controls. No effect of IL-15 deletion on post-exercise serum irisin levels or muscle FNDC5 mRNA expression was detected. While serum IL-15 levels and muscle PGC-1α expression were elevated post-exercise in control mice, both serum irisin levels and muscle FNDC5 expression decreased shortly after exercise in both control and IL-15 KO mice. A single injection of recombinant IL-15 into IL-15 KO mice that significantly increased muscle PPARδ and PGC-1α mRNA expressions had no effect on circulating irisin release, but modestly induced muscle FNDC5 expression. Additionally, serum irisin and gastrocnemius muscle FNDC5 expression in IL-15 Tg mice were similar to those of control mice. Muscle FNDC5 mRNA expression and irisin release are not IL-15-dependent in mice.

  10. IL-15 temporally reorients IL-10 biased B-1a cells toward IL-12 expression.

    PubMed

    Kanti Ghosh, Amlan; Sinha, Debolina; Mukherjee, Subhadeep; Biswas, Ratna; Biswas, Tapas

    2016-03-01

    Interleukin (IL)-15 is known to strongly modulate T-cell function; however, its role in controlling mucosal immunity, including its ability to modulate B-1a cell activity, remains to be elucidated. Here, we show that IL-15 upregulates activation molecules and the costimulatory molecule CD80 on viable B-1a cells. Cell activation was accompanied by the depletion of sialic acid-binding immunoglobulin-like lectin (Siglec)-G, an inhibitor of cell activation that is present on B-1a cells. The IL-15 receptor CD122 was stimulated on B-1a cells by the cytokine showing its direct involvement in IL-15-mediated responses. IL-10 is responsible for the long term survival of B-1a cells in culture, which is initially promoted by IL-15. The upregulation of IL-10 was followed by the appearance of suppressor of cytokine signaling (SOCS)1 in the presence of IL-15 and the loss of IL-10. This resulted in the cells switching to IL-12 expression. This anti-inflammatory to pro-inflammatory shift in the B-1a cell character was independent of the cell-specific marker CD5, which remained highly expressed throughout the in vitro life of the cells. The presence of the immunosuppressive receptor programmed cell death (PD)-1 and its ligand PD-L2 were features of a predominantly IL-10 response. PD-1 and PD-L2 can mediate juxtacrine signaling. However, the abrogation of PD-1 and its ligand was observed when the cells expressed IL-12. This demonstrates an inverse relationship between the receptor and ligand and the pro-inflammatory cytokine. The induction of IgM and IgA, which can play pivotal roles in mucosal immunity, was promoted in the presence of IL-15. Collectively, the data implicate IL-15 as the master cytokine that induces B-1a cells to mount a mucosal immune response.

  11. IL-15 amplifies the pathogenic properties of CD4+CD28- T cells in multiple sclerosis.

    PubMed

    Broux, Bieke; Mizee, Mark R; Vanheusden, Marjan; van der Pol, Susanne; van Horssen, Jack; Van Wijmeersch, Bart; Somers, Veerle; de Vries, Helga E; Stinissen, Piet; Hellings, Niels

    2015-03-01

    CD4(+)CD28(-) T cells arise through repeated antigenic stimulation and are present in diseased tissues of patients with various autoimmune disorders, including multiple sclerosis (MS). These cells are believed to have cytotoxic properties that contribute to the pathogenic damaging of the target organ. Endogenous cues that are increased in the diseased tissue may amplify the activity of CD4(+)CD28(-) T cells. In this study, we focused on IL-15, a cytotoxicity-promoting cytokine that is increased in the serum and cerebrospinal fluid of MS patients. Using immunohistochemistry, we demonstrate that IL-15 is mainly produced by astrocytes and infiltrating macrophages in inflammatory lesions of MS patients. Moreover, in vitro transmigration studies reveal that IL-15 selectively attracts CD4(+)CD28(-) T cells of MS patients, but not of healthy individuals. IL-15 further induces the expression of chemokine receptors and adhesion molecules on CD4(+)CD28(-) T cells, as investigated using flow cytometry, resulting in enhanced migration over a monolayer of human brain endothelial cells. Finally, flow cytometric analyses revealed that IL-15 increases the proliferation and production of GM-CSF, expression of cytotoxic molecules (NKG2D, perforin, and granzyme B), and degranulation capacity of CD4(+)CD28(-) T cells. Taken together, these findings indicate that increased peripheral and local levels of IL-15 amplify the pathogenic potential of CD4(+)CD28(-) T cells, thus contributing to tissue damage in MS brain lesions. Copyright © 2015 by The American Association of Immunologists, Inc.

  12. IL-15 expression increased in response to treadmill running and inhibited endoplasmic reticulum stress in skeletal muscle in rats.

    PubMed

    Yang, Hong-Tao; Luo, Li-Jie; Chen, Wen-Jia; Zhao, Lei; Tang, Chao-Shu; Qi, Yong-Fen; Zhang, Jing

    2015-02-01

    Interleukin 15 (IL-15) has recently been proposed as a circulating myokine involved in glucose uptake and utilization in skeletal muscle. However, the role and mechanism of IL-15 in exercise improving insulin resistance (IR) is unclear. Here, we investigated the alteration in expression of IL-15 and IL-15 receptor α (IL-15Rα) in skeletal muscle during treadmill running in rats with IR induced by a high-fat diet (HFD) and elucidated the mechanism of the anti-IR effects of IL-15. At 20 weeks of HFD, rats showed severe IR, with increased levels of fasting blood sugar and plasma insulin, impaired glucose tolerance, and reduced glucose transport activity. IL-15 immunoreactivity and mRNA level in gastrocnemius muscle were decreased markedly as compared with controls. IL-15Rα protein and mRNA levels in both soleus and gastrocnemius muscle were significantly decreased, which might attenuate the signaling or secretion of IL-15 in muscle. Eight-week treadmill running completely ameliorated HFD-induced IR and reversed the downregulated level of IL-15 and IL-15Rα in skeletal muscle of HFD-fed rats. To investigate whether IL-15 exerts its anti-IR effects directly in muscle, we pre-incubated muscle strips with the endoplasmic reticulum stress (ERS) inducer dithiothreitol (DTT) or tunicamycin (Tm); IL-15 treatment markedly decreased the protein expression of the ERS markers 78-kDa glucose-regulated protein, 94-kDa glucose-regulated protein and C/EBP homologous protein and inhibited ERS induced by DTT or Tm. Therefore, treadmill running promoted skeletal IL-15 and IL-15Rα expression in HFD-induced IR in rats. The inhibitory effect of IL-15 on ERS may be involved in improved insulin sensitivity with exercise training.

  13. Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia and Markers of Inflammation

    PubMed Central

    Swaminathan, Sanjay; Qiu, Ju; Rupert, Adam W.; Hu, Zonghui; Higgins, Jeanette; Dewar, Robin L.; Stevens, Randy; Rehm, Catherine A.; Metcalf, Julia A.; Sherman, Brad T.; Baseler, Michael W.; Lane, H. Clifford; Imamichi, Tomozumi

    2016-01-01

    Objective IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14. Design and Methods IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls). The HIV-1 infected patients were divided into 4 groups based on viral load: <50 copies/ml, 51–10,000 copies/ml, 10,001–100,000 copies/ml and >100,000 copies/ml. The Mann Whitney test (non-parametric) was used to identify significant relationships between different patient groups. Results IL-15 levels were significantly higher in patients with viral loads >100,000 copies/ml (3.02 ± 1.53 pg/ml) compared to both uninfected controls (1.69 ± 0.37 pg/ml, p<0.001) or patients with a viral load <50 copies/ml (1.59 ± 0.40 pg/ml (p<0.001). There was a significant correlation between HIV-1 viremia and IL-15 levels (Spearman r = 0.54, p<0.001) and between CD4+ T cell counts and IL-15 levels (Spearman r = -0.56, p<0.001). Conclusions IL-15 levels are significantly elevated in HIV-1 infected patients with viral loads >100,000 copies/ml compared to uninfected controls, with a significant direct correlation noted between IL-15 and HIV-1 viremia and an inverse correlation between IL-15 levels and CD4+ T cell counts. These data support a potential role for IL-15 in the pathogenesis of HIV-associated immune activation. PMID:27880829

  14. TNF Stimulates Nuclear Export and Secretion of IL-15 by Acting on CRM1 and ARF6

    PubMed Central

    Ouyang, Suidong; Hsuchou, Hung; Kastin, Abba J.; Pan, Weihong

    2013-01-01

    Interleukin (IL)-15 is a ubiquitously expressed cytokine that in the basal state is mainly localized intracellularly, including the nucleus. Unexpectedly, tumor necrosis factor-α (TNF) time-dependently induced nuclear export of IL-15Rα and IL15. This process was inhibited by leptomycine B (LMB), a specific inhibitor of nuclear export receptor chromosomal region maintenance 1 (CRM1). In the presence of TNF, LMB co-treatment led to accumulation of both IL-15Rα and IL-15 in the nucleus of HeLa cells, suggesting that CRM1 facilitates nuclear export and that TNF enhances CRM1 activity. Once in the cytoplasm, IL-15 showed partial co-localization with late endosomes but very little with other organelles tested 4 h after TNF treatment. IL-15Rα showed co-localization with both early and late endosomes, and to a lesser extent with endoplasmic reticulum and Golgi. This indicates different kinetics and possibly different trafficking routes of IL-15 from its specific receptor. The TNF-induced secretion of IL-15 was attenuated by pretreatment of cells by brefeldin A that inhibits ER-to-Golgi transport, or by use of domain negative ADP-ribosylation factor 6 (ARF6) that interferes with exocytotic sorting. We conclude that TNF abolishes nuclear localization of IL-15 and IL-15Rα by acting on CRM1, and it facilitates exocytosis of IL-15 with the involvement of ARF6. PMID:23950892

  15. TNF stimulates nuclear export and secretion of IL-15 by acting on CRM1 and ARF6.

    PubMed

    Ouyang, Suidong; Hsuchou, Hung; Kastin, Abba J; Pan, Weihong

    2013-01-01

    Interleukin (IL)-15 is a ubiquitously expressed cytokine that in the basal state is mainly localized intracellularly, including the nucleus. Unexpectedly, tumor necrosis factor-α (TNF) time-dependently induced nuclear export of IL-15Rα and IL15. This process was inhibited by leptomycine B (LMB), a specific inhibitor of nuclear export receptor chromosomal region maintenance 1 (CRM1). In the presence of TNF, LMB co-treatment led to accumulation of both IL-15Rα and IL-15 in the nucleus of HeLa cells, suggesting that CRM1 facilitates nuclear export and that TNF enhances CRM1 activity. Once in the cytoplasm, IL-15 showed partial co-localization with late endosomes but very little with other organelles tested 4 h after TNF treatment. IL-15Rα showed co-localization with both early and late endosomes, and to a lesser extent with endoplasmic reticulum and Golgi. This indicates different kinetics and possibly different trafficking routes of IL-15 from its specific receptor. The TNF-induced secretion of IL-15 was attenuated by pretreatment of cells by brefeldin A that inhibits ER-to-Golgi transport, or by use of domain negative ADP-ribosylation factor 6 (ARF6) that interferes with exocytotic sorting. We conclude that TNF abolishes nuclear localization of IL-15 and IL-15Rα by acting on CRM1, and it facilitates exocytosis of IL-15 with the involvement of ARF6.

  16. IL-15 promotes regulatory T cell function and protects against diabetes development in NK-depleted NOD mice.

    PubMed

    Xia, Jinxing; Liu, Wentao; Hu, Biliang; Tian, Zhigang; Yang, Yongguang

    2010-02-01

    IL-15, an anti-apoptotic cytokine, has been reported to promote the survival and function of NK cells and T cells, including regulatory T cells (Tregs). Here we examined the effect of repeated injections of IL-15 on the development of diabetes in NOD mice. Injection of recombinant murine IL-15, once a day for 2 weeks, neither inhibited nor accelerated diabetes development in untreated NOD mice. However, treatment with IL-15 significantly reduced the incidence and delayed the onset of diabetes in NOD mice that were depleted of NK cells, while NK cell depletion alone had no protection against the disease development. The protective effect in IL-15-treated, NK cell-depleted NOD mice was associated with an increase in immunosuppressive activity of CD4(+)CD25(+) Tregs. IL-15 also enhanced Foxp3 expression in CD4(+)CD25(+) cells in an in vitro culture system, and such an effect of IL-15 was abrogated by IL-15-activated NK cells. Inhibition of IL-15-induced Foxp3 expression by IL-15-activated NK cells likely resulted from their IFN-gamma production, as recombinant IFN-gamma, or the culture supernatant of IL-15-activated wild-type mouse NK cells but not of IL-15-activated IFN-gamma-deficient NK cells, mediated a similar inhibition. IFN-gamma also diminished the stimulatory effect of IL-15 on Treg function in vitro. These results indicate that IL-15 has the potential to promote Treg function and protect against diabetes development in NOD mice, but such an activity can be eliminated by simultaneous activation of NK cells in IL-15-treated mice.

  17. Human herpesvirus-6 enhances natural killer cell cytotoxicity via IL-15.

    PubMed Central

    Flamand, L; Stefanescu, I; Menezes, J

    1996-01-01

    The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) suggesting that IL-15 secreted in response to viral infection was responsible for the observed effect. Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies. Using RT-PCR, we were able to detect IL-15 mRNA upregulation in purified monocyte and NK cell preparations. IL-15 protein synthesis was increased in response to HHV-6. Finally, addition of IL-15 to PBMC cultures was found to severely curtail HHV-6 expression. Taken together, our data suggest that enhanced NK activity in response to viral infection represent a natural anti-viral defense mechanism aimed at rapidly eliminating virus-infected cells. PMID:8617868

  18. [In vivo effect of recombined IL-15/Fc fusion protein on EAU].

    PubMed

    Xia, Zong-jing; Kong, Xiang-li; Zhang, Ping

    2008-11-01

    To test the effect of recombined IL-15/Fc on experimental autoimmune uveitis (EAU) in mice. EAU were induced in C57 mice by transferring activated T cells specific to the interphotoreceptor-binding protein (IRBP) 1-20 peptide. The mice were then treated with recombine IL-15/Fc fusion protein or IgG as controls. The severity of EAU were graded on a scale of 0 to 4 with half-point increment based on the type, number, and size of the lesions detected by funduscopic and HE staining. The IRBP1-20 sensitive CD8+T cells were isolated from the IRBP1-20 immune mice with auto-MACS. The in vitro effect of IL-15/Fc fusion protein on the proliferation, differentiation, expansion and production of inflammatory cytokines of the purified IRBP1-20 sensitive CD8+T cells were analyzed with 3HTdR, FACS and ELISA. IL-15/Fc fusion protein inhibited the activation, proliferation, expansion and production of inflammatory cytokines of the IRBP1-20 specific CD8+T cells, down regulated CD44(high)CD62L(low) effect and CD8+ CD62L(low) activated T cell subsets, and consequently decreased the severity of EAU. IL-15/Fc fusion proteins decrease the severity of EAU through inhibiting the proliferation, expansion, differentiation and production of inflammatory cytokines of CD8+ T cells.

  19. IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities.

    PubMed

    Orinska, Zane; Maurer, Marcus; Mirghomizadeh, Farhad; Bulanova, Elena; Metz, Martin; Nashkevich, Natalia; Schiemann, Florian; Schulmistrat, Jan; Budagian, Vadim; Giron-Michel, Julien; Brandt, Ernst; Paus, Ralf; Bulfone-Paus, Silvia

    2007-08-01

    Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly. Deletion of Il15 in mice markedly increases chymase activities, leading to greater MC bactericidal responses, increased processing and activation of neutrophil-recruiting chemokines, and significantly higher survival rates of mice after septic peritonitis. By showing that intracellular IL-15 acts as a specific negative transcriptional regulator of a mouse MC chymase (mast cell protease-2), we provide evidence that defined MC protease activity is transcriptionally regulated by an intracellularly retained cytokine. Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis.

  20. Tumor necrosis factor-{alpha} enhances IL-15-induced natural killer cell differentiation

    SciTech Connect

    Lee, Jiwon; Lee, Suk Hyung; Shin, Nara; Jeong, Mira; Kim, Mi Sun; Kim, Mi Jeong; Yoon, Suk Ran; Chung, Jin Woong; Kim, Tae-Don; Choi, Inpyo

    2009-09-04

    The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-{alpha} (TNF-{alpha}) is a positive regulator of NK cell differentiation. TNF-{alpha} augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-{alpha} alone also induced NK cell maturation as well as IL-15. TNF-{alpha} also increased IFN-{gamma} production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-{alpha} and IL-15. In addition, TNF-{alpha} increased nuclear factor-kappa B (NF-{kappa}B) activity in NK cells and inhibition of NF-{kappa}B impeded TNF-{alpha}-enhanced NK cell maturation. Overall, these data suggest that TNF-{alpha} significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-{kappa}B activity.

  1. Interleukin (IL)-2 and IL-15 have different effects on human natural killer lymphocytes.

    PubMed

    Pillet, Anne-Hélène; Thèze, Jacques; Rose, Thierry

    2011-11-01

    Although interleukin (IL)-2 and IL-15 share the common signal transducing receptor chains IL-2Rβ and γ(c) and give rise to the same signaling patterns in human natural killer (NK) cells in vitro, they differ in their effects on the development, activation, and proliferation of these cells in vivo. We have previously demonstrated that the activation of NK cells induces a cellular program characterized by the sequential transcription-regulated expression of IL-15 and IL-2 high-affinity receptors. We demonstrate here that these receptors induce different responses. IL-15 sustains the expression of its high-affinity receptor, leading to long-lasting STAT5 phosphorylation and BCL2 expression. By contrast, IL-2 induces the rapid disappearance of IL-2Rα and γ(c) chains when the gene transcription is downregulated, shutting down IL-2-responses as demonstrated by the absence of STAT5 phosphorylation and BCL2 expression.

  2. IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells

    PubMed Central

    Krolopp, James E.; Thornton, Shantaé M.; Abbott, Marcia J.

    2016-01-01

    Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK) and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5) were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism. PMID:28066259

  3. IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells.

    PubMed

    Krolopp, James E; Thornton, Shantaé M; Abbott, Marcia J

    2016-01-01

    Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK) and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5) were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism.

  4. The unconventional expression of IL-15 and its role in NK cell homeostasis.

    PubMed

    Huntington, Nicholas D

    2014-03-01

    Natural killer (NK) cells are the founding members of the innate lymphoid cell family and contribute to the rapid production of inflammatory mediators upon pathogen detection. The evolution of receptors for self major histocompatibility complex-I and stress-induced ligands also bestows upon NK cells an important effector role in the clearance of virus-infected and transformed cells. NK cells are dependent on the pleiotropic cytokine interleukin (IL)-15 for their development, differentiation and optimal function. Here I review the regulation of IL-15 in vivo, its role in driving NK cell differentiation and discuss the function of NK cell diversification with regard to innate immunity.

  5. IL-15 Mediates Mitochondrial Activity through a PPARδ-Dependent-PPARα-Independent Mechanism in Skeletal Muscle Cells

    PubMed Central

    2016-01-01

    Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPARα and/or PPARδ as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPARα inhibitor (GW-6471), a PPARδ inhibitor (GSK-3787), or both IL-15 and the inhibitors. IL-15 increased mitochondrial activity and induced PPARα, PPARδ, PGC1α, PGC1β, UCP2, and Nrf1 expression. There was no effect of inhibiting PPARα, in combination with IL-15, on the aforementioned mRNA levels except for PGC1β and Nrf1. However, with PPARδ inhibition, IL-15 failed to induce the expression levels of PGC1α, PGC1β, UCP2, and Nrf1. Further, inhibition of PPARδ abolished IL-15 induced increases in citrate synthase activity, ATP production, and overall mitochondrial activity. IL-15 had no effects on mitochondrial biogenesis. Our data indicates that PPARδ activity is required for the beneficial metabolic effects of IL-15 signaling in SKM. PMID:27738421

  6. Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling.

    PubMed

    Neely, Graham G; Epelman, Slava; Ma, Ling Ling; Colarusso, Pina; Howlett, Christopher J; Amankwah, Ernest K; McIntyre, Amanda C; Robbins, Stephen M; Mody, Christopher H

    2004-04-01

    IL-15 is a short chain, four-alpha helix cytokine that shares some biological function with IL-2. One striking difference between IL-2 and IL-15 is the ability of monocytes to express IL-15 on their cell surface after activation. In the current study we have investigated the ability of human monocyte cell surface IL-15 to participate in reverse signaling. Cross-linking anti-IL-15 Abs were used as a surrogate ligand for surface IL-15 engagement. Ligation of cell surface-expressed IL-15 induced monocyte adhesion that required the activity of small m.w. GTPases. Reverse signals through surface IL-15 activated the Rho-GTPase Rac3. In addition, engagement of cell surface IL-15 was found to activate a number of signaling pathways, including both extracellular signal-regulated kinase 1/2 and p38, and resulted in the secretion of IL-8. IL-8 production required mitogen-activated protein kinase activity. Thus, the current study has established that cell surface IL-15 is more than just a ligand; it can function as a receptor and participate in reverse signaling that results in cellular adhesion and production of inflammatory cytokines.

  7. IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection

    PubMed Central

    Younes, Souheil-Antoine; Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Reynaldi, Arnold; Estes, Jacob D.; Deleage, Claire; Lucero, Carissa; Anderson, Jodi; Schacker, Timothy W.; Davenport, Miles P.; McCune, Joseph M.; Hunt, Peter W.; Lee, Sulggi A.; Debernardo, Robert L.; Jacobson, Jeffrey M.; Canaday, David H.; Sekaly, Rafick-Pierre; Sieg, Scott F.; Lederman, Michael M.

    2016-01-01

    In HIV-1–infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1–infected patients. Compared with healthy controls, untreated HIV-1–infected patients have an increased population of proliferating, granzyme B+, CD8+ T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1–infected patients correlated with circulating CD8+ T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which predicts disease progression in untreated HIV-1–infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linked to increased morbidity and mortality in treated patients. PMID:27322062

  8. Recombinant Newcastle disease virus expressing IL15 demonstrates promising antitumor efficiency in melanoma model

    USDA-ARS?s Scientific Manuscript database

    Recombinant Newcastle Disease Virus (rNDV) has shown oncolytic therapeutic effect in preclinical studies. Previous data indicate that rNDV carrying IL2 has shown promise in cancer therapy. Due to the significant side effects of IL2, IL15 has been introduced into cancer therapy. A number of studies h...

  9. Proliferation-Linked Apoptosis of Adoptively Transferred T Cells after IL-15 Administration in Macaques

    PubMed Central

    Berger, Carolina; Berger, Michael; Beard, Brian C.; Kiem, Hans-Peter; Gooley, Theodore A.; Riddell, Stanley R.

    2013-01-01

    The adoptive transfer of antigen-specific effector T cells is being used to treat human infections and malignancy. T cell persistence is a prerequisite for therapeutic efficacy, but reliably establishing a high-level and durable T cell response by transferring cultured CD8+ T cells remains challenging. Thus, strategies that promote a transferred high-level T cell response may improve the efficacy of T cell therapy. Lymphodepletion enhances persistence of transferred T cells in mice in part by reducing competition for IL-15, a common γ-chain cytokine that promotes T cell memory, but lymphodepleting regimens have toxicity. IL-15 can be safely administered and has minimal effects on CD4+ regulatory T cells at low doses, making it an attractive adjunct in adoptive T cell therapy. Here, we show in lymphoreplete macaca nemestrina, that proliferation of adoptively transferred central memory-derived CD8+ effector T (TCM/E) cells is enhanced in vivo by administering IL-15. TCM/E cells migrated to memory niches, persisted, and acquired both central memory and effector memory phenotypes regardless of the cytokine treatment. Unexpectedly, despite maintaining T cell proliferation, IL-15 did not augment the magnitude of the transferred T cell response in blood, bone marrow, or lymph nodes. T cells induced to proliferate by IL-15 displayed increased apoptosis demonstrating that enhanced cycling was balanced by cell death. These results suggest that homeostatic mechanisms that regulate T cell numbers may interfere with strategies to augment a high-level T cell response by adoptive transfer of CD8+ TCM/E cells in lymphoreplete hosts. PMID:23418547

  10. Effect of IL-7 and IL-15 on T cell phenotype in myelodysplastic syndromes.

    PubMed

    Dong, Wen; Ding, Tingting; Wu, Lei; Ren, Xiubao; Epling-Burnette, P K; Yang, Lili

    2016-05-10

    Aberrant T cell phenotype is one of the characteristics of myelodysplastic syndromes (MDS). In this study, we detected an increased concentration of IL-15 in the plasma of MDS patients (n = 20) compared with that in the plasma of healthy controls (n = 20). In MDS patients, reduced naïve CD4+ and CD8+ T cells [16.11 ± 6.56 vs. 24.11 ± 7.18 for CD4+ T cells (p < 0.001) and 13.15 ± 5.67 vs. 23.51 ± 6.25 for CD8+ T cells (p < 0.001)] were observed. The reduced naïve and increased effector memory T cells were significantly correlated with IL-15 plasma level. Then, the effect of IL-15 and IL-7 was tested in vitro. Peripheral blood mononuclear cells from MDS were treated for 15 days with IL-15. This treatment significantly decreased naïve CD4+ (p < 0.001) and CD8+ (p < 0.001) T cells and correspondingly increased terminal memory CD4+ and CD8+ T cells (p < 0.001). Treatment with IL-7 increased naïve CD4+ (p < 0.05) and CD8+ (p < 0.001) T cells. Our results indicated that exposure to high levels of IL-15 may be involved in the T cell phenotype conversion observed in MDS. IL-7 may be one of the promising therapeutic candidates for recovering the effector immune compartment in MDS patients.

  11. The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL-15/IL-15Rα treatment

    PubMed Central

    Nair, Savita; Fang, Min; Sigal, Luis J

    2015-01-01

    Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, and autoimmune diseases. Natural killer (NK) cells are bone marrow-derived lymphocytes crucial for host defense against several infections and cancer. We have previously shown that compared to young, aged C57BL/6 mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by ectromelia virus. Here, we describe further age-related defects in NK cells including reduced proliferation in vivo, additional signs of immaturity, and dysregulated expression of activating and inhibitory receptors. Aging also alters the expression of collagen-binding integrins in conventional NK cells and the frequency and phenotype of liver tissue-resident NK cells. We additionally show that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Moreover, we demonstrate that in aged mice, treatment with complexes of the cytokine IL-15 and IL-15Rα induce massive expansion of the NK cells, but most of these NK cells remain immature and are unable to restore resistance to mousepox. The use of rodent model to understand immunosenescence may help the development of treatments to improve the immune fitness of the aged. Our work with NK cells should contribute toward this goal. PMID:25399821

  12. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8αα IELs1

    PubMed Central

    Ma, Lisa J.; Acero, Luis F.; Zal, Tomasz; Schluns, Kimberly S.

    2009-01-01

    IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Rα exclusively by the IECs (Villin/IL-15Rα Tg) was generated. Exclusive expression of IL-15Rα by the IECs restored all the deficiencies in the CD8αα+TCRαβ+and CD8αα+TCRγδ+ subsets that exist in the absence of IL-15Rα. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1lo IELs, which compose a majority of the IEL population. The differentiation of Thy1hiCD4−CD8− thymocytes into Thy1−CD8αα IELs was found to require IL-15Rα expression specifically by IECs and thus, provides evidence that differentiation of Thy1lo IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8αα+ T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1lo IELs. PMID:19553528

  13. Effect of anti-IL-15 administration on T cell and NK cell homeostasis in rhesus macaques

    PubMed Central

    DeGottardi, Maren Q.; Okoye, Afam A.; Vaidya, Mukta; Talla, Aarthi; Konfe, Audrie L.; Reyes, Matthew D.; Clock, Joseph A.; Duell, Derick M.; Legasse, Alfred W.; Sabnis, Amit; Park, Byung S.; Axthelm, Michael K.; Estes, Jacob D.; Reinmann, Keith A.; Sekaly, Rafick-Pierre; Picker, Louis J.

    2016-01-01

    IL-15 has been implicated as a key regulator of T and NK cell homeostasis in multiple systems; however, its specific role in maintaining peripheral T and NK cell populations relative to other gamma-chain (γc) cytokines has not been fully defined in primates. Here, we address this question by determining the effect of IL-15 inhibition with a rhesusized, anti-IL-15 mAb on T and NK cell dynamics in rhesus macaques. Strikingly, anti-IL-15 treatment resulted in rapid depletion of NK cells, and both CD4+ and CD8+ effector memory T cells (TEM) in blood and tissues, with little to no effect on naïve or central memory T cells. Importantly, whereas depletion of NK cells was nearly complete and maintained as long as anti-IL-15 treatment was given, TEM depletion was countered by the onset of massive TEM proliferation, which almost completely restored circulating TEM numbers. Tissue TEM, however, remained significantly reduced, and most TEM maintained very high turnover throughout anti-IL-15 treatment. In the presence of IL-15 inhibition, TEM became increasingly more sensitive to IL-7 stimulation in vivo, and transcriptional analysis of TEM in IL-15-inhibited monkeys revealed engagement of the JAK/STAT signaling pathway, suggesting alternative γc cytokine signaling may support TEM homeostasis in the absence of IL-15. Thus, IL-15 plays a major role in peripheral maintenance of NK cells and TEM. However, whereas most NK cell populations collapse in the absence of IL-15, TEM can be maintained in the face of IL-15 inhibition by the activity of other homeostatic regulators, most likely IL-7. PMID:27430715

  14. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.

    PubMed

    Ma, Lisa J; Acero, Luis F; Zal, Tomasz; Schluns, Kimberly S

    2009-07-15

    IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Ralpha exclusively by the IECs (Villin/IL-15Ralpha Tg) was generated. Exclusive expression of IL-15Ralpha by the IECs restored all the deficiencies in the CD8alphaalpha(+)TCRalphabeta(+)and CD8alphaalpha(+)TCRgammadelta(+) subsets that exist in the absence of IL-15Ralpha. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1(low) IELs, which compose a majority of the IEL population. The differentiation of Thy1(high)CD4(-)CD8(-) thymocytes into Thy1(-)CD8alphaalpha IELs was found to require IL-15Ralpha expression specifically by IECs and thus, provides evidence that differentiation of Thy1(low) IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8alphaalpha(+) T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1(low) IELs.

  15. Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype.

    PubMed

    Molanouri Shamsi, Mahdieh; Hassan, Zuhair Mohammad; Quinn, LeBris S; Gharakhanlou, Reza; Baghersad, Leila; Mahdavi, Mehdi

    2015-06-01

    Type 1 diabetes is associated with skeletal muscle atrophy. Skeletal muscle is an endocrine organ producing myokines such as interleukin-15 (IL-15) and interleukin-6 (IL-6) in response to contraction. These factors may mediate the effects of exercise on skeletal muscle metabolism and anabolic pathways. Lack of correlation between muscle IL-15 mRNA and protein levels after exercise training has been observed, while regulatory effects of IL-6 on IL-15 expression have also been suggested. This study determined post-exercise changes in muscle IL-15 and IL-6 mRNA expression and IL-15 protein levels in healthy and streptozotocin-induced diabetic rats in both the fast flexor hallucis longus (FHL) and slow soleus muscles. Resistance training preserved FHL muscle weight in diabetic rats and increased IL-15 protein levels in both the soleus and FHL muscles. However, the temporal pattern of this response was distinct in normal and diabetic rats. Moreover, discordance between post-exercise muscle IL-15 mRNA and protein expression was observed in our study, and diabetes suppressed post-exercise increases in FHL muscle IL-6 mRNA expression. Our study indicates that training, skeletal muscle phenotype, and metabolic status all influence the temporal pattern of post-exercise changes in IL-15 expression. Muscle IL-15 protein levels increase following training, suggesting this may be an adaptation contributing to increased capacity for secretion of this myokine that is not depressed by the diabetic state.

  16. Another look at sterilization.

    PubMed

    Willson, P D

    1977-03-01

    R.T. Ravenhol, Director of Office of Population at the U.S. Agency for International Development (AID), reports that voluntary sterilization is currently the foremost means of fertility control in the world. According to AID estimates, 65,000,000 couples had chosen voluntary sterilization by the end of 1975. In order to expand its support for voluntary sterilization, AID wants to offer more of its resources to services, equipment, biomedical research, physician training, and public education. The International Project of the Association for Voluntary Sterilization has been most active in the provision of voluntary sterilization. Funded by AID it has spent over $6 million on voluntary sterilization services, equipment, physician training, and conferences in over 50 countries since it was established in 1972. There is concern that the current acceptance of voluntary sterilization maybe jeopardized by lack of understanding about and sensitivity to sterilization's use. Voluntary and compulsory sterilization are at opposite ends of a spectrum, and for those involved in family planning in developing countries, there is the question of whether there is really massive demand for voluntary sterilization in developing countries and whether sterilization is truly voluntary. There has also been concern about voluntarism and informed consent in the U.S. domestic programs, and this has affected international projects. To stress the importance of voluntarism, AID contracts and grants, effective 1977, must include an extensive statement regarding voluntarism to ensure compliance with the court decision prohibiting federally funded sterilizations for minors and mental or legal incompetents. Additionally, AID contracts must require documented informed consent, and individuals choosing sterilizations need to receive a description of the risks and benefits as well as a statement that the procedure is irreversible.

  17. Postpartum Sterilization

    MedlinePlus

    ... How is postpartum sterilization performed? • What kind of anesthesia is used for postpartum sterilization? • How long does ... with stitches and a bandage. What kind of anesthesia is used for postpartum sterilization? Often, the type ...

  18. IL-15 receptor α signaling constrains the development of IL-17–producing γδ T cells

    PubMed Central

    Colpitts, Sara L.; Puddington, Lynn; Lefrançois, Leo

    2015-01-01

    The development and homeostasis of γδ T cells is highly dependent on distinct cytokine networks. Here we examine the role of IL-15 and its unique receptor, IL-15Rα, in the development of IL-17–producing γδ (γδ-17) T cells. Phenotypic analysis has shown that CD44high γδ-17 cells express IL-15Rα and the common gamma chain (CD132), yet lack the IL-2/15Rβ chain (CD122). Surprisingly, we found an enlarged population of γδ-17 cells in the peripheral and mesenteric lymph nodes of adult IL-15Rα KO mice, but not of IL-15 KO mice. The generation of mixed chimeras from neonatal thymocytes indicated that cell-intrinsic IL-15Rα expression was required to limit IL-17 production by γδ T cells. γδ-17 cells also were increased in the peripheral lymph nodes of transgenic knock-in mice, where the IL-15Rα intracellular signaling domain was replaced with the intracellular portion of the IL-2Rα chain (that lacks signaling capacity). Finally, an analysis of neonatal thymi revealed that the CD44lo/int precursors of γδ-17 cells, which also expressed IL-15Rα, were increased in newborn mice deficient in IL-15Rα signaling, but not in IL-15 itself. Thus, these findings demonstrate that signaling through IL-15Rα regulates the development of γδ-17 cells early in ontogeny, with long-term effects on their peripheral homeostasis in the adult. PMID:26195801

  19. Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

    PubMed Central

    Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

    2015-01-01

    During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential. PMID:25124553

  20. IL-15 Harnesses Pro-inflammatory Function of TEMRA CD8 in Kidney-Transplant Recipients.

    PubMed

    Tilly, Gaëlle; Doan-Ngoc, Tra-My; Yap, Michelle; Caristan, Aurélie; Jacquemont, Lola; Danger, Richard; Cadoux, Marion; Bruneau, Sarah; Giral, Magali; Guerif, Pierrick; Nicol, Bryan; Garcia, Alexandra; Laplaud, David-Axel; Brouard, Sophie; Pecqueur Hellman, Claire; Degauque, Nicolas

    2017-01-01

    The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM). IL-15 induces antiapoptotic signals and promotes proliferation dependent of PI3K/Akt, MAPK, and ERK pathways. Without ex vivo stimulation, TEMRA cells are metabolically more active than naive and EM, as shown by their high ATP reservoir and a high expression of genes involved in glycolysis, glutaminolysis, and the Pentose Phosphate Pathway. Upon stimulation, TEMRA adapt their metabolism by sustaining an increased mitochondrial respiration and glycolysis. Finally, we show that the inhibition of glycolysis is highly effective in preventing endothelial inflammation induced by TEMRA from KT recipients. Together, our findings highlight the metabolic fitness that tightly regulates the immune function of TEMRA in physiological and pathogenic situations.

  1. Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins.

    PubMed

    Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

    2015-01-01

    During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential.

  2. Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation.

    PubMed

    Castillo, Eliseo F; Acero, Luis F; Stonier, Spencer W; Zhou, Dapeng; Schluns, Kimberly S

    2010-10-07

    Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells was crucial for generating normal number of iNKTs in the thymus, whereas both hematopoietic and parenchymal cells regulated iNKT cell numbers in the periphery, particularly in the liver. Specifically, dendritic cells contributed to peripheral iNKT cell numbers by up-regulating Bcl-2 expression and promoting extrathymic iNKT cell ex-pansion and their homeostatic proliferation. Whether IL-15 affects functional maturation of iNKT cells was also examined. In IL-15Rα(-/-) mice, CD44(High)NK1.1(+) iNKT cells displayed decreased T-bet expression and in response to α-galactosylceramide, had deficient interferon-γ expression. Such defects could be reversed by exogenous IL-15 signals. Overall, these studies identify stage-specific functions of IL-15, which are determined by the tissue microenvironment and elucidate the importance of IL-15 in functional maturation.

  3. Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation

    PubMed Central

    Castillo, Eliseo F.; Acero, Luis F.; Stonier, Spencer W.; Zhou, Dapeng

    2010-01-01

    Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells was crucial for generating normal number of iNKTs in the thymus, whereas both hematopoietic and parenchymal cells regulated iNKT cell numbers in the periphery, particularly in the liver. Specifically, dendritic cells contributed to peripheral iNKT cell numbers by up-regulating Bcl-2 expression and promoting extrathymic iNKT cell ex-pansion and their homeostatic proliferation. Whether IL-15 affects functional maturation of iNKT cells was also examined. In IL-15Rα−/− mice, CD44HighNK1.1+ iNKT cells displayed decreased T-bet expression and in response to α-galactosylceramide, had deficient interferon-γ expression. Such defects could be reversed by exogenous IL-15 signals. Overall, these studies identify stage-specific functions of IL-15, which are determined by the tissue microenvironment and elucidate the importance of IL-15 in functional maturation. PMID:20581314

  4. Differential effects of IL-15 on the generation, maintenance and cytotoxic potential of adaptive cellular responses induced by DNA vaccination.

    PubMed

    Li, Jinyao; Valentin, Antonio; Ng, Sinnie; Beach, Rachel Kelly; Alicea, Candido; Bergamaschi, Cristina; Felber, Barbara K; Pavlakis, George N

    2015-02-25

    IL-15 is an important cytokine for the regulation of lymphocyte homeostasis. However, the role of IL-15 in the generation, maintenance and cytotoxic potential of antigen specific T cells is not fully understood. Because the route of antigenic delivery and the vaccine modality could influence the IL-15 requirement for mounting and preserving cytotoxic T cell responses, we have investigated the immunogenicity of DNA-based vaccines in IL-15 KO mice. DNA vaccination with SIV Gag induced antigen-specific CD4(+) and CD8(+) T cells in the absence of IL-15. However, the absolute number of antigen-specific CD8(+) T cells was decreased in IL-15 KO mice compared to WT animals, suggesting that IL-15 is important for the generation of maximal number of antigen-specific CD8(+) T cells. Interestingly, antigen-specific memory CD8 cells could be efficiently boosted 8 months after the final vaccination in both WT and KO strains of mice, suggesting that the maintenance of antigen-specific long-term memory T cells induced by DNA vaccination is comparable in the absence and presence of IL-15. Importantly, boosting by DNA 8-months after vaccination revealed severely reduced granzyme B content in CD8(+) T cells of IL-15 KO mice compared to WT mice. This suggests that the cytotoxic potential of the long-term memory CD8(+) T cells is impaired. These results suggest that IL-15 is not essential for the generation and maintenance of adaptive cellular responses upon DNA vaccination, but it is critical for the preservation of maximal numbers and for the activity of cytotoxic CD8(+) T cells. Published by Elsevier Ltd.

  5. Hippocampus-specific deficiency of IL-15Rα contributes to greater anxiety-like behaviors in mice.

    PubMed

    Nguyen, Linda; Bohlen, Joseph; Stricker, Janelle; Chahal, Ikttesh; Zhang, Hanting; Pistilli, Emidio E

    2016-11-11

    A hippocampus-specific IL15RαKO mouse (hipIl15ra (fl/fl) /Cre(+)) was generated to test the hypothesis that the targeted deletion of interleukin-15 receptor alpha (IL-15Rα) in the hippocampus contributes to altered behavior, including greater levels of anxiety and ambulatory activity. Using Cre-loxP, exons 2 and 3 of the IL-15Rα gene were excised within the hippocampus, while normal expression was maintained within the rest of the brain. In the open field test (OFT), hipIl15ra (fl/fl) /Cre(+) spent a greater amount of time in the periphery and less time in the central portions of the chamber, and there was also a noticeable trend for decreased rearing activity; these behaviors are consistent with greater levels of anxiety-like behavior in these mice. However, there were no differences in the overall locomotor counts in the OFT when comparing hipIl15ra (fl/fl) /Cre(+) mice to their littermate controls. These data implicate IL-15-related signaling within the hippocampus has a role in anxiety-like behavior.

  6. New Approach for Producing and Purifying IL-15 Heterodimers That Have Potent Immune Effect | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer Cytokines are proteins that play a crucial role in the human immune system by delivering messages that trigger the activation of immune cells to fight off attacks from viruses or other invaders. Cristina Bergamaschi, Ph.D., NCI Center for Cancer Research, has been studying the mechanism of expression and function of a cytokine known as interleukin-15 (IL-15) for the last five years, in collaboration with Elena Chertova, Ph.D., and other researchers in the Retroviral Protein Chemistry Core (RPCC) of the AIDS and Cancer Virus Program (ACVP), Frederick National Laboratory for Cancer Research.

  7. New Approach for Producing and Purifying IL-15 Heterodimers That Have Potent Immune Effect | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer Cytokines are proteins that play a crucial role in the human immune system by delivering messages that trigger the activation of immune cells to fight off attacks from viruses or other invaders. Cristina Bergamaschi, Ph.D., NCI Center for Cancer Research, has been studying the mechanism of expression and function of a cytokine known as interleukin-15 (IL-15) for the last five years, in collaboration with Elena Chertova, Ph.D., and other researchers in the Retroviral Protein Chemistry Core (RPCC) of the AIDS and Cancer Virus Program (ACVP), Frederick National Laboratory for Cancer Research.

  8. International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 8 on Sterility Test General Chapter; availability. Notice.

    PubMed

    2009-12-22

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 8: Sterility Test General Chapter.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides the results of the ICH Q4B evaluation of the Sterility Test General Chapter harmonized text from each of the three pharmacopoeias (United States, European, and Japanese) represented by the Pharmacopoeial Discussion Group (PDG). The guidance conveys recognition of the three pharmacopoeial methods by the three ICH regulatory regions and provides specific information regarding the recognition. The guidance is intended to recognize the interchangeability between the local regional pharmacopoeias, thus avoiding redundant testing in favor of a common testing strategy in each regulatory region. In the Federal Register of February 21, 2008 (73 FR 9575), FDA made available a guidance on the Q4B process entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions."

  9. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  10. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  11. Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor

    PubMed Central

    Ernestam, Sofia; af Klint, Erik; Catrina, Anca Irinel; Sundberg, Erik; Engström, Marianne; Klareskog, Lars; Ulfgren, Ann-Kristin

    2006-01-01

    Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1α, IL-1ß and IFN-γ, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade. PMID:16507118

  12. Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner.

    PubMed

    Anguille, Sébastien; Van Acker, Heleen H; Van den Bergh, Johan; Willemen, Yannick; Goossens, Herman; Van Tendeloo, Viggo F; Smits, Evelien L; Berneman, Zwi N; Lion, Eva

    2015-01-01

    The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as "IL-15 DCs", with the capacity to stimulate NK cells. In a head-to-head comparison with "IL-4 DCs" used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on "gold-standard" IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies.

  13. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

    SciTech Connect

    Yan, Chen; Jie, Leng; Yongqi, Wang; Weiming, Xiao; Juqun, Xi; Yanbing, Ding; Li, Qian; Xingyuan, Pan; Mingchun, Ji; Weijuan, Gong

    2015-07-31

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.

  14. IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking

    PubMed Central

    Nolz, Jeffrey C.; Harty, John T.

    2014-01-01

    Memory and naive CD8+ T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8+ T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8+ T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8+ T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues. Following infection, antigen-specific effector CD8+ T cells strongly expressed core 2 O-glycans, but this glycosylation pattern was lost by most memory CD8+ T cells. After unrelated infection or inflammatory challenge, memory CD8+ T cells synthesized core 2 O-glycans independently of antigen restimulation. The presence of core 2 O-glycans subsequently directed these cells to inflamed tissue. Memory and naive CD8+ T cells exhibited the opposite pattern of epigenetic modifications at the Gcnt1 locus, which encodes the enzyme that initiates core 2 O-glycan synthesis. The open chromatin configuration in memory CD8+ T cells permitted de novo generation of core 2 O-glycans in a TCR-independent, but IL-15–dependent, manner. Thus, IL-15 stimulation promotes antigen-experienced memory CD8+ T cells to generate core 2 O-glycans, which subsequently localize them to inflamed tissues. These findings suggest that CD8+ memory T cell trafficking potentially can be manipulated to improve host defense and immunotherapy. PMID:24509081

  15. High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

    SciTech Connect

    Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.

    2009-10-10

    Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-gamma (0.5 mg) and the proliferation of CD4{sup +} and CD8{sup +} T cells, as well as T{sub CM} levels in proliferating CD8{sup +} T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4{sup +} and CD8{sup +} T cells and T{sub CM} levels in the proliferating CD4{sup +} and CD8{sup +} T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.

  16. Lack of IL-15 results in the suboptimal priming of CD4+ T cell response against an intracellular parasite.

    PubMed

    Combe, Crescent L; Moretto, Magali M; Schwartzman, Joseph D; Gigley, Jason P; Bzik, David J; Khan, Imtiaz A

    2006-04-25

    IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced antigen-specific proliferation, was due to defective priming of the T cell subset by dendritic cells (DCs) of these animals. When stimulated with antigen-pulsed DCs from WT mice, CD4+ T cells from IL-15-/- mice were primed optimally, and robust proliferation of these cells was observed. A defect in the DCs of knockout mice was further confirmed by their reduced ability to produce IL-12 upon stimulation with Toxoplasma lysate antigen. Addition of exogenous IL-15 to DC cultures from knockout mice led to increased IL-12 production by these cells and restored their ability to prime an optimal parasite-specific CD4+ T cell response. To our knowledge, this is the first demonstration of the role of IL-15 in the development of CD4+ T cell immunity against an intracellular pathogen. Furthermore, based on these observations, targeting of IL-15 should have a beneficial effect on individuals suffering from CD4+ T cell-mediated autoimmune diseases.

  17. Comparison of the super agonist complex, ALT-803, to IL-15 as cancer immunotherapeutics in animal models

    PubMed Central

    Xu, Wenxin; Hong, Hao; Webb, Gabriela M.; Chen, Xiaoyue; Liu, Bai; Zhu, Xiaoyun; Wen, Jinghai; You, Lijing; Kong, Lin; Edwards, Ana C.; Han, Kaiping; Shi, Sixiang; Alter, Sarah; Sacha, Jonah B.; Jeng, Emily K.; Cai, Weibo; Wong, Hing C.

    2015-01-01

    Interleukin-15 (IL-15), a potent stimulant of CD8+ T and NK cells, is a promising cancer immunotherapeutic. ALT-803 is a complex of an IL-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein that was found to exhibit enhanced biologic activity in vivo with a substantially longer serum half-life than recombinant IL-15. A single intravenous dose of ALT-803, but not IL-15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. In this study, we extended these findings to demonstrate the superior antitumor activity of ALT-803 over IL-15 in mice bearing subcutaneous B16F10 melanoma tumors and CT26 colon carcinoma metastases. Tissue biodistribution studies in mice also showed much greater retention of ALT-803 in the lymphoid organs compared to IL-15, consistent with its highly potent immunostimulatory and antitumor activities in vivo. Weekly dosing with 1 mg/kg ALT-803 in C57BL/6 mice was well-tolerated, yet capable of increasing peripheral blood lymphocyte, neutrophil and monocyte counts by >8-fold. ALT-803 dose-dependent stimulation of immune cell infiltration into the lymphoid organs was also observed. Similarly, cynomolgus monkeys treated weekly with ALT-803 showed dose-dependent increases of peripheral blood lymphocyte counts, including NK, CD4+, and CD8+ memory T cell subsets. In vitro studies demonstrated ALT-803-mediated stimulation of mouse and human immune cell proliferation and IFN-γ production without inducing a broad-based release of other proinflammatory cytokines (i.e., cytokine storm). Based on these results, a weekly dosing regimen of ALT-803 has been implemented in multiple clinical studies to evaluate the dose required for effective immune cell stimulation in humans. PMID:26511282

  18. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells

    PubMed Central

    Hurton, Lenka V.; Singh, Harjeet; Najjar, Amer M.; Switzer, Kirsten C.; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A.; Champlin, Richard E.; Cooper, Laurence J. N.

    2016-01-01

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR+ T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19+ leukemia. Long-lived T cells were CD45ROnegCCR7+CD95+, phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR+ T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials. PMID:27849617

  19. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity.

    PubMed

    Yan, Chen; Jie, Leng; Yongqi, Wang; Weiming, Xiao; Juqun, Xi; Yanbing, Ding; Li, Qian; Xingyuan, Pan; Mingchun, Ji; Weijuan, Gong

    2015-07-31

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8(+) T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy.

  20. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

    PubMed

    Hurton, Lenka V; Singh, Harjeet; Najjar, Amer M; Switzer, Kirsten C; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2016-11-29

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19(+) leukemia. Long-lived T cells were CD45RO(neg)CCR7(+)CD95(+), phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR(+) T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials.

  1. IL-15 dependent induction of IL-18 secretion as a feedback mechanism controlling human MAIT-cell effector functions.

    PubMed

    Sattler, Arne; Dang-Heine, Chantip; Reinke, Petra; Babel, Nina

    2015-08-01

    Mucosal-associated invariant T (MAIT) cells are characterized by an invariant TCRVα7.2 chain recognizing microbial vitamin B metabolites presented by the MHC-Ib molecule MR1. They are mainly detectable in the CD8(+) and CD8(-) CD4(-) "double negative" T-cell compartments of mammals and exhibit both Th1- and Th17-associated features. As MAIT cells show a tissue-homing phenotype and operate at mucosal surfaces with myriads of pathogenic encounters, we wondered how IL-15, a multifaceted cytokine being part of the intestinal mucosal barrier, impacts on their functions. We demonstrate that in the absence of TCR cross-linking, human MAIT cells secrete IFN-γ, increase perforin expression and switch on granzyme B production in response to IL-15. As this mechanism was dependent on the presence of CD14(+) cells and sensitive to IL-18 blockade, we identified IL-15 induced IL-18 production by monocytes as an inflammatory, STAT5-dependent feedback mechanism predominantly activating the MAIT-cell population. IL-15 equally affects TCR-mediated MAIT-cell functions since it dramatically amplifies bacteria-induced IFN-γ secretion, granzyme production, and cytolytic activity at early time points, an effect being most pronounced under suboptimal TCR stimulation conditions. Our data reveal a new quality of IL-15 as player in an inflammatory cytokine network impacting on multiple MAIT-cell functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Sterilization System

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Cox Sterile Products, Inc.'s Rapid Heat Transfer Sterilizer employs a heat exchange process that induces rapid air movement; the air becomes the heat transfer medium, maintaining a uniform temperature of 375 degrees Fahrenheit. It features pushbutton controls for three timing cycles for different instrument loads, a six-minute cycle for standard unpackaged instruments, eight minutes for certain specialized dental/medical instruments and 12 minutes for packaged instruments which can then be stored in a drawer in sterile condition. System will stay at 375 degrees all day. Continuous operation is not expensive because of the sterilizer's very low power requirements.

  3. BASICS OF STERILE COMPOUNDING: Sterilization Methods in Sterile Product Manufacturing.

    PubMed

    Akers, Michael J

    2015-01-01

    Sterilization methods to produce sterile preparations include heat, gas, radiation, and filtration. This article focuses on heat, gas, and radiation sterilization, plus a brief introduction to bright-light sterilization. Microbiology basics and microbial death kinetics, key to understanding why these sterilization methods work, will also be briefly discussed. Filtration sterilization will be covered in a separate article.

  4. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer

    SciTech Connect

    Heon, Elise K.; Wulan, Hasi; Macdonald, Loch P.; Malek, Adel O.; Braunstein, Glenn H.; Eaves, Connie G.; Schattner, Mark D.; Allen, Peter M.; Alexander, Michael O.; Hawkins, Cynthia A.; McGovern, Dermot W.; Freeman, Richard L.; Amir, Eitan P.; Huse, Jason D.; Zaltzman, Jeffrey S.; Kauff, Noah P.; Meyers, Paul G.; Gleason, Michelle H.; Overholtzer, Michael G.; Wiseman, Sam S.; and others

    2015-08-14

    IL-15 has pivotal roles in the control of CD8{sup +} memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. - Highlights: • We explored the effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells of breast cancer. • IL-15

  5. Muscle-specific deletion of exons 2 and 3 of the IL15RA gene in mice: effects on contractile properties of fast and slow muscles.

    PubMed

    O'Connell, Grant; Guo, Ge; Stricker, Janelle; Quinn, LeBris S; Ma, Averil; Pistilli, Emidio E

    2015-02-15

    Interleukin-15 (IL-15) is a putative myokine hypothesized to induce an oxidative skeletal muscle phenotype. The specific IL-15 receptor alpha subunit (IL-15Rα) has also been implicated in specifying this contractile phenotype. The purposes of this study were to determine the muscle-specific effects of IL-15Rα functional deficiency on skeletal muscle isometric contractile properties, fatigue characteristics, spontaneous cage activity, and circulating IL-15 levels in male and female mice. Muscle creatine kinase (MCK)-driven IL-15Rα knockout mice (mIl15ra(fl/fl)/Cre(+)) were generated using the Cre-loxP system. We tested the hypothesis that IL-15Rα functional deficiency in skeletal muscle would increase resistance to contraction-induced fatigue, cage activity, and circulating IL-15 levels. There was a significant effect of genotype on the fatigue curves obtained in extensor digitorum longus (EDL) muscles from female mIl15ra(fl/fl)/Cre(+) mice, such that force output was greater during the repeated contraction protocol compared with mIl15ra(fl/fl)/Cre(-) control mice. Muscles from female mIl15ra(fl/fl)/Cre(+) mice also had a twofold greater amount of the mitochondrial genome-specific COXII gene compared with muscles from mIl15ra(fl/fl)/Cre(-) control mice, indicating a greater mitochondrial density in these skeletal muscles. There was a significant effect of genotype on the twitch:tetanus ratio in EDL and soleus muscles from mIl15ra(fl/fl)/Cre(+) mice, such that the ratio was lower in these muscles compared with mIl15ra(fl/fl)/Cre(-) control mice, indicating a pro-oxidative shift in muscle phenotype. However, spontaneous cage activity was not different and IL-15 protein levels were lower in male and female mIl15ra(fl/fl)/Cre(+) mice compared with control. Collectively, these data support a direct effect of muscle IL-15Rα deficiency in altering contractile properties and fatigue characteristics in skeletal muscles.

  6. Increased CD8+ T cell memory to concurrent infection at the expense of increased erosion of pre-existing memory: the paradoxical role of IL-15.

    PubMed

    Chapdelaine, Yvan; Smith, Dean K; Pedras-Vasconcelos, Joao A; Krishnan, Lakshmi; Sad, Subash

    2003-11-15

    The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8(+) T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rbeta expression and increased frequency of IFN-gamma-secreting CD8(+) T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA(257-264)-specific CD8(+) T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA(257-264)-specific CD8(+) T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8(+) T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory.

  7. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner.

    PubMed

    Polansky, Julia K; Bahri, Rajia; Divivier, Mylene; Duitman, Erwin H; Vock, Christina; Goyeneche-Patino, Diego A; Orinska, Zane; Bulfone-Paus, Silvia

    2016-01-29

    The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.

  8. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner

    PubMed Central

    Polansky, Julia K.; Bahri, Rajia; Divivier, Mylene; Duitman, Erwin H.; Vock, Christina; Goyeneche-Patino, Diego A.; Orinska, Zane; Bulfone-Paus, Silvia

    2016-01-01

    The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8+ T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8+ T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of “free” IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired. PMID:26822794

  9. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15

    PubMed Central

    Oghumu, Steve; Terrazas, Cesar A.; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Satoskar, Abhay R.

    2015-01-01

    Innate CD8+ T cells are a heterogeneous population with developmental pathways distinct from conventional CD8+ T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8+ T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive transfer of IL-15 activated CXCR3+ innate CD8+ T cells conferred increased protection against Listeria monocytogenes infection in susceptible IFN-γ−/− mice compared with similarly activated CXCR3− subset. This was associated with enhanced proliferation and IFN-γ production in CXCR3+ cells. Further, CXCR3+ innate cells showed enhanced cytotoxicity against a tumor cell line in vitro. In depth analysis of the CXCR3+ subset showed increased gene expression of Ccl5, Klrc1, CtsW, GP49a, IL-2Rβ, Atp5e, and Ly6c but reduced IFN-γR2 and Art2b. Ingenuity pathway analysis revealed an up-regulation of genes associated with T-cell activation, proliferation, cytotoxicity, and translational initiation in CXCR3+ populations. Our results demonstrate that CXCR3 expression in innate CD8+ T cells defines a subset with enhanced cytotoxic potential and protective antibacterial immune functions. Immunotherapeutic approaches against infectious disease and cancer could utilize CXCR3+ innate CD8+ T-cell populations as novel clinical intervention strategies.—Oghumu, S., Terrazas, C. A., Varikuti, S., Kimble, J., Vadia, S., Yu, L., Seveau, S., Satoskar, A. R. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15. PMID:25466888

  10. NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation

    PubMed Central

    Yang, Meixiang; Chen, Shasha; Du, Juan; He, Junming; Wang, Yuande; Li, Zehua; Liu, Guangao; Peng, Wanwen; Zeng, Xiaokang; Li, Dan; Xu, Panglian; Guo, Wei; Chang, Zai; Wang, Song; Tian, Zhigang; Dong, Zhongjun

    2016-01-01

    Activation of metabolic signalling by IL-15 is required for natural killer (NK) cell development. Here we show that Tsc1, a repressor of mTOR, is dispensable for the terminal maturation, survival and function of NK cells but is critical to restrict exhaustive proliferation of immature NK cells and activation downstream of IL-15 during NK cell development. Tsc1 is expressed in immature NK cells and is upregulated by IL-15. Haematopoietic-specific deletion of Tsc1 causes a marked decrease in the number of NK cells and compromises rejection of ‘missing-self' haematopoietic tumours and allogeneic bone marrow. The residual Tsc1-null NK cells display activated, pro-apoptotic phenotype and elevated mTORC1 activity. Deletion of Raptor, a component of mTORC1, largely reverses these defects. Tsc1-deficient NK cells express increased levels of T-bet and downregulate Eomes and CD122, a subunit of IL-15 receptor. These results reveal a role for Tsc1-dependent inhibition of mTORC1 activation during immature NK cell development. PMID:27601261

  11. Sterile Neutrinos

    NASA Astrophysics Data System (ADS)

    Palazzo, Antonio

    2016-05-01

    Several anomalies recorded in short-baseline neutrino experiments suggest the possibility that the standard 3-flavor framework may be incomplete and point towards a manifestation of new physics. Light sterile neutrinos provide a credible solution to these puzzling results. Here, we present a concise review of the status of the neutrino oscillations within the 3+1 scheme, the minimal extension of the standard 3-flavor framework endowed with one sterile neutrino species. We emphasize the potential role of LBL experiments in the searches of CP violation related to sterile neutrinos and their complementarity with the SBL experiments.

  12. Durable cytotoxic immune responses against gp120 elicited by recombinant SV40 vectors encoding HIV-1 gp120 +/- IL-15.

    PubMed

    McKee, Hayley J; T'sao, Patricia Y; Vera, Maria; Fortes, Puri; Strayer, David S

    2004-08-23

    BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and cytotoxic memory were tested in direct cytotoxicity assays using unselected effector cells. Antibody vs. gp120 was measured in a binding assay. In both cases, targets were P815 cells that were stably transfected with gp120. RESULTS: Multiple injections of SV(gp120) elicited powerful anti-gp120 cytolytic activity (>70% specific lysis) by unselected spleen cells. Cells from multiply-immunized mice that were rested 1 year after their last injections still showed >60% gp120-specific lysis. Anti-gp120 antibody was first detected after 2 monthly injections of SV(gp120) and remained elevated thereafter. Adding SV(mIL-15) to the immunization regimen dramatically accelerated the development of memory cytolytic responses, with >/= 50% specific lysis seen 1 month after two treatments. IL-15 did not alter the development of antibody responses. CONCLUSIONS: Thus, rSV40s encoding antigens and immunostimulatory cytokines may be useful tools for priming and/or boosting immune responses against HIV.

  13. TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells

    PubMed Central

    Gupta, Rashmi; Boyle, Erin; Nieto, Jennifer; Lee, Hyunjoo; Stein, Joanna; Bandovic, Jela; Stankovic, Tatjana; Barrientos, Jacqueline; Kolitz, Jonathan E.; Allen, Steven L.; Rai, Kanti; Chu, Charles C.; Chiorazzi, Nicholas

    2015-01-01

    Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone’s Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this was true for B-CLL cells. Through a CFSE-based assay for quantitatively monitoring in vitro clonal proliferation/survival, we show that IL-15 precludes TLR-9–induced apoptosis and permits significant B-CLL clonal expansion regardless of the clone’s BCR mutation status. A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38+ cells within the blood-derived B-CLL population. Furthermore, a clone’s intrinsic potential for in vitro growth correlated directly with doubling time in blood, in the case of B-CLL with Ig H chain V region–unmutated BCR and <30% CD38+ cells in blood. Finally, in vitro high-proliferator status was statistically linked to diminished patient survival. These findings, together with immunohistochemical evidence of apoptotic cells and IL-15–producing cells proximal to B-CLL pseudofollicles in patient spleens, suggest that collaborative ODN and IL-15 signaling may promote in vivo B-CLL growth. PMID:26136429

  14. Tubal Sterilization

    MedlinePlus

    ... pregnancy. Tubal sterilization is a permanent form of birth control. It is one of the most effective options for preventing pregnancy. But it is difficult to reverse. It doesn’t protect against sexually ...

  15. Postpartum Sterilization

    MedlinePlus

    ... a few hours or days following delivery. For women who have had a cesarean delivery, it is done right after the baby is born. How is postpartum sterilization performed? For women who have had a vaginal delivery, a small ...

  16. Sterile neutrinos

    SciTech Connect

    Kopp, J.; Machado, P. A. N.

    2016-06-21

    We characterize statistically the indications of a presence of one or more light sterile neutrinos from MiniBooNE and LSND data, together with the reactor and gallium anomalies, in the global context. The compatibility of the aforementioned signals with null results from solar, atmospheric, reactor, and accelerator experiments is evaluated. We conclude that a severe tension is present in the global fit, and therefore the addition of eV-scale sterile neutrinos does not satisfactorily explain the anomalies.

  17. Sterile neutrinos

    NASA Astrophysics Data System (ADS)

    Kopp, J.; Machado, P. A. N.; Maltoni, M.; Schwetz, T.

    2016-06-01

    We characterize statistically the indications of a presence of one or more light sterile neutrinos from MiniBooNE and LSND data, together with the reactor and gallium anomalies, in the global context. The compatibility of the aforementioned signals with null results from solar, atmospheric, reactor, and accelerator experiments is evaluated. We conclude that a severe tension is present in the global fit, and therefore the addition of eV-scale sterile neutrinos does not satisfactorily explain the anomalies.

  18. miR-15b is Downregulated in Myasthenia Gravis Patients and Directly Regulates the Expression of Interleukin-15 (IL-15) in Experimental Myasthenia Gravis Mice.

    PubMed

    Shi, Lei; Liu, Tiantian; Zhang, Min; Guo, Yapei; Song, Changdong; Song, Dandan; Liu, Hengfang

    2015-06-19

    miR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG. Blood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model. qRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match. This study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.

  19. IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

    PubMed

    Yan, Wang; Fan, Weinv; Chen, Caijing; Wu, Yunqin; Fan, Zhenyi; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

    2016-10-10

    This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P < 0.05). In addition, IL-15 is proved to increase cell migration and nucleus expression of NF-kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels.

  20. Stimulation of Natural Killer Cell-Mediated Tumor Immunity by an IL15/TGFβ-Neutralizing Fusion Protein.

    PubMed

    Ng, Spencer; Deng, Jiusheng; Chinnadurai, Raghavan; Yuan, Shala; Pennati, Andrea; Galipeau, Jacques

    2016-10-01

    The clinical efficacy of immune cytokines used for cancer therapy is hampered by elements of the immunosuppressive tumor microenvironment such as TGFβ. Here we demonstrate that FIST15, a recombinant chimeric protein composed of the T-cell-stimulatory cytokine IL15, the sushi domain of IL15Rα and a TGFβ ligand trap, can overcome immunosuppressive TGFβ to effectively stimulate the proliferation and activation of natural killer (NK) and CD8(+) T cells with potent antitumor properties. FIST15-treated NK and CD8(+) T cells produced more IFNγ and TNFα compared with treatment with IL15 and a commercially available TGFβ receptor-Fc fusion protein (sTβRII) in the presence of TGFβ. Murine B16 melanoma cells, which overproduce TGFβ, were lysed by FIST15-treated NK cells in vitro at doses approximately 10-fold lower than NK cells treated with IL15 and sTβRII. Melanoma cells transduced to express FIST15 failed to establish tumors in vivo in immunocompetent murine hosts and could only form tumors in beige mice lacking NK cells. Mice injected with the same cells were also protected from subsequent challenge by unmodified B16 melanoma cells. Finally, mice with pre-established B16 melanoma tumors responded to FIST15 treatment more strongly compared with tumors treated with control cytokines. Taken together, our results offer a preclinical proof of concept for the use of FIST15 as a new class of biological therapeutics that can coordinately neutralize the effects of immunosuppressive TGFβ in the tumor microenvironment while empowering tumor immunity. Cancer Res; 76(19); 5683-95. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Hysteroscopic sterilization.

    PubMed

    Cooper, J M

    1992-06-01

    After a brief history of sterilization, this article is devoted to hysteroscopic techniques and instrumentation, and a presentation of hysteroscopic sterilization techniques: electrocoagulation techniques, hysteroscopic injection of chemicals, and hysteroscopically directed placement of intratubal mechanical devices (ceramic plugs, polyethylene plugs, preformed silicone plugs, nylon intratubal plugs, and formed-in-place silicone rubber plugs. Problems are identified that are common to all hysteroscopic sterilization techniques. There are also practical considerations which limit the development of hysteroscopic sterilization techniques, and these considerations are presented. Various means have been used historically to block the tubal ostia, including the insertion of nitric acid in 1984, but it was not until 1927 that the hysteroscope was used for sterilization. Hysteroscopy itself was discovered in 1869 for diagnosis of intrauterine diseases. Even with the hysteroscope and the 1934 procedure of using an electric current in the tubal ostia, hysteroscopic sterilization was little used. In 1973 a convention was convened to discuss the use of the procedure and the ramifications. Currently, the hysteroscope is a modified cytoscope with a 4 mm wide telescope with a fore-oblique lens, a 7 mm wide metallic sheath, a fiberoptic bundle for transmission of light, and additional instruments for intrauterine manipulation or surgical intervention. Under local anesthesia, sterilization is effected by 1) destruction of the interstitial portion of the oviduct by thermal energy, 2) injection techniques for the delivery of sclerosing substances or tissue adhesives, or 3) mechanical occlusive devices or plugs to block the oviduct. Recent uterine, cervical, or adnexal infections and pregnancy prevent the performance of sterilization, because infections are exacerbated by the procedure. Uterine perforation is a complication. Other complications involve allergic reactions to the

  2. The IL15 +96522 A>T functional polymorphism is related to the differentiation of Th17 cells and the severity of Hashimoto's disease.

    PubMed

    Arakawa, Y; Watanabe, M; Takemura, K; Inoue, N; Hidaka, Y; Iwatani, Y

    2017-04-01

    To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD. The serum levels of IL-15 were higher in individuals with the IL15 +96522 AA genotype than in those with the T allele, and they were also higher in patients with severe HD than in those with mild HD. On the other hand, the mRNA levels of IL-15 were not significantly different among individuals with each genotype of both SNPs. After incubation with recombinant human IL-15, the proportions of Th17 cells in CD4(+) cells were increased, and those of Treg cells in CD4(+) cells were maintained. Our study indicates that the IL15 +96522A/C polymorphism correlates with the severity of HD, most likely by increasing Th17 cells. © 2017 John Wiley & Sons Ltd.

  3. Sterile connector.

    PubMed

    Tenczar, F J

    1976-01-01

    Fabrication of a sterile connector for joining a supply source to an independent delivery location through a contaminated environment requires four design steps: 1) alignment of connector housings; 2) exclusion of the contaminated environment; 3) sterilization of the excluded region; and 4) penetration within the sterilized area followed by coupling of the protected internal conduits. Protective covers for connectors now in use may be modified to provide penetrable terminal barrier membranes that can be joined to exclude the environment. An adhesive containing an antimicrobiologic agent would set the stage for a controlled mechanical penetration of the decontaminated fused barriers. In another design concept, plastic barrier membranes without preliminary adhesions are simultaneously fused, sterilized, and penetrated by a nichrome wire heated to approximately 288 C. A system can be designed that is compatible, at the option of the user, with either of these methods. The more economical mechanical approach could then be used for parenteral fluid therapy while the nichrome wire technique would be reserved for more complex processing methods (frozen erythrocytes) or when storage of the resulting component is a factor.

  4. Two similar but distinct second intron fragments from tobacco AGAMOUS homologs confer identical floral organ-specific expression sufficient for generating complete sterility in plants

    USDA-ARS?s Scientific Manuscript database

    The carpel- and stamen-specific AtAGIP promoter derived from the Arabidopsis AGAMOUS (AG) second intron/enhancer is ideal for engineering complete sterility, but it is highly host-specific. To ascertain that a chimeric promoter with similar tissue specificity can be created for species other than A...

  5. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15.

    PubMed

    Oghumu, Steve; Terrazas, Cesar A; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Satoskar, Abhay R

    2015-03-01

    Innate CD8(+) T cells are a heterogeneous population with developmental pathways distinct from conventional CD8(+) T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8(+) T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive transfer of IL-15 activated CXCR3(+) innate CD8(+) T cells conferred increased protection against Listeria monocytogenes infection in susceptible IFN-γ(-/-) mice compared with similarly activated CXCR3(-) subset. This was associated with enhanced proliferation and IFN-γ production in CXCR3(+) cells. Further, CXCR3(+) innate cells showed enhanced cytotoxicity against a tumor cell line in vitro. In depth analysis of the CXCR3(+) subset showed increased gene expression of Ccl5, Klrc1, CtsW, GP49a, IL-2Rβ, Atp5e, and Ly6c but reduced IFN-γR2 and Art2b. Ingenuity pathway analysis revealed an up-regulation of genes associated with T-cell activation, proliferation, cytotoxicity, and translational initiation in CXCR3(+) populations. Our results demonstrate that CXCR3 expression in innate CD8(+) T cells defines a subset with enhanced cytotoxic potential and protective antibacterial immune functions. Immunotherapeutic approaches against infectious disease and cancer could utilize CXCR3(+) innate CD8(+) T-cell populations as novel clinical intervention strategies.

  6. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer.

    PubMed

    Heon, Elise K; Wulan, Hasi; Macdonald, Loch P; Malek, Adel O; Braunstein, Glenn H; Eaves, Connie G; Schattner, Mark D; Allen, Peter M; Alexander, Michael O; Hawkins, Cynthia A; McGovern, Dermot W; Freeman, Richard L; Amir, Eitan P; Huse, Jason D; Zaltzman, Jeffrey S; Kauff, Noah P; Meyers, Paul G; Gleason, Michelle H; Overholtzer, Michael G; Wiseman, Sam S; Streutker, Catherine D; Asa, Sylvia W; McAlindon, Timothy P; Newcomb, Polly O; Sorensen, Poul M; Press, Oliver A

    2015-08-14

    IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy.

  7. Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells.

    PubMed

    Chapoval, A I; Fuller, J A; Kremlev, S G; Kamdar, S J; Evans, R

    1998-12-15

    Previous studies have demonstrated that IL-15 administration after cyclophosphamide (CY) injection of C57BL/6J mice bearing the i.m. 76-9 rhabdomyosarcoma resulted in a significant prolongation of life. In the present study, we investigated the immune response against the 76-9 experimental lung metastases after CY + IL-15 therapy. Administration of CY + IL-15, but not IL-15 alone, induced prolongation of life and cures in 32% of mice bearing established experimental pulmonary metastases of 76-9 tumor. The CY + IL-15 therapy resulted in increased levels of NK1.1+/LGL-1+ cells, and CD8+/CD44+ T cells in PBL. In vitro cytotoxic assay of PBL indicated the induction of lymphokine-activated killer cell activity, but no evident tumor-specific class I-restricted lytic activity. Survival studies showed that the presence of NK and T lymphocytes is necessary for successful CY + IL-15 therapy. Experiments using knockout mice implied that either alphabeta or gammadelta T cells were required for an antitumor effect induced by CY + IL-15 therapy. However, mice lacking in both alphabeta and gammadelta T cells failed to respond to combination therapy. Cured B6 and alphabeta or gammadelta T cell-deficient mice were immune to rechallenge with 76-9, but not B16LM tumor. B cell-deficient mice showed a significant improvement in the survival rate both after CY and combination CY + IL-15 therapy compared with normal B6 mice. Overall, the data suggest that the interaction of NK cells with tumor-specific alphabeta or gammadelta T lymphocytes is necessary for successful therapy, while B cells appear to suppress the antitumor effects of CY + IL-15 therapy.

  8. IL-4 and IL-15 promotion of virtual memory CD8(+) T cells is determined by genetic background.

    PubMed

    Tripathi, Pulak; Morris, Suzanne C; Perkins, Charles; Sholl, Allyson; Finkelman, Fred D; Hildeman, David A

    2016-10-01

    Virtual memory (VM) CD8(+) T cells are present in unimmunized mice, yet possess T-cell receptors specific for foreign antigens. To date, VM cells have only been characterized in C57BL/6 mice. Here, we assessed the cytokine requirements for VM cells in C57BL/6 and BALB/c mice. As reported previously, VM cells in C57BL/6 mice rely mostly on IL-15 and marginally on IL-4. In stark contrast, VM cells in BALB/c mice rely substantially on IL-4 and marginally on IL-15. Further, NKT cells are the likely source of IL-4, because CD1d-deficient mice on a BALB/c background have significantly fewer VM cells. Notably, this NKT/IL-4 axis contributes to appropriate effector and memory T-cell responses to infection in BALB/c mice, but not in C57BL/6 mice. However, the effects of IL-4 are manifest prior to, rather than during, infection. Thus, cytokine-mediated control of the precursor population affects the development of virus-specific CD8(+) T-cell memory. Depending upon the genetic background, different cytokines encountered before infection may influence the subsequent ability to mount primary and memory anti-viral CD8(+) T-cell responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. IL-15 inhibits pre-B cell proliferation by selectively expanding Mac-1{sup +}B220{sup +} NK cells

    SciTech Connect

    Nakajima, Shinsuke; Hida, Shigeaki; Taki, Shinsuke

    2008-05-16

    Natural killer (NK) cells are the cells critical for inhibition of repopulation of allogenic bone marrow cells. However, it is not well known if NK cells affect autologous lymphopoiesis. Here, we observed that NK cells could inhibit pre-B cell proliferation in vitro driven by interleukin (IL)-7 in a manner dependent on IL-15. Interestingly, the great majority of expanding NK cells were Mac-1{sup +}B220{sup +}, a recently identified potent interferon (IFN)-{gamma} producer. Indeed, IFN-{gamma} was produced in those cultures, and pre-B cells lacking IFN-{gamma} receptors, but not those lacking type I IFN receptors, were resistant to such an inhibition. Furthermore, even NK cells from mice lacking {beta}2-microglobulin, which were known to be functionally dampened, inhibited pre-B cell proliferation as well. Thus, activated NK cells, which were expanded selectively by IL-15, could potentially regulate B lymphopoiesis through IFN-{gamma} beyond the selection imposed upon self-recognition.

  10. Soluble γc cytokine receptor suppresses IL-15 signaling and impairs iNKT cell development in the thymus

    PubMed Central

    Park, Joo-Young; Jo, Yuna; Ko, Eunhee; Luckey, Megan A.; Park, Yoo Kyoung; Park, Se-Ho; Park, Jung-Hyun; Hong, Changwan

    2016-01-01

    The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4+CD8+ thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis. Notably, sγc overexpression also impaired generation of iNKT cells, resulting in reduced iNKT cell percentages and numbers in the thymus. iNKT cell development requires IL-15, and we found that sγc interfered with IL-15 signaling to suppress iNKT cell generation in the thymus. Thus, sγc represents a new mechanism to control cytokine availability during T cell development that constrains mature T cell production and specifically iNKT cell generation in the thymus. PMID:27833166

  11. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells

    PubMed Central

    Mao, Yumeng; van Hoef, Vincent; Zhang, Xiaonan; Wennerberg, Erik; Lorent, Julie; Witt, Kristina; Masvidal, Laia; Liang, Shuo; Murray, Shannon; Larsson, Ola; Kiessling, Rolf

    2016-01-01

    Treatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor postinfusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK-cell functions following cytokine withdrawal to model postinfusion performance. In contrast to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided cell function advantages. Genome-wide analysis of cytosolic and polysome-associated messenger RNA (mRNA) revealed not only cytokine-dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mammalian target of rapamycin (mTOR) signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15–induced cell function advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK-cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15–stimulated NK cells was also observed using a clinically applicable protocol for NK-cell expansion in vitro and in vivo. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B-cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR-regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy. PMID:27465917

  12. Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα.

    PubMed

    Dijkstra, Johannes M; Takizawa, Fumio; Fischer, Uwe; Friedrich, Maik; Soto-Lampe, Veronica; Lefèvre, Christophe; Lenk, Matthias; Karger, Axel; Matsui, Taei; Hashimoto, Keiichiro

    2014-02-01

    Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine.

  13. Effect of IL15 rs10833 and SCARB1 rs10846744 on virologic responses in chronic hepatitis C patients treated with pegylated interferon-α and ribavirin.

    PubMed

    Sadeghi, Sahar; Davari, Mehdi; Asli, Esmaeil; Gharibzadeh, Safoora; Vaziri, Farzam; Jamnani, Fatemeh Rahimi; Fateh, Abolfazl; Siadat, Seyed Davar

    2017-09-30

    The scavenger receptor type B class I (SCARBI) is known to be involved in the entry of hepatitis C virus (HCV) into the host, while interleukin-15 (IL15) is an important cytokine in both the innate and acquired immune responses against HCV infection. We investigated the association of IL15 rs10833 or SCARB1 rs10846744 polymorphisms with treatment responses in patients with chronic HCV (CHC). SCARB1 rs10846744 and IL15 rs10833 were identified in 365 treatment-naïve CHC patients through genotyping by TaqMan® Real-Time PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Of these 365 CHC treatment-naïve patients, rapid virological response (RVR), complete early virological response (cEVR), and sustained virological response (SVR) were observed in 53.2%, 76.4%, and 66.0% of the patients, respectively. Multivariate logistic regression analysis revealed that RVR was associated with sex (P=0.016), aspartate aminotransferase (AST) (P=0.026), IL15 rs10833 (AA) genotype (P<0.001), and SCARB1 rs10846744 (CC) genotype (P<0.001), while there was a relationship between alanine aminotransferase (ALT) (P=0.013) and IL15 rs10833 (AA) genotype (P<0.001) with cEVR. Age (<40years) (P=0.001), AST (P=0.029), ALP (P=0.028), HCV genotypes (P=0.005), HCV viral load (P=0.026), IL15 rs10833 (AA) genotype (P<0.001), and SCARB1 rs10846744 (CC) genotype (P=0.001) were strongly associated with SVR. In conclusion, the SCARB1 rs10846744 (CC) and IL15 rs10833 (AA) genotypes can be considered as powerful predictors of treatment responses in CHC patients treated with an interferon-based therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Conditional sterility in plants

    DOEpatents

    Meagher, Richard B.; McKinney, Elizabeth; Kim, Tehryung

    2010-02-23

    The present disclosure provides methods, recombinant DNA molecules, recombinant host cells containing the DNA molecules, and transgenic plant cells, plant tissue and plants which contain and express at least one antisense or interference RNA specific for a thiamine biosynthetic coding sequence or a thiamine binding protein or a thiamine-degrading protein, wherein the RNA or thiamine binding protein is expressed under the regulatory control of a transcription regulatory sequence which directs expression in male and/or female reproductive tissue. These transgenic plants are conditionally sterile; i.e., they are fertile only in the presence of exogenous thiamine. Such plants are especially appropriate for use in the seed industry or in the environment, for example, for use in revegetation of contaminated soils or phytoremediation, especially when those transgenic plants also contain and express one or more chimeric genes which confer resistance to contaminants.

  15. IL-15Rα deficiency in skeletal muscle alters respiratory function and the proteome of mitochondrial subpopulations independent of changes to the mitochondrial genome

    PubMed Central

    O'Connell, Grant C.; Nichols, Cody; Guo, Ge; Croston, Tara L.; Thapa, Dharendra; Hollander, John M.; Pistilli, Emidio E.

    2016-01-01

    Interleukin-15 receptor alpha knockout (IL15RαKO) mice exhibit a greater skeletal muscle mitochondrial density with an altered mitochondrial morphology. However, the mechanism and functional impact of these changes have not been determined. In this study, we characterized the functional, proteomic, and genomic alterations in mitochondrial subpopulations isolated from the skeletal muscles of IL15RαKO mice and B6129 background control mice. State 3 respiration was greater in interfibrillar mitochondria and whole muscle ATP levels were greater in IL15RαKO mice supporting the increases in respiration rate. However, the state 3/state 4 ratio was lower, suggesting some degree of respiratory uncoupling. Proteomic analyses identified several markers independently in mitochondrial subpopulations that are associated with these functional alterations. Next Generation Sequencing of mtDNA revealed a high degree of similarity between the mitochondrial genomes of IL15RαKO mice and controls in terms of copy number, consensus coding and the presence of minor alleles, suggesting that the functional and proteomic alterations we observed occur independent of alterations to the mitochondrial genome. These data provide additional evidence to implicate IL-15Rα as a regulator of skeletal muscle phenotypes through effects on the mitochondrion, and suggest these effects are driven by alterations to the mitochondrial proteome. PMID:26458787

  16. IL-15Rα deficiency in skeletal muscle alters respiratory function and the proteome of mitochondrial subpopulations independent of changes to the mitochondrial genome.

    PubMed

    O'Connell, Grant C; Nichols, Cody; Guo, Ge; Croston, Tara L; Thapa, Dharendra; Hollander, John M; Pistilli, Emidio E

    2015-11-01

    Interleukin-15 receptor alpha knockout (IL15RαKO) mice exhibit a greater skeletal muscle mitochondrial density with an altered mitochondrial morphology. However, the mechanism and functional impact of these changes have not been determined. In this study, we characterized the functional, proteomic, and genomic alterations in mitochondrial subpopulations isolated from the skeletal muscles of IL15RαKO mice and B6129 background control mice. State 3 respiration was greater in interfibrillar mitochondria and whole muscle ATP levels were greater in IL15RαKO mice supporting the increases in respiration rate. However, the state 3/state 4 ratio was lower, suggesting some degree of respiratory uncoupling. Proteomic analyses identified several markers independently in mitochondrial subpopulations that are associated with these functional alterations. Next Generation Sequencing of mtDNA revealed a high degree of similarity between the mitochondrial genomes of IL15RαKO mice and controls in terms of copy number, consensus coding and the presence of minor alleles, suggesting that the functional and proteomic alterations we observed occurred independent of alterations to the mitochondrial genome. These data provide additional evidence to implicate IL-15Rα as a regulator of skeletal muscle phenotypes through effects on the mitochondrion, and suggest these effects are driven by alterations to the mitochondrial proteome.

  17. IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells.

    PubMed

    Shenoy, Aparna R; Kirschnek, Susanne; Häcker, Georg

    2014-08-01

    Maintenance of T cells is determined by their survival capacity, which is regulated by Bcl-2 proteins. Cytokines signalling through the common gamma chains such as IL-2, IL-7 and IL-15 are important for T-cell survival but how these cytokines determine the expression of Bcl-2-family proteins is not clear. We report signalling events of cytokines that regulate expression of two key Bcl-2 proteins, pro-apoptotic Bim and anti-apoptotic Mcl-1, in resting C57BL/6 mouse T cells. IL-2, IL-7 and IL-15 inhibited apoptosis but paradoxically induced the expression of Bim, countered by concomitant induction of Mcl-1. Bim induction by IL-15 was found at the mRNA and protein levels and depended on both JAK/STAT and PI3K signals. A new STAT5-binding site was identified in the Bim promoter, which was occupied by STAT5 upon IL-15 stimulation. Although it also depended on JAK/STAT- and PI3K signalling, Mcl-1 regulation was independent of Mcl-1 mRNA levels and of regulation of protein stability, suggesting translational regulation. Concurrent CD3 signals inhibited some of the IL-7 effect but not the IL-15 effect on Bcl-2 proteins. The data suggest that cytokines induce Bim and prime T cells for apoptosis, but also inhibit apoptosis by stabilising Mcl-1. Later downregulation of short-lived Mcl-1 may induce efficient, Bim-dependent apoptosis.

  18. Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15.

    PubMed

    Litjens, Nicolle H R; Boer, Karin; Zuijderwijk, Joke M; Klepper, Mariska; Peeters, Annemiek M A; Prens, Errol P; Verschoor, Wenda; Kraaijeveld, Rens; Ozgur, Zeliha; van den Hout-van Vroonhoven, Mirjam C; van IJcken, Wilfred F J; Baan, Carla C; Betjes, Michiel G H

    2015-06-01

    Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4(+)CD25(bright)CD127(-) T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR- and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloantigen-induced proliferation without significant suppression of completely HLA-mismatched, Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-γ, and TNF-α, but few IL-17-producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function. Copyright © 2015 by The American Association of Immunologists, Inc.

  19. [Optimal terms for sterilization].

    PubMed

    Ribic-Pucelj, M

    1980-01-01

    Sterilization can be performed in the immediate postpartum, post abortion, or as an interval procedure. Traditionally, postpartum sterilization should be performed within the first two days after delivery, thereafter the risk for infection is believed to increase. Sterilization and artificial abortion are performed as concomitant procedures, while interval sterilization is carried out at least six weeks after the termination of pregnancy. Though many authors consider the sterilization in the immediate postpartum and postabortion period safe enough, the comparative studies show that interval sterilization has less complications. Postpartum (postabortion) sterilization has much more disadvantages than advantages in comparison to interval sterilization. The main advantage of postpartum sterilization is only one hospitalization while disadvantages are the increased risk of hemorrhage, uterine perforation, thromboembolic disease, infection, technical difficulties, and psychological problems. For these reasons interval sterilization is recommended.

  20. Effects of Eccentric and Concentric Emphasized Resistance Exercise on IL-15 Serum Levels and Its Relation to Inflammatory Markers in Athletes and Non-Athletes

    PubMed Central

    Bazgir, Behzad; Salesi, Mohsen; Koushki, Maryam; Amirghofran, Zahra

    2015-01-01

    Background: Cytokines play an important role in modulating the muscle’s metabolic and immunological responses to exercise. Objectives: In the present study, we investigated changes in the serum levels of Interleukin (IL)-15 as well as tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hs-CRP), as markers of inflammation, in athlete and non-athlete young men following eccentric (ECC) and concentric (CON) emphasized resistance exercise (RE). Patients and Methods: This study recruited 28 young males, 14 athletes and 14 non-athletes. Subjects completed two bouts of ECC and CON emphasized RE five days apart. Each bout included seven exercises that emphasized all major muscle groups with weight loads of 70% - 80% of one repetition maximum (1RM) for CON RE and 90% - 100% of 1RM for ECC RE. We analyzed subjects’ blood samples before and immediately after each bout of exercise to determine cytokine and hs-CRP serum levels according to enzyme-linked immunosorbent assay. Results: Statistical analysis showed a significant difference between IL-15 serum levels before and after ECC and CON RE in non-athletes (P = 0.03). In athletes, IL-15 serum level only increased after ECC RE (P = 0.01), which was noted to be the highest degree of change in IL-15 levels in all subjects. For athletes, the hs-CRP levels significantly decreased (P < 0.05). The serum levels of both TNF-α and hs-CRP were also significantly down-regulated after ECC RE in non-athletes. Conclusions: These results indicated that fitness level and RE could modulate circulating levels of IL-15 and suggest the potential anti-inflammatory effects of IL-15 during RE. PMID:26448857

  1. Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants.

    PubMed

    Krenciute, Giedre; Prinzing, Brooke L; Yi, Zhongzhen; Wu, Meng-Fen; Liu, Hao; Dotti, Gianpietro; Balyasnikova, Irina V; Gottschalk, Stephen

    2017-07-01

    Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CAR) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens, such as IL13 receptor subunit α2 (IL13Rα2), HER2, and EGFR variant III (EGFRvIII), have had antitumor activity in preclinical models, early-phase clinical testing has demonstrated limited antiglioma activity. Transgenic expression of IL15 is an appealing strategy to enhance CAR T-cell effector function. We tested this approach in our IL13Rα2-positive glioma model in which limited IL13Rα2-CAR T-cell persistence results in recurrence of antigen-positive gliomas. T cells were genetically modified with retroviral vectors encoding IL13Rα2-CARs or IL15 (IL13Rα2-CAR.IL15 T cells). IL13Rα2-CAR.IL15 T cells recognized glioma cells in an antigen-dependent fashion, had greater proliferative capacity, and produced more cytokines after repeated stimulations in comparison with IL13Rα2-CAR T cells. No autonomous IL13Rα2-CAR.IL15 T-cell proliferation was observed; however, IL15 expression increased IL13Rα2-CAR T-cell viability in the absence of exogenous cytokines or antigen. In vivo, IL13Rα2-CAR.IL15 T cells persisted longer and had greater antiglioma activity than IL13Rα2-CAR T cells, resulting in a survival advantage. Gliomas recurring after 40 days after T-cell injection had downregulated IL13Rα2 expression, indicating that antigen loss variants occur in the setting of improved T-cell persistence. Thus, CAR T cells for GBM should not only be genetically modified to improve their proliferation and persistence, but also to target multiple antigens.Summary: Glioblastoma responds imperfectly to immunotherapy. Transgenic expression of IL15 in T cells expressing CARs improved their proliferative capacity, persistence, and cytokine production. The emergence of antigen loss

  2. Coimmunization with IL-15 plasmid enhances the longevity of CD8 T cells induced by DNA encoding hepatitis B virus core antigen

    PubMed Central

    Zhang, Wei; Dong, Sheng-Fu; Sun, Shu-Hui; Wang, Yuan; Li, Guang-Di; Qu, Di

    2006-01-01

    AIM: To test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for improving the immune responses induced by hepatitis B virus core gene DNA vaccine. METHODS: We used RT-PCR based strategies to develop IL-15 expression constructs. We first confirmed that the gene could be expressed in Escherichia coli due to the poor expression of IL-15. Then the bioactivity of IL-15 plasmid expression product was identified by CTLL-2 proliferation assay. One hundred micrograms of DNA from each of the IL-15 eukaryotic expressed plasmid and the recombinant plasmid harboring DNA encoding the 144 amino acids of the N-terminus of HBV core gene (abbreviated pHBc144) was used to co-immunize C57 BL/6 mice. The titer of anti-HBcIgG was detected by ELISA and the antigen-specific CD8+ T cells (CD8+IFN-γ+ T cells) were detected by intracellular cytokine staining at different time points. RESULTS: After co-immunization by pIL-15 and pHBc144 DNA vaccine the antigen-specific CD8+ cells of mice increased gradually, the first peak of immune response appeared 14 d later, then the number of antigen-specific CD8+ Ts cells decreased gradually and maintained at a steady level in 3 mo. After boosting, the number of antigen-specific CD8+ T cells reached the second peak 10 d later with a double of the 1st peak, then the number of antigen-specific CD8+ T cells decreased slowly. IL-15 as a gene adjuvant had no significant effect on humoral immune responses induced by hepatitis B virus core gene DNA vaccine, but increased the memory antigen-specific CD8+ T cells induced by hepatitis B virus core gene DNA vaccine. CONCLUSION: DNA vaccine constructed by HBc Ag 1-144 amino acid induces effective cell immunity, and cytokine plasmid-delivered IL-15 enhances the longevity of CD8+ T cells. PMID:16937447

  3. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma

    PubMed Central

    Adachi, Takeya; Kobayashi, Tetsuro; Sugihara, Eiji; Yamada, Taketo; Ikuta, Koichi; Pittaluga, Stefania; Saya, Hideyuki; Amagai, Masayuki; Nagao, Keisuke

    2015-01-01

    The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis via chemokine production. We demonstrate that CD4+ and CD8+ skin resident memory T cells (TRM), responsible for long-term skin immunity, resided predominantly within the hair follicle epithelium of unperturbed epidermis. TRM tropism for the epidermis and follicles was herein termed epidermotropism. Hair follicle-derived IL-15 was required for CD8+ TRM, and IL-7 for CD8+ and CD4+ TRM, to exert epidermotropism. The lack of either cytokine impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4+ TRM lymphoma cell localization depended on hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant TRM cell tissue residence and suggest they may be targeted therapeutically in inflammatory skin disease and lymphoma. PMID:26479922

  4. CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7- and IL-15-dependent niches.

    PubMed

    Jung, Yong Woo; Kim, Hyun Gyung; Perry, Curtis J; Kaech, Susan M

    2016-07-19

    C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T-cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7-deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7(-/-) memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7-dependent niches over IL-15-dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets.

  5. PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness

    PubMed Central

    Yang, Meixiang; Li, Dan; Chang, Zai; Yang, Zhongzhou; Tian, Zhigang

    2015-01-01

    E4BP4, a circadian protein, is indispensable for NK cell development. It remains largely unknown which signal is required to induce E4BP4 expression and what effects it has during NK cell differentiation. Here, we reveal that PDK1, a kinase upstream of mTOR, connects IL-15 signaling to E4BP4. Early deletion of PDK1 caused a severe loss of NK cells and compromised antitumor activity in vivo. PDK1-deficient NK cells displayed much weaker IL-15–induced mTOR activation and E4BP4 induction, as well as remarkable reduction in CD122, a receptor subunit specifying NK cell responsiveness to IL-15. The phenotypes were partially reversible by ectopic expression of E4BP4 or bypassed activation of mTOR. We also determined that PDK1-mediated metabolic signaling was dispensable for NK cell terminal maturation and survival. Thus, we identify a role for PDK1 signaling as a key mediator in regulating E4BP4 expression during early NK cell development. Our findings underscore the importance of IL-15 self-responsiveness through a positive feedback loop that involves PDK1–mTOR–E4BP4–CD122 signaling. PMID:25624444

  6. Sterilization of glycerin.

    PubMed

    McCluskey, Susan V

    2008-06-15

    The sterilization of glycerin is described. Glycerin is used in a wide variety of pharmaceutical formulations, including oral, otic, ophthalmic, topical, and parenteral preparations. Of the myriad uses for glycerin, some require a sterile solution. Due to the nature of dry heat sterilization with resulting equipment and validation needs, sterile filtration is the preferred sterilization method for glycerin at the Mayo Clinic Pharmacy Services Production Laboratory in Rochester, Minnesota. A practical procedure was attained with the use of a chemically compatible 0.22-microm capsule filter, peristaltic pump, and sterile tubing. The sterile tubing is attached firmly, with a twisting motion, to the hose barb ends of the filter. The peristaltic pump is set at minimum speed, and a sterile syringe is used to capture the sterile glycerin filtrate. After filtration, filter integrity testing using the bubble point test is performed on the filter used to sterilize the solution. Packaging was then completed by placing glycerin aliquots into unit-of-use sterile syringes, placing a sterile tip cap on each syringe, and labeling the syringe. End testing is needed for preparations, such as sterile glycerin, that are made from nonsterile components, regardless of sterilization technique. This quality-control testing includes but is not limited to visual checks, pH checks, and tests for bacterial endotoxins, particulate matter, and sterility. Beyond-use dating is then assigned based on chemical, physical, microbiological, and packaging considerations. A practical method for sterilization of glycerin by compounding pharmacists is attainable through the use of membrane filtration. Sterility assurance is achieved through appropriate validation, and quality-control checks must be completed before release of the injectable preparation.

  7. Sterilizing the Poor

    ERIC Educational Resources Information Center

    Rothman, Sheila M.

    1977-01-01

    Suggests that freedom for the middle classes may mean vulnerability for the poor. The enthusiasm for sterilization may be so intense as to deprive the poor of their right not to be sterilized. (Author/AM)

  8. [Complications of tubal sterilization].

    PubMed

    Schreiner, W E

    1986-05-01

    In Europe and the US, tubal sterilization by laparoscopy has become the most widely used technique for female sterilization. The overall rate of intra- and postoperative complications differs between 0.145% and 0.85% in the numerous studies which have been done. This means 1 severe complication in 120-700 laparoscopic sterilizations. The lethality of tubal sterilization by laparoscopy lies between 3-10 deaths/100,000 interventions. The so-called "post-tubal ligation syndrome" is a rare complication. The overall pregnancy rate after tubal sterilization is 3-10/1000 women. The rate of ectopic pregnancy is very high and varies between 13.6% and 90%. Only 5% of the sterilized women show dissatisfaction. Several factors are relevant with regard to psychological sequelae and must be considered before tubal sterilization can be performed. 1 of the most important is the individual comprehensive counselling of the female or the couple prior to the sterilization.

  9. Apparatus Circulates Sterilizing Gas

    NASA Technical Reports Server (NTRS)

    Cross, John H.; Schwarz, Ray P.

    1991-01-01

    Apparatus circulates sterilizing gas containing ethylene oxide and chlorofluorocarbon through laboratory or medical equipment. Confines sterilizing gas, circulating it only through parts to be treated. Consists of two units. One delivers ethylene oxide/chlorofluorocarbon gas mixture and removes gas after treatment. Other warms, humidifies, and circulates gas through equipment to be treated. Process provides reliable sterilization with negligible residual toxicity from ethylene oxide. Particularly suitable for sterilization of interiors of bioreactors, heart/lung machines, dialyzers, or other equipment including complicated tubing.

  10. The backcross sterility technique

    Treesearch

    V. C. Mastro; A. Pellegrini-Toole

    1991-01-01

    The sterile insect technique (SIT) and the induced inherited (F1) sterility technique have been investigated for a number of lepidopterous pests, including the gypsy moths. Another technique, backcross sterility, which could potentially prove as or more useful for control of pest species has been developed for the control of only one lepidopteran...

  11. Plasma-Based Sterilization

    DTIC Science & Technology

    2003-07-20

    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP014940 TITLE: Plasma-Based Sterilization DISTRIBUTION: Approved for...compilation report: ADP014936 thru ADP015049 UNCLASSIFIED Plasma-Based Sterilization Mounir Laroussi Electrical & Computer Engineering Department Old...Dominion University Norfolk, VA 23529 Rapid, safe, and effective sterilization is of the utmost importance when it comes to protecting the public in

  12. Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

    PubMed Central

    Sullivan, Nicole L.; Blazevic, Azra; Bruna-Romero, Oscar; Rodrigues, Mauricio M.; Hoft, Daniel F.

    2011-01-01

    Background Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone. Methodology We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization. The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05). Improved protection correlated with significantly higher numbers of TS-specific IFN-γ producing total and CD8+ T cells detected>6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro re-stimulation. Conclusion Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi. PMID:21408124

  13. Antibody and T cell responses induced in chickens immunized with avian influenza virus N1 and NP DNA vaccine with chicken IL-15 and IL-18.

    PubMed

    Lim, Kian-Lam; Jazayeri, Seyed Davoud; Yeap, Swee Keong; Mohamed Alitheen, Noorjahan Banu; Bejo, Mohd Hair; Ideris, Aini; Omar, Abdul Rahman

    2013-12-01

    We had examined the immunogenicity of a series of plasmid DNAs which include neuraminidase (NA) and nucleoprotein (NP) genes from avian influenza virus (AIV). The interleukin-15 (IL-15) and interleukin-18 (IL-18) as genetic adjuvants were used for immunization in combination with the N1 and NP AIV genes. In the first trial, 8 groups of chickens were established with 10 specific-pathogen-free (SPF) chickens per group while, in the second trial 7 SPF chickens per group were used. The overall N1 enzyme-linked immunosorbent assay (ELISA) titer in chickens immunized with the pDis/N1+pDis/IL-15 was higher compared to the chickens immunized with the pDis/N1 and this suggesting that chicken IL-15 could play a role in enhancing the humoral immune response. Besides that, the chickens that were immunized at 14-day-old (Trial 2) showed a higher N1 antibody titer compared to the chickens that were immunized at 1-day-old (Trial 1). Despite the delayed in NP antibody responses, the chickens co-administrated with IL-15 were able to induce earlier and higher antibody response compared to the pDis/NP and pDis/NP+pDis/IL-18 inoculated groups. The pDis/N1+pDis/IL-15 inoculated chickens also induced higher CD8+ T cells increase than the pDis/N1 group in both trials (P<0.05). The flow cytometry results from both trials demonstrated that the pDis/N1+pDis/IL-18 groups were able to induce CD4+ T cells higher than the pDis/N1 group (P<0.05). Meanwhile, pDis/N1+pDis/IL-18 group was able to induce CD8+ T cells higher than the pDis/N1 group (P<0.05) in Trial 2 only. In the present study, pDis/NP was not significant (P>0.05) in inducing CD4+ and CD8+ T cells when co-administered with the pDis/IL-18 in both trials in comparison to the pDis/NP. Our data suggest that the pDis/N1+pDis/IL-15 combination has the potential to be used as a DNA vaccine against AIV in chickens.

  14. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene.

    PubMed

    Hsu, Cary; Jones, Stephanie A; Cohen, Cyrille J; Zheng, Zhili; Kerstann, Keith; Zhou, Juhua; Robbins, Paul F; Peng, Peter D; Shen, Xinglei; Gomes, Theotonius J; Dunbar, Cynthia E; Munroe, David J; Stewart, Claudia; Cornetta, Kenneth; Wangsa, Danny; Ried, Thomas; Rosenberg, Steven A; Morgan, Richard A

    2007-06-15

    Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8(+) T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus-based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28(-), CD45RA(-), CD45RO(+), and CD62L(-), a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen-specific T-cell receptors, the clone secreted IFN-gamma upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15R alpha expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation.

  15. Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2.

    PubMed

    Bai, Yang; Xu, Rui; Zhang, Xueyuan; Zhang, Xiaorong; Hu, Xiaohong; Li, Yashu; Li, Haisheng; Liu, Meixi; Huang, Zhenggen; Yan, Rongshuai; He, Weifeng; Luo, Gaoxing; Wu, Jun

    2017-07-26

    Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent. © 2017 The Author(s). Published by S. Karger AG, Basel.

  16. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene

    PubMed Central

    Hsu, Cary; Jones, Stephanie A.; Cohen, Cyrille J.; Zheng, Zhili; Kerstann, Keith; Zhou, Juhua; Robbins, Paul F.; Peng, Peter D.; Shen, Xinglei; Gomes, Theotonius J.; Dunbar, Cynthia E.; Munroe, David J.; Stewart, Claudia; Cornetta, Kenneth; Wangsa, Danny; Ried, Thomas; Rosenberg, Steven A.

    2007-01-01

    Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8+ T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus–based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28−, CD45RA−, CD45RO+, and CD62L−, a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen–specific T-cell receptors, the clone secreted IFN-γ upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15Rα expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation. PMID:17353346

  17. Dendritic cell secretion of IL-15 is induced by recombinant huCD40LT and augments the stimulation of antigen-specific cytolytic T cells.

    PubMed

    Kuniyoshi, J S; Kuniyoshi, C J; Lim, A M; Wang, F Y; Bade, E R; Lau, R; Thomas, E K; Weber, J S

    1999-04-10

    Dendritic cells (DC) are professional antigen-presenting cells which stimulate strong proliferative and cytolytic T cell responses. Stimulation of CD40 on dendritic cells by its ligands and anti-CD40 antibodies induces maturation and enhances DC stimulatory ability. In order to understand the mechanism by which ligand:CD40 interactions augment DC function, we assessed the role of T cell stimulatory cytokines IL-12 and IL-15 in the function of DC stimulated with soluble trimeric CD40L, a recombinant fusion protein incorporating three covalently linked extracellular CD40L domains (huCD40LT). Peripheral blood derived DC treated with huCD40LT and/or IFN-gamma were used to stimulate T cell responses in vitro to specific antigens. DC treated with huCD40LT or IFN-gamma/huCD40LT stimulated enhanced T cell proliferation to CASTA, a soluble protein from C. albicans, induced T cells with augmented antigen-specific lysis, and increased the yield of antigen-specific IFN-gamma-producing T cells. IL-15 production by DC was enhanced in cultures treated with huCD40LT and correlated with expansion of antigen-specific cytolytic T cells. Addition of a neutralizing anti-IL-15 monoclonal antibody inhibited the expansion of viral and tumor antigen-specific T cells stimulated by IFN-gamma and huCD40LT-treated DC. In contrast, this enhanced stimulatory ability of DC did not appear to depend on synthesis of IL-12 since huCD40LT treatment stimulated the generation of antigen-specific cytokine producing and cytolytic T cells without increased IL-12 production. Addition of anti-IL-12 monoclonal antibody did not inhibit expansion of these cells. These data suggest that production of IL-15 but not IL-12 is an important factor in the enhanced immunostimulatory ability of huCD40LT-treated DC.

  18. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell–depleted stem cell transplantation

    PubMed Central

    Shah, Nirali N.; Baird, Kristin; Delbrook, Cynthia P.; Fleisher, Thomas A.; Kohler, Mark E.; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K.; Kleiner, David E.; Merchant, Melinda S.; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F.; Wayne, Alan S.; Zhang, Hua; Fry, Terry J.

    2015-01-01

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL–activated NK cells (aNK-DLI) following HLA-matched, T-cell–depleted (1-2 × 104 T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3+-depleted, CD56+-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL+IL-15Rα+ artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104. PMID:25452614

  19. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model.

    PubMed

    Mathios, Dimitrios; Park, Chul-Kee; Marcus, Warren D; Alter, Sarah; Rhode, Peter R; Jeng, Emily K; Wong, Hing C; Pardoll, Drew M; Lim, Michael

    2016-01-01

    Glioblastoma is the most aggressive primary central nervous system malignancy with a poor prognosis in patients. Despite the need for better treatments against glioblastoma, very little progress has been made in discovering new therapies that exhibit superior survival benefit than the standard of care. Immunotherapy has been shown to be a promising treatment modality that could help improve clinical outcomes of glioblastoma patients by assisting the immune system to overcome the immunosuppressive tumor environment. Interleukin-15 (IL-15), a cytokine shown to activate several effector components of the immune system, may serve as an excellent immunotherapeutic candidate for the treatment of glioblastoma. Thus, we evaluated the efficacy of an IL-15 superagonist complex (IL-15N72D:IL-15RαSu-Fc; also known as ALT-803) in a murine GL261-luc glioblastoma model. We show that ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice. In addition, ALT-803 treatment results in long-term immune memory against glioblastoma tumor rechallenge. Flow cytometric analysis of tumor infiltrating immune cells shows that ALT-803 leads to increased percentage of CD8+-cell infiltration, but not the NK cells, and IFN-γ production into the tumor microenvironment. Cell depletion studies, in accordance with the flow cytometric results, show that the ALT-803 therapeutic effect is dependent on CD4+ and CD8+ cells. These results provide a rationale for evaluating the therapeutic activity of ALT-803 against glioblastoma in the clinical setting.

  20. Coimmunization with an optimized IL15 plasmid adjuvant enhances humoral immunity via stimulating B cells induced by genetically engineered DNA vaccines expressing consensus JEV and WNV E DIII.

    PubMed

    Ramanathan, Mathura P; Kutzler, Michele A; Kuo, Yuan-Chia; Yan, Jian; Liu, Harrison; Shah, Vidhi; Bawa, Amrit; Selling, Bernard; Sardesai, Niranjan Y; Kim, J Joseph; Weiner, David B

    2009-07-09

    The Japanese encephalitis virus (JEV) and West Nile virus (WNV) are responsible for a large proportion of viral encephalitis in humans. Currently, there is no FDA approved specific treatment for either, though there are attempts to develop vaccines against both viruses. In this study, we proposed novel genetically engineered DNA vaccines against these two neurotrophic flaviviruses. The structural domain III (DIII) of E protein from these viruses is reported to carry dominant epitopes that induce neutralizing antibodies. Therefore we created consensus sequence of DIII domain across numerous strains of JEV and WNV. Based on the consensus amino acid sequence, synthetic codon and RNA optimized DIII-expressing DNA vaccine constructs with an efficient leader sequence were synthesized for immunization studies. In addition, we also constructed a genetically engineered IL15 DNA vaccine molecular adjuvant for co-stimulating the immune response against DIII clones. Vaccine constructs were delivered into BALB/C mice intramuscularly followed by electroporation using the CELLECTRA in vivo electroporator. We have observed that the combined delivery of both WNV DIII and IL15-ECRO DNA vaccine constructs resulted in not only the highest level of antibody against DIII, but also enhanced cross reactivity with two other antigens tested. Also, coimmunization with IL15 plasmid further increased the immune response by four- to five-fold. Importantly, we have shown that IL15 coimmunization adjuvanted humoral responses against DIII antigens by elevating the level of antibody secreting B cells. Such a DNA vaccine approach may better help to control potential travel related infectious agents such as JEV.

  1. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation.

    PubMed

    Shah, Nirali N; Baird, Kristin; Delbrook, Cynthia P; Fleisher, Thomas A; Kohler, Mark E; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K; Kleiner, David E; Merchant, Melinda S; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F; Wayne, Alan S; Zhang, Hua; Fry, Terry J; Mackall, Crystal L

    2015-01-29

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 × 10(4) T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+)IL-15Rα(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104.

  2. Sterilization of endoscopic instruments.

    PubMed

    Sabnis, Ravindra B; Bhattu, Amit; Vijaykumar, Mohankumar

    2014-03-01

    Sterilization of endoscopic instruments is an important but often ignored topic. The purpose of this article is to review the current literature on the sterilization of endoscopic instruments and elaborate on the appropriate sterilization practices. Autoclaving is an economic and excellent method of sterilizing the instruments that are not heat sensitive. Heat sensitive instruments may get damaged with hot sterilization methods. Several new endoscopic instruments such as flexible ureteroscopes, chip on tip endoscopes, are added in urologists armamentarium. Many of these instruments are heat sensitive and hence alternative efficacious methods of sterilization are necessary. Although ethylene oxide and hydrogen peroxide are excellent methods of sterilization, they have some drawbacks. Gamma irradiation is mainly for disposable items. Various chemical agents are widely used even though they achieve high-level disinfection rather than sterilization. This article reviews various methods of endoscopic instrument sterilization with their advantages and drawbacks. If appropriate sterilization methods are adopted, then it not only will protect patients from procedure-related infections but prevent hypersensitive allergic reactions. It will also protect instruments from damage and increase its longevity.

  3. IL-15 enhances the anti-tumor activity of trastuzumab against breast cancer cells but causes fatal side effects in humanized tumor mice (HTM)

    PubMed Central

    Wege, Anja K; Weber, Florian; Kroemer, Alexander; Ortmann, Olaf; Nimmerjahn, Falk; Brockhoff, Gero

    2017-01-01

    Cancer immunotherapy has been shown to enhance established treatment regimens. We evaluated the potential reinforcing effect of IL-15 in trastuzumab treated humanized tumor mice (HTM) which were generated by concurrent transplantation of neonatal NOD-scid IL2Rγnull mice with human hematopoietic stem cells (HSC) and HER2 positive breast cancer cells (metastasizing SK-BR-3, solid tumor forming BT474). We found that trastuzumab treatment efficacy mainly depends on the immediate anti-tumorigenic cellular effect which is significantly enhanced by tumor interacting immune cells upon cotransplantion of HSC. However, trastuzumab treatment caused elevated CD44 expression on tumor cells that metastasized into the lung and liver but did not hinder tumor cell dissemination into the bone marrow. Moreover, in a number of SK-BR-3-transplanted animals disseminated CD44high/CD24low tumor cells lost trastuzumab sensitivity. Concerning the FcγRIIIa polymorphism, trastuzumab treatment efficiency in HTM was higher in mice with NK-cells harboring the high affinity FcγRIIIa compared to those with low affinity FcγRIIIa. In contrast, IL-15 caused the strongest NK-cell activation in heterozygous low affinity FcγRIIIa animals. Although IL-15 enhanced the trastuzumab mediated tumor defense, an unspecific immune stimulation resulted in preterm animal death due to systemic inflammation. Overall, treatment studies based on “patient-like” HTM revealed critical and adverse immune-related mechanisms which must be managed prior to clinical testing. PMID:27835865

  4. T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate.

    PubMed

    Mackay, Laura K; Wynne-Jones, Erica; Freestone, David; Pellicci, Daniel G; Mielke, Lisa A; Newman, Dane M; Braun, Asolina; Masson, Frederick; Kallies, Axel; Belz, Gabrielle T; Carbone, Francis R

    2015-12-15

    Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling. TGF-β signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor β-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-β and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.

  5. Construction of a plasmid for co-expression of mouse membrane-bound form of IL-15 and RAE-1ε and its biological activity.

    PubMed

    Qian, Li; Ji, Ming-Chun; Pan, Xin-Yuan; Gong, Wei-Juan; Tian, Fang; Duan, Qiu-Fang

    2011-05-01

    Interleukin 15 (IL-15) is a pivotal cytokine for the proliferation and activation of a specific group of immune cells such as natural killer (NK), IFN-producing killer dendritic cells (IKDC) and CD8 T cells. RAE-1ε, the ligand for the activating NKG2D receptor, which also play an important role in the proliferation and activation of NK cells and IKDCs. In this study, a membrane-bound form of IL-15 (termed mb15) encoding sequence and RAE-1ε gene were obtained by SOE-PCR or PCR amplification. The amplified mb15 and RAE-1ε gene were then digested and inserted into the multiple cloning site1 (MCS1) and MCS2 of pVITRO2-mcs vector, respectively. A recombinant eukaryotic expression vector for co-expression of mb15 and RAE-1ε was successfully constructed. After it was transfected to BaF3 cells, the expression of IL-15 and RAE-1ε in recombinant BaF3/mb15/RAE-1ε cells were verified by RT-PCR, western blot and FCM analysis. Furthermore, BaF3/mb15/RAE-1ε cells had the ability of promoting NK cells proliferation and IFN-γ secretion. In conclusion, BaF3/mb15/RAE-1ε cells were successfully constructed, which is very useful for further studies, especially for the expansion and activation of certain subsets of immune cells such as NK cells and IKDCs.

  6. IL-2 and IL-15 Each Mediate De Novo Induction of FOXP3 Expression in Human Tumor Antigen-specific CD8 T Cells

    PubMed Central

    Ahmadzadeh, Mojgan; Antony, Paul A.; Rosenberg, Steven A.

    2007-01-01

    Summary Although FOXP3 is primarily expressed by regulatory CD4 T cells (Treg) in vivo, polyclonal activation of human CD8 T cells can result in the expression of FOXP3 in a fraction of CD8 T cells. However, the cellular lineage and mechanism of FOXP3 induction in CD8 T cells remain unclear. Here, we demonstrate that interleukin-2 (IL-2) induces FOXP3 expression in OKT3-stimulated or antigen-stimulated CD8 T cells, indicating that FOXP3 expression is neither limited to a unique subset of CD8 T cells nor dependent on the mode of T-cell receptor stimulation. In the absence of IL-2, antigen stimulation resulted in T-cell activation and acquisition of effector function without induction of FOXP3, indicating that acquisition of effector function is independent of induction of FOXP3 expression in CD8 T cells. Interestingly, IL-15, but not IL-7 or IL-21, also led to de novo induction of FOXP3 in antigen-specific CD8 T cells, suggesting that signaling by IL-2/IL-15Rβ chain is pivotal for induction of FOXP3 in human CD8 T cells. These findings indicate that induction of FOXP3 is intrinsic to CD8 T cells that are activated in the presence of IL-2 or IL-15, and in vitro-induced expression of FOXP3 cannot be simply interpreted as an indicator of Treg activity or activation marker. PMID:17414320

  7. [Sterilization of women].

    PubMed

    Hirsch, H A

    1984-09-01

    Voluntary sterilization is a permanent method of contraception. Therefore medical counseling of patients desiring sterilization is of utmost importance and should include documented incidence of failure (i.e., pregancy), complication risks, and if necessary, the various factors influencing successful reversal, although it should be emphasized that reversal can never be guaranteed. Laproscopic sterilization has proven very successful. Comparison of the advantages and disadvantages of the most used methods appears in Table 7. The most commonly used method is bipolar electrocoagulation in the isthmic tubal section. Unipolar electrocoagulation should not be used. Hysterectomy is too major an operation to be used solely for sterilization purposes, and is indicated only when other procedures have been eliminated. Pregnancy in failed sterilizations is approximately 8-10/1000 using the current methods, and an overwhelming number of these pregnancies are extrauterine. The rate of complications is lowest in laparoscopic interval sterilizations using local anesthesia. Approximately 1% of sterilized women desired reversal, despite preoperative counseling. The success rate of reversal is most favorable when the sterilization was perfomed in the isthmic tubal section with little destruction of tissue (by the clip method), the tubal segments are long, and the time since sterilization is less than 5 years. Reversal is not possible after fimbriectomy.

  8. Sterilization. Disciplined microbial control.

    PubMed

    Miller, C H

    1991-04-01

    The goal of instrument processing is to protect patients by preventing cross-contamination from instruments. The processing involves a series of sequential steps aimed at removing and killing microbes on contaminated instruments and maintaining those instruments in an aseptic state until they are reused. These steps must be conducted carefully to assure success and to reduce chances of disease spread or physical injury to those handling the contaminated instruments. Presoaking begins the cleaning process and facilitates terminal cleaning by ultrasonic or manual scrubbing. If instruments are not properly cleaned, subsequent sterilization may be jeopardized by insulation of blood- or saliva-coated microbes from the sterilizing agent. Items that would be destroyed by heat should be cleaned and sterilized in a properly prepared glutaraldehyde solution. Cleaned instruments must be packaged prior to heat sterilization to protect them from recontamination after sterilization and before reuse. Sterilization of cleaned, packaged instruments in steam, chemical vapor, or dry heat sterilizers must involve proper loading, processing, drying, and cooling. Routine use of spore tests and chemical indicators will provide quality assessment of packaging procedures and operation of the sterilizer, as well as assist in identifying processed packages during distribution. Using the results of sterilization monitoring to adjust procedures as a means of assuring sterilization provides quality assurance to the office staff and to the patients that the instruments have been properly processed. Carefully handling storage and distribution of the sterilized instrument packs or trays reduces the chances for recontamination until the instruments are reused. Instrument processing is a major part of the office infection control program. It must be performed in a controlled manner with proper monitoring to achieve the desired outcome of patient protection.

  9. The IL-15-based ALT-803 complex enhances FcγRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas

    PubMed Central

    Rosario, Maximillian; Bai, Liu; Kong, Lin; Collins, Lynne I.; Schneider, Stephanie E.; Chen, Xiaoyue; Han, Kaiping; Jeng, Emily K.; Rhode, Peter R.; Leong, Jeffrey W.; Schappe, Timothy; Jewell, Brea A.; Keppel, Catherine R.; Shah, Keval; Hess, Brian; Romee, Rizwan; Piwnica-Worms, David R.; Cashen, Amanda F.; Bartlett, Nancy L.; Wong, Hing C.; Fehniger, Todd A.

    2015-01-01

    PURPOSE Anti-CD20 monoclonal antibodies (mAbs) are an important immunotherapy for B cell lymphoma, and provide evidence that the immune system may be harnessed as an effective lymphoma treatment approach. ALT-803 is a super-agonist IL-15 mutant and IL-15Rα–Fc fusion complex that activates the IL-15 receptor constitutively expressed on NK cells. We hypothesized that ALT-803 would enhance anti-CD20 mAb-directed NK cell responses and antibody-dependent cellular cytotoxicity (ADCC). EXPERIMENTAL DESIGN We tested this hypothesis by adding ALT-803 immunostimulation to anti-CD20 mAb triggering of NK cells in vitro and in vivo. Cell lines and primary human lymphoma cells were utilized as targets for primary human NK cells. Two complementary in vivo mouse models were used, which included human NK cell xenografts in NOD-SCID-γc−/− mice. REULTS We demonstrate that short-term ALT-803 stimulation significantly increased degranulation, IFN-γ production, and ADCC by human NK cells against B-cell lymphoma cell lines or primary follicular lymphoma cells. ALT-803 augmented cytotoxicity and the expression of granzyme B and perforin, providing one potential mechanism for this enhanced functionality. Moreover, in two distinct in vivo B cell lymphoma models, the addition of ALT-803 to anti-CD20 mAb therapy resulted in significantly reduced tumor cell burden and increased survival. Long-term ALT-803 stimulation of human NK cells induced proliferation and NK cell subset changes with preserved ADCC. CONCLUSIONS ALT-803 represents a novel immunostimulatory drug that enhances NK cell anti-lymphoma responses in vitro and in vivo, thereby supporting the clinical investigation of ALT-803 plus anti-CD20 mAbs in patients with indolent B cell lymphoma. PMID:26423796

  10. Mouse fetal and embryonic liver cells differentiate human umbilical cord blood (UCB) progenitors into CD56 negative NK cell precursors in the absence of IL-15

    PubMed Central

    McCullar, Valarie; Oostendorp, Robert; Panoskaltsis-Mortari, Angela; Yung, Gong; Lutz, Charles T.; Wagner, John E.; Miller, Jeffrey S.

    2008-01-01

    Objective Human NK cell maturation involves the orderly acquisition of NK cell receptors. Our aim was to understand how stromal interactions and cytokines are important in this developmental process. Methods Human UCB CD34+/Lin−/CD38− cells were cultured on two murine stromal cell lines (AFT024 and EL08-1D2) in a switch culture to study NK cell development. Results When human progenitors were cultured on AFT024 with IL-3 and Flt3-L in the absence of IL-15, NK cell differentiation occurred, albeit at low frequency. These conditions favored the accumulation of CD56− NK cell precursors (CD34+CD7−, CD34+CD7+ and CD34−CD7+ cells), which are populations rare in adult blood but abundant in fresh UCB. In secondary culture, addition of IL-3 or IL-3+Flt3L to IL-15 increased the absolute number of CD56+ NK cells from precursors and the acquisition of CD94 and KIR. To further explore the microenvironment in early NK cell maturation, a cell line derived from murine embryonic liver (EL08-1D2) was studied. NK cell development and KIR acquisition was superior with EL08-1D2 which supported the differentiation of NK cell precursors, NK cell commitment, and proliferation. Conclusion Although the earliest events in NK cell maturation do not require exogenous human IL-15, it is required at a later stage of NK cell commitment. At a minimum, murine stroma, IL-3, and Flt3-L are required to recapitulate early NK cell development and differentiation into distinct NK cell precursors. EL08-1D2 induces KIR acquisition suggesting that extrinsic signals in NK cell development are conserved between mouse and man. PMID:18295962

  11. Induction of protective immune responses against NXS2 neuroblastoma challenge in mice by immunotherapy with GD2 mimotope vaccine and IL-15 and IL-21 gene delivery.

    PubMed

    Kowalczyk, Aleksandra; Wierzbicki, Andrzej; Gil, Margaret; Bambach, Barbara; Kaneko, Yutaro; Rokita, Hanna; Repasky, Elizabeth; Fenstermaker, Robert; Brecher, Martin; Ciesielski, Michael; Kozbor, Danuta

    2007-09-01

    The GD2 ganglioside expressed on neuroectodermal tumor cells is weakly immunogenic in tumor-bearing patients and induces predominantly IgM antibody responses in the immunized host. Using a syngeneic mouse challenge model with GD2-expressing NXS2 neuroblastoma, we investigated novel strategies for augmenting the effector function of GD2-specific antibody responses induced by a mimotope vaccine. We demonstrated that immunization of A/J mice with DNA vaccine expressing the 47-LDA mimotope of GD2 in combination with IL-15 and IL-21 genes enhanced the induction of GD2 cross-reactive IgG2 antibody responses that exhibited cytolytic activity against NXS2 cells. The combined immunization regimen delivered 1 day after tumor challenge inhibited subcutaneous (s.c.) growth of NXS2 neuroblastoma in A/J mice. The vaccine efficacy was reduced after depletion of NK cells as well as CD4(+) and CD8(+) T lymphocytes suggesting involvement of innate and adaptive immune responses in mediating the antitumor activity in vivo. CD8(+) T cells isolated from the immunized and cured mice were cytotoxic against syngeneic neuroblastoma cells but not against allogeneic EL4 lymphoma, and exhibited antitumor activity after adoptive transfer in NXS2-challenged mice. We also demonstrated that coimmunization of NXS2-challenged mice with the IL-15 and IL-21 gene combination resulted in enhanced CD8(+) T cell function that was partially independent of CD4(+) T cell help in inhibiting tumor growth. This study is the first demonstration that the mimotope vaccine of a weakly immunogenic carbohydrate antigen in combination with plasmid-derived IL-15 and IL-21 cytokines induces both innate and adaptive arms of the immune system leading to the generation of effective protection against neuroblastoma challenge.

  12. Antitumor effect of interleukin (IL)-12 in the absence of endogenous IFN-gamma: a role for intrinsic tumor immunogenicity and IL-15.

    PubMed

    Gri, Giorgia; Chiodoni, Claudia; Gallo, Elena; Stoppacciaro, Antonella; Liew, Foo Y; Colombo, Mario P

    2002-08-01

    IFN-gamma knockout mice (GKO) rejected C26 colon carcinoma cells transduced to secrete interleukin(IL)-12 but do not reject similarly transduced TSA mammary adenocarcinoma (C26/12 and TSA/12 cells, respectively). To determine whether such difference could be because of a different tumor response to IFN-gamma, we injected BALB/c mice with TSA, C26, and their IL-12-transduced counterparts rendered unresponsive to IFN-gamma by stable transduction of a dominant negative (DN), truncated IFN-gamma receptor alpha chain. TSA/DN and C26/DN showed the same in vivo growth kinetics as parental cells, whereas coexpression of IL-12 induced rejection independent of tumor-cell responsiveness to IFN-gamma. This suggests that the role of IFN-gamma is primarily in activating the host immune response, which appears to depend on the intrinsic immunogenicity of the target tumor. C26 and TSA share a common tumor-associated antigen, yet C26 cells are more immunogenic than TSA. C26/12 expressed 10-fold higher levels of class I MHC molecules and induced higher CTL activity compared with TSA/12 cells in GKO mice. Moreover, whereas in GKO mice the TSA/12 tumor was associated with a greater number of infiltrating T cells, only those infiltrating C26/12 tumor expressed the activation marker OX40. The search for cytokine(s) that might contribute in determining the different T-cell response to these IL-12-transduced tumors in GKO mice revealed a role of IL-15. In situ hybridization showed IL-15 expression in C26/12 but not in TSA/12 tumors. In addition, injection of GKO mice with soluble IL-15 receptor-alpha to block IL-15 expression prevented rejection of C26/12 cells. Together, the results suggest that in the absence of IFN-gamma, IL-12 can exert antitumor activity through alternative mechanisms, depending on the tumor cell type and the availability of cytokines that can replace IFN-gamma in sustaining T-cell functions.

  13. [Sterilization and eugenics].

    PubMed

    Shasha, Shaul M

    2011-04-01

    The term "eugenics" was coined by Francis Galton in 1883 and was defined as the science of the improvement of the human race by better breeding. "Positive eugenics" referred to methods of encouraging the "most fit" to reproduce more often, while "negative eugenics" was related to ways of discouraging or preventing the "less fit" from reproducing by birth control and sterilization. Many western countries adopted eugenics programs including Britain, Canada, Norway, Australia, Switzerland and others. In Sweden more then 62,000 "unfits" were forcibly sterilized. Many states in the U.S.A. had adopted marriage laws with eugenics criteria including forced sterilization. Approximately 64,000 individuals were sterilized. Eugenics considerations also lay behind the adoption of the Immigration Restriction Act of 1924. The Largest plan on eugenics was adopted by the Nazi regime in Germany. Hundreds of thousands of people, who were viewed as being "unfit", were forcibly sterilized by different methods: Surgical sterilization or castration with severe complications and high mortality rates. X-ray irradiation. The method was suggested by Brack, and tested by Schuman using prisoners in Block No. 10 in Auschwitz and Birkenau. Experiments were also performed by Brack on prisoners using the "window method". "Klauberg method"--injection of irritating materials into the uterus. Experiments were conducted using the plant Caladium Seguinum which was believed to have sterilization and castration properties.

  14. Plasma-Aided Sterilization*

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir; Rader, Mark; Dyer, Fred; Dever, Maureen; Alexeff, Igor

    1996-11-01

    The use of plasma as a sterilization agent was known for some time.In this paper we present recent work using atmospheric pressure plasmas to sterilize liquid and solid matter: The plasma can be a glow discharge or a corona discharge. The results show that sterilization occurs with treatment times which vary from a few seconds to a few minutes. The forseen applications of this method are in the medical, pharmaceutical, and food packaging industry. *Work supported in part by The Air Force Office of Scientific Research.

  15. Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural killer cells.

    PubMed

    Boerman, Gerharda H; van Ostaijen-ten Dam, Monique M; Kraal, Kathelijne C J M; Santos, Susy J; Ball, Lynne M; Lankester, Arjan C; Schilham, Marco W; Egeler, R Maarten; van Tol, Maarten J D

    2015-05-01

    Children with advanced stages (relapsed/refractory and stage IV) of rhabdomyosarcoma (RMS) have a poor prognosis despite intensive chemotherapy and autologous stem cell rescue, with 5-year survival rates ranging from 5 to 35 %. Development of new, additional treatment modalities is necessary to improve the survival rate. In this preclinical study, we investigated the potential of resting and cytokine-activated natural killer (NK) cells to lyse RMS cell lines, as well as the pathways involved, to explore the eventual clinical application of (activated) NK cell immunotherapy. RMS cell lines (n = 3 derived from embryonal RMS and n = 2 derived from alveolar RMS) were susceptible to cytolysis mediated by resting NK cells, and this susceptibility was significantly increased using IL-15-activated NK cells. Flow cytometry and cytolytic assays were used to define the activating and inhibitory pathways of NK cells involved in recognizing and lysing RMS cells. NKG2D and DNAM-1 receptor-ligand interactions were essential in cytolysis by resting NK cells, as simultaneous blocking of both pathways resulted in almost complete abrogation of the cytotoxicity. In contrast, combined blocking of DNAM-1 and NKG2D only led to partial reduction of the lytic activity of IL-15-activated NK cells. In this respect, residual lysis was, at least partly, mediated by pathways involving the natural cytotoxicity receptors NKp30 and NKp46. These findings support further exploration of NK cell-based immunotherapy as adjuvant modality in current treatment strategies of RMS.

  16. [Influence of immunoregulatory cytokines (IL-2, IL-7 and IL-15) in vitro upon activation, proliferation and apoptosis of immune memory T-cells].

    PubMed

    Litvinova, L S; Sokhonevich, N A; Gutsol, A A; Kofanova, K A

    2013-01-01

    Under the experimental conditions in vitro the effects of immunoregulatory cytokines (IL-2, IL-7 and IL-15) on the activation, proliferation and apoptosis of different subpopulations of immune memory T-cell (Cd45RO+) were investigated in healthy donors. It was demonstrated that the effects of rlL-2 in vitro equally affect the activation and proliferation of CD4+ and CD8+ subpopulations of memory T cells. It has been shown that high concentrations of rIL-2 lead to an increase in the number of CD8+ memory cells expressing apoptotic molecule CD95. Different effect of rIL-7 and rIL-15 on the activation and proliferation of cytotoxic CD8+ memory ells has been revealed in vitro. CD4+ memory lymphocytes have relative resistance to the activation and proliferative effect of rlL-7 and rlL-15, if compared with the effects of rIL-2, which can provide their relative resistance to the activation apoptosis as well as create the necessary conditions for the accelerated implementation of their functional capacity in the development of a secondary immune response.

  17. Combined IL-15 and IL-12 drives the generation of CD34(+)-derived natural killer cells with superior maturation and alloreactivity potential following adoptive transfer.

    PubMed

    Cany, Jeannette; van der Waart, Anniek B; Spanholtz, Jan; Tordoir, Marleen; Jansen, Joop H; van der Voort, Robbert; Schaap, Nicolaas M; Dolstra, Harry

    2015-07-01

    Adoptive transfer of allogeneic natural killer (NK) cells represents a promising treatment approach against cancer, including acute myeloid leukemia (AML). Previously, we reported a cytokine-based culture method for the generation of NK cell products with high cell number and purity. In this system, CD34(+) hematopoietic progenitor cells (HPC) were expanded and differentiated into NK cells under stroma-free conditions in the presence of IL-15 and IL-2. We show that combining IL-15 with IL-12 drives the generation of more mature and highly functional NK cells. In particular, replacement of IL-2 by IL-12 enhanced the cytolytic activity and IFNγ production of HPC-NK cells toward cultured and primary AML cells in vitro, and improved antileukemic responses in NOD/SCID-IL2Rγnull (NSG) mice bearing human AML cells. Phenotypically, IL-12 increased the frequency of HPC-NK cells expressing NKG2A and killer immunoglobulin-like receptor (KIR), which were more responsive to target cell stimulation. In addition, NK15/12 cell products demonstrated superior maturation potential, resulting in >70% positivity for CD16 and/or KIR within 2 weeks after infusion into NSG mice. We predict that higher functionality and faster in vivo maturation will favor HPC-NK cell alloreactivity toward malignant cells in patients, making this cytokine combination an attractive strategy to generate clinical HPC-NK cell products for cancer adoptive immunotherapy.

  18. Sterilization of space hardware.

    NASA Technical Reports Server (NTRS)

    Pflug, I. J.

    1971-01-01

    Discussion of various techniques of sterilization of space flight hardware using either destructive heating or the action of chemicals. Factors considered in the dry-heat destruction of microorganisms include the effects of microbial water content, temperature, the physicochemical properties of the microorganism and adjacent support, and nature of the surrounding gas atmosphere. Dry-heat destruction rates of microorganisms on the surface, between mated surface areas, or buried in the solid material of space vehicle hardware are reviewed, along with alternative dry-heat sterilization cycles, thermodynamic considerations, and considerations of final sterilization-process design. Discussed sterilization chemicals include ethylene oxide, formaldehyde, methyl bromide, dimethyl sulfoxide, peracetic acid, and beta-propiolactone.

  19. Sterilization of space hardware.

    NASA Technical Reports Server (NTRS)

    Pflug, I. J.

    1971-01-01

    Discussion of various techniques of sterilization of space flight hardware using either destructive heating or the action of chemicals. Factors considered in the dry-heat destruction of microorganisms include the effects of microbial water content, temperature, the physicochemical properties of the microorganism and adjacent support, and nature of the surrounding gas atmosphere. Dry-heat destruction rates of microorganisms on the surface, between mated surface areas, or buried in the solid material of space vehicle hardware are reviewed, along with alternative dry-heat sterilization cycles, thermodynamic considerations, and considerations of final sterilization-process design. Discussed sterilization chemicals include ethylene oxide, formaldehyde, methyl bromide, dimethyl sulfoxide, peracetic acid, and beta-propiolactone.

  20. Female Sterilization (Tubal Ligation)

    MedlinePlus

    ... when you want to have it done. Some women are sterilized right after they have a baby or an abortion, ... videos on Youtube © 1998-2017 | Center for Young Women's Health, Boston Children's Hospital. All rights reserved.

  1. Auditing radiation sterilization facilities

    NASA Astrophysics Data System (ADS)

    Beck, Jeffrey A.

    The diversity of radiation sterilization systems available today places renewed emphasis on the need for thorough Quality Assurance audits of these facilities. Evaluating compliance with Good Manufacturing Practices is an obvious requirement, but an effective audit must also evaluate installation and performance qualification programs (validation_, and process control and monitoring procedures in detail. The present paper describes general standards that radiation sterilization operations should meet in each of these key areas, and provides basic guidance for conducting QA audits of these facilities.

  2. Hysteroscopic Tubal Sterilization

    PubMed Central

    McMartin, K

    2013-01-01

    Background Hysteroscopic tubal sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. The procedures involves non-surgical placement of permanent microinserts into both fallopian tubes. Patients must use alternative contraception for at least 3 months postprocedure until tubal occlusion is confirmed. Compared to tubal ligation, potential advantages of the hysteroscopic procedure are that it can be performed in 10 minutes in an office setting without the use of general or even local anesthesia. Objective The objective of this analysis was to determine the effectiveness and safety of hysteroscopic tubal sterilization compared with tubal ligation for permanent female sterilization. Data Sources A standard systematic literature search was conducted for studies published from January 1, 2008, until December 11, 2012. Review Methods Observational studies, randomized controlled trials (RCTs), systematic reviews and meta-analyses with 1 month or more of follow-up were examined. Outcomes included failure/pregnancy rates, adverse events, and patient satisfaction. Results No RCTs were identified. Two systematic reviews covered 22 observational studies of hysteroscopic sterilization. Only 1 (N = 93) of these 22 studies compared hysteroscopic sterilization to laparoscopic tubal ligation. Two other noncomparative case series not included in the systematic reviews were also identified. In the absence of comparative studies, data on tubal ligation were derived for this analysis from the CREST study, a large, multicentre, prospective, noncomparative observational study in the United States (GRADE low). Overall, hysteroscopic sterilization is associated with lower pregnancy rates and lower complication rates compared to tubal ligation. No deaths have been reported for hysteroscopic sterilization. Limitations A lack of long-term follow-up for hysteroscopic sterilization and a paucity of studies that directly

  3. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL

    PubMed Central

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R.; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-01-01

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07–5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05–3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02–5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28–12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61–28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL. PMID:27427275

  4. The effect of IL-2, IL-12 and IL15 on the function of natural killer cells in children suffering from type 1 diabetes mellitus.

    PubMed

    Chrul, Sławomir; Polakowska, Ewa; Mycko, Marcin; Fendler, Wojciech; Zwiech, Rafał; Szadkowska, Agnieszka

    2013-01-01

    The immunologic reaction of pancreatic islets destruction leads to the occurrence of type 1 diabetes mellitus (T1D). The autoreactive lymphocytes play the pivotal role in this process although mechanisms regulating the lymphocyte migration and infiltration of Langerhans islets have not been fully understood yet. The in vitro studies showed natural killer (NK) cells potency to initiate pancreatic islets cell lyses. Many authors postulate that NK cells may be involved in this reaction. The aim of the study was to evaluate the effect of IL-2, IL-12 and IL-15 stimulation on peripheral blood NK cells in children suffering from type 1 diabetes mellitus in comparison to healthy controls. Fifteen children with type 1 diabetes and 10 healthy adults were examined. NK cells were isolated by the magnetic cell separation system (MACS). For activation, NK cells were cultured with IL-2, IL-12 and IL-15 for 24 hours. The production of IFN-γ and IL-10 by NK cells was measured using commercial ELISA kits. FACS analysis of cell surface antigens--CD16, CD56, NKG2D and CD137 was performed using LSR II flow cytometer. In children with T1D the IFN-γ median concentration in supernatant obtained from NK cells culture was 16.831 ng/ml (inter quartile range 5.566-25.509) and did not statistically differ from median IFN-γ concentration in the control group--14.810 ng/ml (7.022-18.785), p = 0.76. In contrast, the IL-10 median concentration was statistically higher in T1D patients 7.87 pg/ml (1.32-11.37) than in healthy participants--1.41 pg/ml (1.05-4.81), p = 0.01. The median (inter-quartile range) percentage of NK NKG2D(+) was found in 0.42% (0.28-0.76) cells of TID patients versus 0.72% (0.53-1.08) in the controls (p = 0.05). There was no difference between -T1D group and the control group in regard to NK cells expressing CD137 - 6.58% (3.38-12.4) versus 6.85% (2.94-10.8); p = 0.8. The observed activity of NK cells after in vitro stimulation by IL2, IL-12 and IL15 in children suffering

  5. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

    PubMed

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-07-18

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02-5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

  6. Cutting edge: TGF-beta1 and IL-15 Induce FOXP3+ gammadelta regulatory T cells in the presence of antigen stimulation.

    PubMed

    Casetti, Rita; Agrati, Chiara; Wallace, Marianne; Sacchi, Alessandra; Martini, Federico; Martino, Angelo; Rinaldi, Alessandra; Malkovsky, Miroslav

    2009-09-15

    Several subsets of alphabeta regulatory T cells (Tregs) have been described and studied intensively, but the potential regulatory role of gammadelta T cells remains largely unclear. Lymphocytes expressing gammadelta TCR are involved in both innate and adaptive immune responses, and their major adult human peripheral blood subset (Vgamma9Vdelta2) displays a broad reactivity against microbial agents and tumors. In this study we report that gammadelta T lymphocytes with regulatory functions (Vdelta2 Tregs) are induced in vitro in the presence of specific Ag stimulation and cytokines (TGF-beta1 and IL-15). These cells express FOXP3 and, similarly as alphabeta Tregs, suppress the proliferation of anti-CD3/anti-CD28 stimulated-PBMC. Phenotypic and functional analyses of Vdelta2 Tregs will very likely improve our understanding about the role of gammadelta T cells in the pathogenesis of autoimmune, infectious, and neoplastic diseases.

  7. Anticancer Cytokines: Biology and Clinical Effects of Interferon-α2, Interleukin (IL)-2, IL-15, IL-21, and IL-12.

    PubMed

    Floros, Theofanis; Tarhini, Ahmad A

    2015-08-01

    Efforts over nearly four decades have focused on ways to use cytokines to manipulate the host immune response towards cancer cell recognition and eradication. Significant advances were achieved with interleukin-2 (IL-2) and interferon-α (IFN-α), primarily in the treatment of patients with melanoma and renal cell carcinoma. However, the utility of other cytokines showing promise in the preclinical setting has not been established largely because of toxicity, the complex functionality of each cytokine and the difficulty mimicking in preclinical models the human environment. Here, we review the basic biology and the clinical experiences with IFN-α, IL-2, IL-15, IL-21, and IL-12. We will also review ongoing clinical trials and discuss future directions including potential use of cytokines in combination with other effective immunotherapy approaches that have come of age in recent years. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker

    PubMed Central

    Schmohl, Joerg U.; Felices, Martin; Todhunter, Deborah; Taras, Elizabeth; Miller, Jeffrey S.; Vallera, Daniel A.

    2016-01-01

    Background The design of a highly effective anti-cancer immune-engager would include targeting of highly drug refractory cancer stem cells (CSC). The design would promote effective antibody-dependent cell-mediated cytotoxicity (ADCC) and simultaneously promote costimulation to expand and self-sustain the effector NK cell population. Based on our bispecific NK cell engager platform we constructed a tetraspecific killer engager (TetraKE) comprising single-chain variable fragments (scFvs) binding FcγRIII (CD16) on NK cells, EpCAM on carcinoma cells and CD133 on cancer stem cells in order to promote ADCC. Furthermore, an Interleukin (IL)-15-crosslinker enhanced NK cell related proliferation resulting in a highly active drug termed 1615EpCAM133. Results Proliferation assays showed TetraKE promoted proliferation and enhanced NK cell survival. Drug-target binding, NK cell related degranulation, and IFN-γ production was specific for both tumor related antigens in EpCAM and CD133 bearing cancer cell lines. The TetraKE showed higher killing activity and superior dose dependent degranulation. Cytokine profiling showed a moderately enhanced IFN-γ production, enhanced GM-CSF production, but no evidence of induction of excessive cytokine release. Methods Assembly and synthesis of hybrid genes encoding the TetraKE were performed using DNA shuffling and ligation. The TetraKE was tested for efficacy, specificity, proliferation, survival, and cytokine production using carcinoma cell lines and functional assays measuring NK cell activity. Conclusion 1615EpCAM133 combines improved induction of ADCC with enhanced proliferation, limited cytokine response, and prolonged survival and proliferation of NK cells. By linking scFv-related targeting of carcinoma and CSCs with a sustaining IL-15 signal, our new construct shows great promise to target cancer and CSCs. PMID:27650544

  9. Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC

    PubMed Central

    Basher, Fahmin; Jeng, Emily K.; Wong, Hing; Wu, Jennifer

    2016-01-01

    Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists. PMID:26625316

  10. The sterile inflammatory response.

    PubMed

    Rock, Kenneth L; Latz, Eicke; Ontiveros, Fernando; Kono, Hajime

    2010-01-01

    The acute inflammatory response is a double-edged sword. On the one hand, it plays a key role in initial host defense, particularly against many infections. On the other hand, its aim is imprecise, and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. Although there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation-specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses.

  11. Karlson ozone sterilizer. Final report

    SciTech Connect

    Karlson, E.

    1984-05-07

    The authors have a functional sterilization system employing ozone as a sterilization agent. This final report covers the work that led to the first medical sterilizer using ozone as the sterilizing agent. The specifications and the final design were set by hospital operating room personnel and public safety standards. Work on kill tests using bacteria, viruses and fungi determined the necessary time and concentration of ozone necessary for sterilization. These data were used in the Karlson Ozone Sterilizer to determine the length of the steps of the operating cycle and the concentration of ozone to be used. 27 references.

  12. Sterilization by dry heat

    PubMed Central

    Darmady, E. M.; Hughes, K. E. A.; Jones, J. D.; Prince, D.; Tuke, Winifred

    1961-01-01

    The advantages and disadvantages of three forms of dry heat sterilization are discussed. In addition a fourth method, consisting of heating by infrared rays in vacuo, is described. This method is particularly suitable for instruments used in the operating theatre, since it can replace an autoclave where a supply of steam is not available. Recommended times and temperatures for dry heat sterilization are detailed, and are related to the thermal death point of Cl. tetani. The dangers of recontamination during the cooling process are discussed. PMID:13719782

  13. Expression of Engineered Nuclear Male Sterility in Brassica napus (Genetics, Morphology, Cytology, and Sensitivity to Temperature).

    PubMed Central

    Denis, M.; Delourme, R.; Gourret, J. P.; Mariani, C.; Renard, M.

    1993-01-01

    A dominant genetic male sterility trait obtained through transformation in rapeseed (Brassica napus) was studied in the progenies of 11 transformed plants. The gene conferring the male sterility consists of a ribonuclease gene under the control of a tapetum-specific promoter. Two ribonuclease genes, RNase T1 and barnase, were used. The chimaeric ribonuclease gene was linked to the bialophos-resistance gene, which confers resistance to the herbicide phosphinotricine (PPT). The resistance to the herbicide was used as a dominant marker for the male sterility trait. The study presented here concerns three aspects of this engineered male sterility: genetics correlated with the segregation of the T-DNA in the progenies; expression of the male sterility in relation to the morphology and cytology of the androecium; and stability of the engineered male sterility under different culture conditions. Correct segregation, 50% male-sterile, PPT-resistant plants, and 50% male-fertile, susceptible plants were observed in the progeny of seven transformants. The most prominent morphological change in the male-sterile flowers was a noticeable reduction in the length of the stamen filament. The first disturbances of microsporogenesis were observed from the free microspore stage and were followed by a simultaneous degeneration of microspore and tapetal cell content. At anthesis, the sterile anthers contained only empty exines. In some cases, reversion to fertility of male-sterile plants has been observed. Both ribonuclease genes are susceptible to instability. Instability of the RNase T1-male sterility trait increased at temperatures higher than 25[deg] C. Our results do not allow us to confirm this observation for the barnase male-sterile plants. However, the male-sterile plants of the progeny of two independent RNase T1 transformants were stably male sterile under all conditions studied. PMID:12231785

  14. Heat sterilization of wood

    Treesearch

    Xiping Wang

    2010-01-01

    Two important questions should be considered in heat sterilizing solid wood materials: First, what temperature–time regime is required to kill a particular pest? Second, how much time is required to heat the center of any wood configuration to the kill temperature? The entomology research on the first question has facilitated the development of international standards...

  15. Sterilization of Native Americans

    ERIC Educational Resources Information Center

    Dillingham, Brint

    1977-01-01

    The U.S. State Department's Agency for International Development (AID) is spending more than $143 million this year for population control measures in over 70 nations around the world and it is estimated that as much as $10 million was spent in one year for surgical sterilization procedures. (JC)

  16. Radiation sterilization of ketoprofen

    NASA Astrophysics Data System (ADS)

    Katušin-Ražem, Branka; Hamitouche, Katia; Maltar-Strmečki, Nadica; Kos, Karmen; Pucić, Irina; Britvić-Budicin, Smiljana; Ražem, Dušan

    2005-06-01

    Radiation sterilization of ketoprofen (KP) dry powder was investigated by selected physico-chemical methods. High-performance liquid chromatography, ultraviolet spectrophotometry, infrared spectrophotometry, differential scanning calorimetry, X-ray diffraction and electron spin resonance spectroscopy did not show any significant degradation at sterilization dose 25 kGy. To determine the nature, extent and direction of radiation-induced changes, KP was irradiated to extremely high doses, much higher than necessary to achieve sterility. The irradiated KP did not show any difference of XRD patterns up to 200 kGy; with DSC and IR some changes were detected only above 1000 and 2000 kGy, respectively; HPLC has shown about 5% destruction at 2000 kGy. Acetyl benzophenon (AcBph) was generated by irradiation with G(AcBph)=(1.6±0.1)×10 -8 mol J -1. Ames test has shown no mutagenicity of KP irradiated with 3000 kGy or of the oily mixure of radiolytic products isolated from it. Solid KP has proven to be very stable on irradiation, and irradiation has been found to be a suitable method for its sterilization.

  17. MINOS Sterile Neutrino Search

    SciTech Connect

    Koskinen, David Jason

    2009-02-01

    The Main Injector Neutrino Oscillation Search (MINOS) is a long-baseline accelerator neutrino experiment designed to measure properties of neutrino oscillation. Using a high intensity muon neutrino beam, produced by the Neutrinos at Main Injector (NuMI) complex at Fermilab, MINOS makes two measurements of neutrino interactions. The first measurement is made using the Near Detector situated at Fermilab and the second is made using the Far Detector located in the Soudan Underground laboratory in northern Minnesota. The primary goal of MINOS is to verify, and measure the properties of, neutrino oscillation between the two detectors using the v μ→ Vτ transition. A complementary measurement can be made to search for the existence of sterile neutrinos; an oft theorized, but experimentally unvalidated particle. The following thesis will show the results of a sterile neutrino search using MINOS RunI and RunII data totaling ~2.5 x 1020 protons on target. Due to the theoretical nature of sterile neutrinos, complete formalism that covers transition probabilities for the three known active states with the addition of a sterile state is also presented.

  18. Sterilization surgery - making a decision

    MedlinePlus

    ... medlineplus.gov/ency/article/002138.htm Sterilization surgery - making a decision To use the sharing features on this page, ... about all the options available to you before making the decision to have a sterilization procedure. Alternative Names Deciding ...

  19. Identification of Coupling and Repulsion Phase DNA Marker Associated With an Allele of a Gene Conferring Host Plant Resistance to Pigeonpea sterility mosaic virus (PPSMV) in Pigeonpea (Cajanus cajan L. Millsp.)

    PubMed Central

    Daspute, Abhijit; Fakrudin, B.

    2015-01-01

    Pigeonpea Sterility Mosaic Disease (PSMD) is an important foliar disease caused by Pigeonpea sterility mosaic virus (PPSMV) which is transmitted by eriophyid mites (Aceria cajani Channabasavanna). In present study, a F2 mapping population comprising 325 individuals was developed by crossing PSMD susceptible genotype (Gullyal white) and PSMD resistant genotype (BSMR 736). We identified a set of 32 out of 300 short decamer random DNA markers that showed polymorphism between Gullyal white and BSMR 736 parents. Among them, eleven DNA markers showed polymorphism including coupling and repulsion phase type of polymorphism across the parents. Bulked Segregant Analysis (BSA), revealed that the DNA marker, IABTPPN7, produced a single coupling phase marker (IABTPPN7414) and a repulsion phase marker (IABTPPN7983) co-segregating with PSMD reaction. Screening of 325 F2 population using IABTPPN7 revealed that the repulsion phase marker, IABTPPN7983, was co-segregating with the PSMD responsive SV1 at a distance of 23.9 cM for Bidar PPSMV isolate. On the other hand, the coupling phase marker IABTPPN7414 did not show any linkage with PSMD resistance. Additionally, single marker analysis both IABTPPN7983 (P<0.0001) and IABTPPN 7414 (P<0.0001) recorded a significant association with the PSMD resistance and explained a phenotypic variance of 31 and 36% respectively in F2 population. The repulsion phase marker, IABTPPN7983, could be of use in Marker-Assisted Selection (MAS) in the PPSMV resistance breeding programmes of pigeonpea. PMID:25774108

  20. 21 CFR 880.6850 - Sterilization wrap.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sterilization wrap. 880.6850 Section 880.6850 Food... § 880.6850 Sterilization wrap. (a) Identification. A sterilization wrap (pack, sterilization wrapper... sterilized by a health care provider. It is intended to allow sterilization of the enclosed medical device...

  1. 21 CFR 880.6850 - Sterilization wrap.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Sterilization wrap. 880.6850 Section 880.6850 Food... § 880.6850 Sterilization wrap. (a) Identification. A sterilization wrap (pack, sterilization wrapper... sterilized by a health care provider. It is intended to allow sterilization of the enclosed medical device...

  2. Nanoparticle-mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL-15-dependent DC crosstalk.

    PubMed

    Sehgal, Kartik; Ragheb, Ragy; Fahmy, Tarek M; Dhodapkar, Madhav V; Dhodapkar, Kavita M

    2014-09-01

    Most vaccines depend on coadministration of Ags and adjuvants that activate APCs. Nanoparticles (NPs) have emerged as an attractive vehicle for synchronized delivery of Ags and adjuvants to APCs and can be targeted to specific cell types, such as dendritic cells (DCs), which are potent APCs. Which subset of human DCs should be targeted for optimal activation of T cell immunity, however, remains unknown. In this article, we describe a poly-lactic-coglycolic acid-based NP platform, wherein avidin-decorated NPs can be targeted to multiple human DC subsets via biotinylated Abs. Both BDCA3(+) and monocyte-derived DC-SIGN(+) NP-loaded DCs were equally effective at generating Ag-specific human T cells in culture, including against complex peptide mixtures from viral and tumor Ags across multiple MHC molecules. Ab-mediated targeting of NPs to distinct DC subsets led to enhanced T cell immunity. However, combination targeting to both DC-SIGN and BDCA3(+) DCs led to significantly greater activation of T cells compared with targeting either DC subset alone. Enhanced T cell activation following combination targeting depended on DC-mediated cytokine release and was IL-15 dependent. These data demonstrate that simultaneous targeting of multiple DC subsets may improve NP vaccines by engaging DC crosstalk and provides a novel approach to improving vaccines against pathogens and tumors.

  3. Phenotypic and Functional Dysregulated Blood NK Cells in Colorectal Cancer Patients Can Be Activated by Cetuximab Plus IL-2 or IL-15

    PubMed Central

    Rocca, Yamila Sol; Roberti, María Paula; Juliá, Estefanía Paula; Pampena, María Betina; Bruno, Luisina; Rivero, Sergio; Huertas, Eduardo; Sánchez Loria, Fernando; Pairola, Alejandro; Caignard, Anne; Mordoh, José; Levy, Estrella Mariel

    2016-01-01

    The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression. We observed profound deregulation in receptor expression even in early stages of disease compared with HD. CRC-NK cells displayed underexpression of CD16, NKG2D, DNAM-1, CD161, NKp46, and NKp30 activating receptors, while inhibitory receptors CD85j and NKG2A were overexpressed. This inhibited phenotype affected cytotoxic functionality against CRC cells and interferon-γ production. We also determined that NKp30 and NKp46 are the key receptors involved in detriment of CRC-NK cells’ antitumor activity. Moreover, NKp46 expression correlated with relapse-free survival of CRC patients with a maximum follow-up of 71 months. CRC-NK cells also exhibited altered antibody-dependent cellular cytotoxicity function responding poorly to cetuximab. IL-2 and IL-15 in combination with cetuximab stimulated NK cell, improving cytotoxicity. These results show potential strategies to enhance CRC-NK cell activity. PMID:27777574

  4. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15

    PubMed Central

    Xu, Yang; Zhang, Ming; Ramos, Carlos A.; Durett, April; Liu, Enli; Dakhova, Olga; Liu, Hao; Creighton, Chad J.; Gee, Adrian P.; Heslop, Helen E.; Rooney, Cliona M.; Savoldo, Barbara

    2014-01-01

    Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies. Although in vivo persistence of CAR-T cells correlates with clinical responses, it remains unknown whether specific cell subsets within the CAR–T-cell product correlate with their subsequent in vivo expansion and persistence. We analyzed 14 patients with B-cell malignancies infused with autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found that their in vivo expansion only correlated with the frequency within the infused product of a CD8+CD45RA+CCR7+ subset, whose phenotype is closest to “T-memory stem cells.” Preclinical models showed that increasing the frequency of CD8+CD45RA+CCR7+ CAR-T cells in the infused line by culturing the cells with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated by increased resistance to cell death, following repetitive encounters with the antigen, while preserving their migration to secondary lymphoid organs. This trial was registered at www.clinicaltrials.gov as #NCT00586391 and #NCT00709033. PMID:24782509

  5. Peripheral human CD4(+)CD8(+) T lymphocytes exhibit a memory phenotype and enhanced responses to IL-2, IL-7 and IL-15.

    PubMed

    Clénet, Marie-Laure; Gagnon, François; Moratalla, Ana Carmena; Viel, Emilie C; Arbour, Nathalie

    2017-09-14

    CD4(+)CD8(+) T lymphocytes account for 1-2% of circulating human T lymphocytes, but their frequency is augmented in several diseases. The phenotypic and functional properties of these T lymphocytes are still ill-defined. We performed an ex vivo characterization of CD4(+)CD8(+) T lymphocytes from the blood of healthy individuals. We observed that CD4(+)CD8(+) T lymphocytes exhibit several characteristics associated with memory T lymphocytes including the expression of chemokine receptors (e.g. CCR7, CXCR3, CCR6) and activation markers (e.g. CD57, CD95). Moreover, we showed that a greater proportion of CD4(+)CD8(+) T lymphocytes have an enhanced capacity to produce cytokines (IFNγ, TNFα, IL-2, IL-4, IL-17A) and lytic enzymes (perforin, granzyme B) compared to CD4(+) and/or CD8(+) T lymphocytes. Finally, we assessed the impact of three key cytokines in T cell biology on these cells. We observed that IL-2, IL-7 and IL-15 triggered STAT5 phosphorylation in a greater proportion of CD4(+)CD8(+) T lymphocytes compared to CD4 and CD8 counterparts. We demonstrate that CD4(+)CD8(+) T lymphocytes from healthy donors exhibit a phenotypic profile associated with memory T lymphocytes, an increased capacity to produce cytokines and lytic enzymes, and a higher proportion of cells responding to key cytokines implicated in T cell survival, homeostasis and activation.

  6. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15.

    PubMed

    Xu, Yang; Zhang, Ming; Ramos, Carlos A; Durett, April; Liu, Enli; Dakhova, Olga; Liu, Hao; Creighton, Chad J; Gee, Adrian P; Heslop, Helen E; Rooney, Cliona M; Savoldo, Barbara; Dotti, Gianpietro

    2014-06-12

    Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies. Although in vivo persistence of CAR-T cells correlates with clinical responses, it remains unknown whether specific cell subsets within the CAR-T-cell product correlate with their subsequent in vivo expansion and persistence. We analyzed 14 patients with B-cell malignancies infused with autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found that their in vivo expansion only correlated with the frequency within the infused product of a CD8(+)CD45RA(+)CCR7(+) subset, whose phenotype is closest to "T-memory stem cells." Preclinical models showed that increasing the frequency of CD8(+)CD45RA(+)CCR7(+) CAR-T cells in the infused line by culturing the cells with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated by increased resistance to cell death, following repetitive encounters with the antigen, while preserving their migration to secondary lymphoid organs. This trial was registered at www.clinicaltrials.gov as #NCT00586391 and #NCT00709033.

  7. Natural Killer Cell Subsets and IL-2, IL-15, and IL-18 Genes Expressions in Chronic Kidney Allograft Dysfunction and Graft Function in Kidney Allograft Recipients

    PubMed Central

    Assadiasl, S.; Sepanjnia, A.; Aghili, B.; Nafar, M.; Ahmadpoor, P.; Pourrezagholi, F.; Parvin, M.; Shahlaee, A.; Nicknam, M. H.; Amirzargar, A.

    2016-01-01

    Background: While acute rejection and early graft loss rates have decreased substantially over the past four decades, progressive chronic allograft dysfunction (CAD) still remains a common cause of late graft loss in kidney transplant recipients. Objective: This study was conducted to investigate the percentage of natural killer (NK) cell subsets and IL-2, 15 and 18 genes expression in two groups of CAD and well-function graft (WFG) recipients. Methods: 30 renal allograft recipients with biopsy-proven interstitial fibrosis/tubular atrophy (IF/TA) and impaired renal function, and 30 sex- and age-matched WFG patients were enrolled in this study. The percentage of NK cell subsets including NK CD56bright and NK CD56dim cells were determined by flowcytometry; IL-2, IL-15, and IL-18 genes expressions were assessed by real-time PCR. Results: Compared to WFG patients, there was a significant (p<0.05) increase in the percentage of NK CD56bright cells in CAD patients. However, the difference in percentage of NK CD56dim cells or CD56dim/CD56bright ratio between the studied groups was not significant. In addition, IL-2, 15 and 18 genes expressions were almost similar in CAD and WFG patients. Conclusion: We found higher percentages of NK CD56bright subset in kidney transplant recipients with CAD without considerable changes in related cytokines’ gene expression, suggesting a possible defect of NK cells maturation in these patients. PMID:28078060

  8. Sterilization of Medical Instruments

    DTIC Science & Technology

    2007-05-06

    possible use with medical instruments and skin catheters. To address this challenge, MicroStructure Technologies (MicroST) is developing an...Project: DARPA - Sterilization of Medical Instruments Contract: # FA9550-06-C-0054 Principal Investigator: Joseph Birmingham Report: FINAL Report 1...as medical instruments and skin catheters. To address this challenge, MicroStructure Technologies (MicroST) is proposing a compact, low maintenance

  9. Sterilization by oxygen plasma

    NASA Astrophysics Data System (ADS)

    Moreira, Adir José; Mansano, Ronaldo Domingues; Andreoli Pinto, Terezinha de Jesus; Ruas, Ronaldo; Zambon, Luis da Silva; da Silva, Mônica Valero; Verdonck, Patrick Bernard

    2004-07-01

    The use of polymeric medical devices has stimulated the development of new sterilization methods. The traditional techniques rely on ethylene oxide, but there are many questions concerning the carcinogenic properties of the ethylene oxide residues adsorbed on the materials after processing. Another common technique is the gamma irradiation process, but it is costly, its safe operation requires an isolated site and it also affects the bulk properties of the polymers. The use of a gas plasma is an elegant alternative sterilization technique. The plasma promotes an efficient inactivation of the micro-organisms, minimises the damage to the materials and presents very little danger for personnel and the environment. Pure oxygen reactive ion etching type of plasmas were applied to inactivate a biologic indicator, the Bacillus stearothermophilus, to confirm the efficiency of this process. The sterilization processes took a short time, in a few minutes the mortality was complete. In situ analysis of the micro-organisms' inactivating time was possible using emission spectrophotometry. The increase in the intensity of the 777.5 nm oxygen line shows the end of the oxidation of the biologic materials. The results were also observed and corroborated by scanning electron microscopy.

  10. Construction of a high-resolution linkage map of Rfd1, a restorer-of-fertility locus for cytoplasmic male sterility conferred by DCGMS cytoplasm in radish (Raphanus sativus L.) using synteny between radish and Arabidopsis genomes.

    PubMed

    Cho, Youngcho; Lee, Young-Pyo; Park, Beom-Seok; Han, Tae-Ho; Kim, Sunggil

    2012-08-01

    Cytoplasmic male sterility caused by Dongbu cytoplasmic and genic male-sterility (DCGMS) cytoplasm and its nuclear restorer-of-fertility locus (Rfd1) with a linked molecular marker (A137) have been reported in radish (Raphanus sativus L.). To construct a linkage map of the Rfd1 locus, linked amplified fragment length polymorphism (AFLP) markers were screened using bulked segregant analysis. A 220-bp linked AFLP fragment sequence from radish showed homology with an Arabidopsis coding sequence. Using this Arabidopsis gene sequence, a simple PCR marker (A220) was developed. The A137 and A220 markers flanked the Rfd1 locus. Two homologous Arabidopsis genes with both marker sequences were positioned on Arabidopsis chromosome-3 with an interval of 2.4 Mb. To integrate the Rfd1 locus into a previously reported expressed sequence tag (EST)-simple sequence repeat (SSR) linkage map, the radish EST sequences located in three syntenic blocks within the 2.4-Mb interval were used to develop single nucleotide polymorphism (SNP) markers for tagging each block. The SNP marker in linkage group-2 co-segregated with male fertility in an F(2) population. Using radish ESTs positioned in linkage group-2, five intron length polymorphism (ILP) markers and one cleaved amplified polymorphic sequence (CAPS) marker were developed and used to construct a linkage map of the Rfd1 locus. Two closely linked markers delimited the Rfd1 locus within a 985-kb interval of Arabidopsis chromosome-3. Synteny between the radish and Arabidopsis genomes in the 985-kb interval were used to develop three ILP and three CAPS markers. Two ILP markers further delimited the Rfd1 locus to a 220-kb interval of Arabidopsis chromosome-3.

  11. Hysteroscopic Tubal Sterilization

    PubMed Central

    2013-01-01

    Background Hysteroscopic sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. In contrast to the laparoscopic technique, a hysteroscope is used to pass permanent microinserts through the cervix and place them in the fallopian tubes. This procedure does not require local or general anesthesia and can be performed in an office setting. Objectives The objective of this analysis was to determine, based on published literature, the cost-effectiveness of hysteroscopic tubal sterilization (HS) compared with laparoscopic tubal ligation (LS) for permanent female sterilization. Data Sources A systematic literature search was conducted for studies published between January 1, 2008, and December 11, 2012. Review Methods Potentially relevant studies were identified based on the title and abstract. Cost-utility analyses (studies that report outcomes in terms of costs and quality-adjusted life-years) were prioritized for inclusion. When not available, cost-effectiveness, cost-benefit, and cost-consequence analyses were considered. Costing studies were considered in the absence of all other analyses. Results A total of 33 abstracts were identified. Three cost analyses were included. A retrospective chart review from Canada found that HS was $111 less costly than LS; a prospective activity-based cost management study from Italy reported that it was €337 less costly than LS; and the results of an American decision model showed that HS was $1,178 less costly than LS. Limitations All studies had limited applicability to the Ontario health care system due to differences in setting, resource use, and costs. Conclusions Three cost analyses found that, although the HS procedure was more expensive due to the cost of the microinserts, HS was less costly than LS overall due to the shorter recovery time required. Plain Language Summary Hysteroscopic sterilization is a minimally invasive alternative to conventional tubal

  12. [Studies on the method of sterilization with ethylene oxide gas. 1. Sterilization procedure and sterilizing effect].

    PubMed

    Arimoto, H; Ukisu, S; Yamada, Y; Sano, K; Kanri, T

    1989-12-01

    Undertaken to ensure perfection of sterilization with ethylene oxide gas (EO gas) in routine clinical laboratory practice, an investigation was made of the relationship between sterilization procedure and sterilizing effect using the film bag delivery system and chamber system. Using a biological indicator as a monitor of sterilizing effect, the efficiency of sterilization was studied under various likely conditions and compared. The results led to the following conclusions: 1. Sterilization with EO gas by the film bag delivery system, because of this procedure being unable to be performed at a constant temperature, was shown to prove inadequate due to insufficient exposure to gas especially in winter season (when room temperature fell below 10 degrees C). 2. With the EO gas sterilization method using the film bag delivery system, which is believed to be effective within the ordinary range of humidity of the atmosphere, sterilizing effect was recognized to be affected by excess wetting of an object of sterilization that was caused by inadvertent manipulation or due to a predisposing attribute of the object, such as shape or outline. 3. All materials are sterilized upon being packaged. It is necessary therefore to make best choice of package material with respect of texture and size. Reuse influence to sterilizing effect. 4. The method of sterilization with EO gas using the chamber system has the advantage in that operating conditions are all automatically controlled. For this reason, there was not a single instance of failure to sterilize due to inappropriateness of temperature and humidity. From these results it is concluded that sterilising effect was affected by sterilization procedure and condition.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. NK cells are primed by ANRS MVA(HIV)-infected DCs, via a mechanism involving NKG2D and membrane-bound IL-15, to control HIV-1 infection in CD4+ T cells.

    PubMed

    Moreno-Nieves, Uriel Y; Didier, Céline; Lévy, Yves; Barré-Sinoussi, Françoise; Scott-Algara, Daniel

    2014-08-01

    Natural killer (NK) cells are the major antiviral effector cell population of the innate immune system. It has been demonstrated that NK-cell activity can be modulated by the interaction with dendritic cells (DCs). The HIV-1 vaccine candidate Modified Vaccinia Ankara encoding an HIV polypeptide (MVA(HIV)), developed by the French National Agency for Research on AIDS (ANRS), has the ability to prime NK cells to control HIV-1 infection in DCs. However, whether or not MVA(HIV)-primed NK cells are able to better control HIV-1 infection in CD4(+) T cells, and the mechanism underlying the specific priming, remain undetermined. In this study, we show that MVA(HIV)-primed NK cells display a greater capacity to control HIV-1 infection in autologous CD4(+) T cells. We also highlight the importance of NKG2D engagement on NK cells and DC-produced IL-15 to achieve the anti-HIV-1 specific priming, as blockade of either NKG2D or IL-15 during MVA(HIV)-priming lead to a subsequent decreased control of HIV-1 infection in autologous CD4(+) T cells. Furthermore, we show that the decreased control of HIV-1 infection in CD4(+) T cells might be due, at least in part, to the decreased expression of membrane-bound IL-15 (mbIL-15) on DCs when NKG2D is blocked during MVA(HIV)-priming of NK cells.

  14. Memory-Like Antigen-Specific Human NK Cells from TB Pleural Fluids Produced IL-22 in Response to IL-15 or Mycobacterium tuberculosis Antigens.

    PubMed

    Fu, Xiaoying; Yu, Sifei; Yang, Binyan; Lao, Suihua; Li, Baiqing; Wu, Changyou

    2016-01-01

    Our previous result indicated that memory-like human natural killer (NK) cells from TB pleural fluid cells (PFCs) produced large amounts of IFN-γ in response to Bacille Calmette Guerin (BCG). Furthermore, recent studies have shown that human lymphoid tissues harbored a unique NK cell subset that specialized in production of interleukin (IL)-22, a proinflammatory cytokine that mediates host defense against pathogens. Yet little information was available with regard to the properties of IL-22 production by memory-like human NK cells. In the present study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL-22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the subset of specific IL-22-producing NK cells were distinct from IFN-γ-producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured with autologous monocytes and stimulated with BCG for the production of IL-22. The result demonstrated that CD45RO+ but not CD45RO- NK cells produced significantly higher level of IL-22. Anti-IL-12Rβ1 mAbs (2B10) partially inhibit the expression of IL-22 by NK cells under the culture with BCG. Consistently, BCG specific IL-22-producing NK cells from PFCs expressed CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that memory-like antigen-specific CD45RO+ NK cells might participate in the recall immune response for M. tb infection via producing IL-22, which display a critical role to fight against M. tb.

  15. An international overview of sterilization.

    PubMed

    Dourlen-Rollier, A M

    1977-05-01

    Sterilization, both male and female, for family planning purposes developed very rapidly, beginning in Puerto Rico and Japan between 1940 and 1950 and continuing in India and Pakistan on a large scale after the mid-1950s. The legal status of voluntary sterilization around the world is confused, but recent developments show a trend toward liberalization of the laws. Certain countries still consider sterilization punishable under the criminal law, but there is a gap between the law and the practice. Certain countries have made the issue of consent relevant under the law. Certain other governments are studying the question of sterilization officially. Countries with heavy population pressures are employing incentives to encourage sterilization and others, specifically European countries, have legally authorized sterilization. The procedure is becoming increasingly accepted.

  16. Sterilization in the United States

    PubMed Central

    Bartz, Deborah; Greenberg, James A

    2008-01-01

    Unintended pregnancies are expensive for patients and for society in terms of medical costs, the cost of caring for more children, and the cost to personal and professional goals. Sterilization is the most common contraceptive method utilized by couples in the United States. Given technological advances over the past few decades, male and female surgical sterilization has become a safe, convenient, easy, and highly effective birth control method for the long term. This article reviews current male and female sterilization options. PMID:18701927

  17. Sterile neutrinos: fact or fiction?

    NASA Astrophysics Data System (ADS)

    Huber, Patrick

    2017-01-01

    In this talk I will critically review some of the anomalies which in combination could point to the existence of a eV-scale sterile neutrino. Each of these anomalies is well below the 5 sigma level individually and may have explanations besides sterile neutrinos. At the same time each anomaly requires a separate explanation if it is not caused by a sterile neutrino. To further complicate the gpicture, some data sets are in mutual disagreement.

  18. Post-tubal sterilization syndrome.

    PubMed

    Lethbridge, D J

    1992-01-01

    This article presents a review of the literature on post-tubal sterilization syndrome. Although studies have shortcomings they suggest the majority of women undergoing tubal sterilization do not experience changes in menstrual patterns after the procedure, but a minority do. Suggestions are made for further research, conducted from a nursing perspective. Implications for practice are suggested, given the tentative information on post-tubal sterilization syndrome.

  19. New disinfection and sterilization methods.

    PubMed Central

    Rutala, W. A.; Weber, D. J.

    2001-01-01

    New disinfection methods include a persistent antimicrobial coating that can be applied to inanimate and animate objects (Surfacine), a high-level disinfectant with reduced exposure time (ortho-phthalaldehyde), and an antimicrobial agent that can be applied to animate and inanimate objects (superoxidized water). New sterilization methods include a chemical sterilization process for endoscopes that integrates cleaning (Endoclens), a rapid (4-hour) readout biological indicator for ethylene oxide sterilization (Attest), and a hydrogen peroxide plasma sterilizer that has a shorter cycle time and improved efficacy (Sterrad 50). PMID:11294738

  20. CD4⁺CD28null T lymphocytes resemble CD8⁺CD28null T lymphocytes in their responses to IL-15 and IL-21 in HIV-infected patients.

    PubMed

    Echeverría, Ainara; Moro-García, Marco A; Asensi, Víctor; Cartón, José A; López-Larrea, Carlos; Alonso-Arias, Rebeca

    2015-09-01

    HIV-infected individuals suffer from accelerated immunologic aging. One of the most prominent changes during T lymphocyte aging is the accumulation of CD28(null) T lymphocytes, mainly CD8(+) but also CD4(+) T lymphocytes. Enhancing the functional properties of these cells may be important because they provide antigen-specific defense against chronic infections. The objective of this study was to compare the responses of CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes from HIV-infected patients to the immunomodulatory effects of cytokines IL-15 and IL-21. We quantified the frequencies of CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes in peripheral blood from 110 consecutive, HIV-infected patients and 25 healthy controls. Patients showed increased frequencies of CD4(+)CD28(null) and CD8(+)CD28(null). Both subsets were positively correlated to each other and showed an inverse correlation with the absolute counts of CD4(+) T lymphocytes. Higher frequencies of HIV-specific and CMV-specific cells were found in CD28(null) than in CD28(+) T lymphocytes. Activation of STAT5 by IL-15 and STAT3 by IL-21 was higher in CD28(null) compared with CD28(+) T lymphocytes. Proliferation, expression of CD69, and IFN-γ production in CD28(null) T lymphocytes were increased after treatment with IL-15, and IL-21 potentiated most of those effects. Nevertheless, IL-21 alone reduced IFN-γ production in response to anti-CD3 stimulation but increased CD28 expression, even counteracting the inhibitory effect of IL-15. Intracytoplasmic stores of granzyme B and perforin were increased by IL-15, whereas IL-21 and simultaneous treatment with the 2 cytokines also significantly enhanced degranulation in CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes. IL-15 and IL-21 could have a role in enhancing the effector response of CD28(null) T lymphocytes against their specific chronic antigens in HIV-infected patients.

  1. Sterilization of Extracted Human Teeth.

    ERIC Educational Resources Information Center

    Pantera, Eugene A., Jr.; Schuster, George S.

    1990-01-01

    At present, there is no specific recommendation for sterilization of extracted human teeth used in dental technique courses. The purpose of this study was to determine whether autoclaving would be effective in the sterilization of extracted teeth without compromising the characteristics that make their use in clinical simulations desirable. (MLW)

  2. Sterilization of Extracted Human Teeth.

    ERIC Educational Resources Information Center

    Pantera, Eugene A., Jr.; Schuster, George S.

    1990-01-01

    At present, there is no specific recommendation for sterilization of extracted human teeth used in dental technique courses. The purpose of this study was to determine whether autoclaving would be effective in the sterilization of extracted teeth without compromising the characteristics that make their use in clinical simulations desirable. (MLW)

  3. Ethylene Oxide Gaseous Sterilization

    PubMed Central

    Ernst, Robert R.; Shull, James J.

    1962-01-01

    The duration of the equilibration period between admission of water vapor and subsequent introduction of gaseous ethylene oxide to an evacuated sterilizer chamber was studied with respect to its effect on the inactivation of spores of Bacillus subtilis var. niger under simulated practical conditions. Introduction of a water-adsorbing cotton barrier between the spores and an incoming gas mixture of water vapor and ethylene oxide caused a marked increase in the observed thermochemical death time of the spore populations. This effect was negated by admission of water vapor one or more minutes prior to introduction of ethylene oxide gas. Increases in temperature and relative humidity of the system promoted passage of water vapor through the cotton barriers and diminished their effect. PMID:13890660

  4. Sterile Inflammation in Drosophila

    PubMed Central

    Shaukat, Zeeshan; Liu, Dawei; Gregory, Stephen

    2015-01-01

    The study of immune responses in Drosophila has already yielded significant results with impacts on our understanding of vertebrate immunity, such as the characterization of the Toll receptor. Several recent papers have focused on the humoral response to damage signals rather than pathogens, particularly damage signals from tumour-like tissues generated by loss of cell polarity or chromosomal instability. Both the triggers that generate this sterile inflammation and the systemic and local effects of it are only just beginning to be characterized in Drosophila. Here we review the molecular mechanisms that are known that give rise to the recruitment of Drosophila phagocytes, called hemocytes, as well as the signals, such as TNFα, that stimulated hemocytes emit at sites of perceived damage. The signalling consequences of inflammation, such as the activation of JNK, and the potential for modifying this response are also discussed. PMID:25948885

  5. Steam sterilization of laparoscopic instruments.

    PubMed

    Voyles, C R; Sanders, D L; Simons, J E; McVey, E A; Wilson, W B

    1995-04-01

    Because of the intricate internal parts of laparoscopic instruments, questions have been raised about the efficacy of cleaning and sterilization techniques. To assess these risks, hamburger meat was inoculated with high concentrations of vegetative pathogens and packed into laparoscopic cannulas. All openings of the cannulas were sealed during steam sterilization cycles ranging from 3 to 10 min in different experiments; cultures were obtained after cooling. Experiments were then performed using heat-resistant spore forms. Our studies showed that both the standard 10-min cycle and the 3-min "flash" were uniformly successful in killing all pathogenic microorganisms. A 7-min steam sterilization was necessary to kill spores within sealed cannulas. We conclude that a standard 10-min cycle within the steam autoclave provides complete sterilization of laparoscopic instruments; the 3-min "flash" sterilization is appropriate and safe for instruments that have been inadvertently contaminated or dropped during a surgical procedure.

  6. Electrolytic silver ion cell sterilizes water supply

    NASA Technical Reports Server (NTRS)

    Albright, C. F.; Gillerman, J. B.

    1968-01-01

    Electrolytic water sterilizer controls microbial contamination in manned spacecraft. Individual sterilizer cells are self-contained and require no external power or control. The sterilizer generates silver ions which do not impart an unpleasant taste to water.

  7. Safety and Immunogenicity of an HIV-1 Gag DNA Vaccine with or without IL-12 and/or IL-15 Plasmid Cytokine Adjuvant in Healthy, HIV-1 Uninfected Adults

    PubMed Central

    Kalams, Spyros A.; Parker, Scott; Jin, Xia; Elizaga, Marnie; Metch, Barbara; Wang, Maggie; Hural, John; Lubeck, Michael; Eldridge, John; Cardinali, Massimo; Blattner, William A.; Sobieszczyk, Magda; Suriyanon, Vinai; Kalichman, Artur; Weiner, David B.; Baden, Lindsey R.

    2012-01-01

    Background DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques. Methodology/Principal Findings We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response. Conclusions/Significance This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity. Trial Registration Clinicaltrials.gov NCT00115960 NCT00111605 PMID:22242162

  8. Pain Associated With Hysteroscopic Sterilization

    PubMed Central

    Levy, Jenna; Childers, Meredith E.

    2007-01-01

    Background and Objectives: The safety and efficacy of female hysteroscopic sterilization using the Essure system has been well documented. Given the marked differences in the execution of hysteroscopic and laparoscopic sterilization, the objective of this study was to assess the experience of pain postprocedure between the 2. Secondary end-points included postoperative pain medication, time to return to normal activities, postprocedure bleeding, and patient satisfaction. Methods: Twenty cases each of laparoscopic sterilization (LS) and hysteroscopic sterilization (HS) were performed. Patients were surveyed regarding their experience of pain immediately postoperatively, 1 week, and 4 weeks post-procedure. Results: The average pain score immediately postprocedure was significantly lower among HS patients than among LS patients (t=−8.17, P<.0001). One-week post-procedure, none of the patients in the HS group reported any pain, while the average pain score among the LS patients was 2.65 (t =−9.67, P<.0001). Four weeks post-procedure, women in the HS group continued to report no pain, 35% of the LS group continued to report some pain (t=−3.04, P=.004). Conclusions: Hysteroscopic sterilization offers a minimally invasive, less painful, equally efficacious modality for sterilization than laparoscopic sterilization and should be available to all women seeking permanent birth control. PMID:17651558

  9. Portable Decontamination and Sterilization System

    DTIC Science & Technology

    2004-11-17

    No external power required • Gas-phase sterilant generated by chemical reaction • Sterilant is chlorine dioxide, ClO2 • Rapid, proven effective in...earlier studies • Solutions of ClO2 in water are effective against VX and HD on surfaces; no data for gaseous ClO2 with CW agents • ClO2 is effective...ingredients • Sterilizer bag design (single use) • Indicators • Vent with ClO2 scavenger • Overwrap TDA R e s e a r c h Generation of ClO2 • Widely

  10. Sterile Keratitis following Collagen Crosslinking.

    PubMed

    Javadi, Mohammad-Ali; Feizi, Sepehr

    2014-01-01

    To report a keratoconic eye that developed severe sterile keratitis and corneal scar after collagen crosslinking necessitating corneal transplantation. A 26-year-old man with progressive keratoconus underwent collagen crosslinking and presented with severe keratitis 72 hours after the procedure. The initial impression was infectious corneal ulcer and a fortified antibiotic regimen was administered. However, the clinical course and confocal microscopy results prompted a diagnosis of sterile keratitis. The eye developed severe corneal scars leading to reduced visual acuity and necessitating corneal transplantation. Sterile keratitis may develop after collagen crosslinking resulting in profound visual loss leading to corneal transplantation.

  11. Food irradiation and sterilization

    NASA Astrophysics Data System (ADS)

    Josephson, Edward S.

    Radiation sterilization of food (radappertization) requires exposing food in sealed containers to ionizing radiation at absorbed doses high enough (25-70 kGy) to kill all organisms of food spoilage and public health significance. Radappertization is analogous to thermal canning is achieving shelf stability (long term storage without refrigeration). Except for dry products in which autolysis is negligible, the radappertization process also requires that the food be heated to an internal temperature of 70-80°C (bacon to 53°C) to inactivate autolytic enzymes which catalyze spoilage during storage without refrigeration. To minimize the occurence of irradiation induced off-flavors and odors, undesirable color changes, and textural and nutritional losses from exposure to the high doses required for radappertization, the foods are vacuum sealed and irradiated frozen (-40°C to -20°C). Radappertozed foods have the characteristic of fresh foods prepared for eating. Radappertization can substitute in whole or in part for some chemical food additives such as ethylene oxide and nitrites which are either toxic, carcinogenic, mutagenic, or teratogenic. After 27 years of testing for "wholesomeness" (safety for consumption) of radappertized foods, no confirmed evidence has been obtained of any adverse effecys of radappertization on the "wholesomeness" characteristics of these foods.

  12. Stress-activated Dendritic Cells (DC) Induce Dual Interleukin (IL)-15- and IL1β-mediated Pathways, Which May Elicit CD4+ Memory T Cells and Interferon (IFN)-stimulated Genes.

    PubMed

    Wang, Yufei; Lavender, Paul; Watson, Julie; Arno, Matthew; Lehner, Thomas

    2015-06-19

    The prevailing evidence suggests that immunological memory does not require antigenic re-stimulation but is maintained by low level tonic stimulation. We examined the hypothesis that stress agents contribute to tonic cellular activation and maintain immunological memory. Stimulation of monocyte-derived dendritic cells (DC) with stress agents elicits reactive oxygen species and HSP70. NFκB is activated, which up-regulates membrane-associated (ma) IL-15, caspase-1 and IL-1β. Co-culture of stress-treated DC with mononuclear cells activates IL-15 and IL-1β receptors on CD4(+) T cells, eliciting CD40L, proliferation, and up-regulation of CD45RO(+) memory T cells. The transcription factors Tbet(high) and RORγt are up-regulated, whereas FoxP3 is down-regulated, resulting in enhanced Th1 and Th17 expression and the corresponding cytokines. The interaction between maIL-15 expressed by DC and IL-15R on CD4(+) T cells results in one pathway and the corresponding cells expressing IL-1β and IL1βR as a second pathway. Importantly, inhibition studies with IL-15 antibodies and IL-1βR inhibitor suggest that both pathways may be required for optimum CD4(+) CD45RO(+) memory T cell expression. Type 1 IFN expression in splenic CD11c DC of stress-treated mice demonstrated a significant increase of IFN-α in CD11c CD317(+) and CD8α(+) DC. Analysis of RNA in human CD4(+) memory T cells showed up-regulation of type 1 IFN-stimulated genes and inhibition with histone methyltransferase inhibitor. We suggest the paradigm that stress-induced tonic stimulation might be responsible for the robust persistence of the immune response in vaccination and that epigenetic changes are involved in maintaining CD4(+) T cell memory. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Synergistic Effects in Sonochemical Sterilization

    PubMed Central

    Boucher, Raymond M. G.; Pisano, Michael A.; Tortora, George; Sawicki, Edward

    1967-01-01

    The synergistic effects observed during the sterilization of Bacillus subtilis var. niger ATCC 9372 by the combined action of ethylene or propylene oxide with high-intensity airborne sound waves (34.8 kc/sec) were investigated. It has been shown that the number of surviving spores deposited on paper strips decreases exponentially with the sound intensity at sample level. Reductions of the order of one-third of the time required for standard propylene oxide sterilization have been observed by using the combined action of sound waves with gaseous sterilization. At the present time, maximal synergistic effects seem to be achieved for the following experimental conditions: propylene oxide concentration, 500 to 1,000 mg/liter; acoustic intensity, 161 to 162 db; contact time, 80 min; temperature, 60 C; and relative humidity, 40%. The basic mechanism involved in sonochemical sterilization seems to be more of a physical (accelerated gas diffusion) than a chemical nature. PMID:4965941

  14. A PORTABLE DENTAL STERILIZING CYLINDER

    DTIC Science & Technology

    The report describes an aluminum cylinder in which dental instruments could be sterilized under emergency field conditions and at the same time be...protected against corrosion. The procedure involves loading the cylinder with dental instruments, flushing it with ethylene oxide-Freon gas, closing it...and then immersing it in boiling water for l hour. In preliminary experiments with a prototype of the sterilizing cylinder, dental instruments were

  15. Sterilization 1. The changing attitude.

    PubMed

    Teper, S

    1977-01-01

    Since the end of World War 2 in the U.S., there has been a marked change in attitude towards and treatment of the mentally handicapped, and the result - in terms of sterilization - is that many States no longer use their compulsory sterilization laws and some have repealed them. In any event, the incidence of compulsory sterilization has decreased markedly. Yet, in the past decade there have been occasional attempts to resort to the procedure for punitive reasons. These efforts have generally involved women with illegitimate children who are supported by welfare payments. Over the same decade there has been in the U.S. a remarkable growth in the use of voluntary and contraceptive sterilization as the means of preventing additional children. Preliminary results from the national Survey of Family Growth 1973 revealed that 29% of couples between the ages of 15 and 44 years who did not want more children were sterilized - males and females about equally. In Britain the development of sterilization has followed a somewhat different path. During the 1st decades of the 20th century the people in Britain were very concerned about the extensiveness of mental subnormality in the population and with the care of this group. In 1930 the Eugenics society made its 1st formal statement on the use of sterilization, advocating its use for those individuals who might transmit severe physical or mental defects which might affect the health of their progeny. More evidence was determined needed before there would be an attempt made to initiate legislation, and no legislation was ever effected. Also, from 1925 onwards, there was a debate in medical and legal circles on the consequences for patients and doctors of sterilizing operations and on the risks of litigation in the criminal and civil courts. The most marked change came in 1972 when the National Health Service (Family Planning) Act empowered local authorities to provide facilities for vasectomy on the same basis as other

  16. 21 CFR 880.6880 - Steam sterilizer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Steam sterilizer. 880.6880 Section 880.6880 Food... § 880.6880 Steam sterilizer. (a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam....

  17. 21 CFR 880.6880 - Steam sterilizer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Steam sterilizer. 880.6880 Section 880.6880 Food... § 880.6880 Steam sterilizer. (a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam....

  18. 21 CFR 880.6880 - Steam sterilizer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Steam sterilizer. 880.6880 Section 880.6880 Food... § 880.6880 Steam sterilizer. (a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam....

  19. 21 CFR 880.6880 - Steam sterilizer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Steam sterilizer. 880.6880 Section 880.6880 Food... § 880.6880 Steam sterilizer. (a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam....

  20. 21 CFR 880.6880 - Steam sterilizer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Steam sterilizer. 880.6880 Section 880.6880 Food... § 880.6880 Steam sterilizer. (a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam....

  1. Radiation sterilization of skin allograft

    NASA Astrophysics Data System (ADS)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  2. Sterilization of soybean powder with plasma treatment in atmospheric humid air

    NASA Astrophysics Data System (ADS)

    Iwami, R.; Kikuchi, Y.; Fukumoto, N.; Nagata, M.; Nakayama, A.; Nakagawa, K.

    2013-10-01

    Sterilization of foods has been performed by conventional methods such as heat, steam and chemical solutions. However, these sterilization techniques could cause damages to the food material. It is considered that plasma sterilization at atmospheric pressure is one of the promising alternative methods because of the low temperature process. In our previous study, the inactivation of Bacillus atrophaeusspores by a dielectric barrier discharge (DBD) plasma produced in atmospheric humid air was investigated in order to develop low-temperature, low-cost and high-speed plasma sterilization technique. The results showed that the inactivation of Bacillus atrophaeusspores was found to be dependent strongly on the humidity. In the present study, the plasma treatment technique in humid air is applied to sterilization of soybean powder. Effects of plasma sterilization were successfully confirmed by a colony counting method. It was found that the sterilization efficiency was increased by using the humid air as the discharge gas. In the conference, an improvement of the plasma treatment system to enhance the sterilization efficiency will be shown.

  3. Costs of low-temperature plasma sterilization compared with other sterilization methods.

    PubMed

    Adler, S; Scherrer, M; Daschner, F D

    1998-10-01

    Plasma sterilization is a new technique for decontaminating thermolabile products without the severe drawbacks associated with gas sterilization methods (residues, environment compatibility). The actual costs, per sterilization unit, of three sterilization techniques--plasma, ethylene oxide and formaldehyde--were compared. As plasma sterilization is an alternative to steam sterilization for sterilizing thermostable but easily corroding products or electronic instruments, costs for steam sterilization were calculated and compared as well. If one considers only the cost of the sterilization procedure itself, without taking into account the time-saving element of plasma sterilization, then ethylene oxide sterilization proves to be the most expensive procedure, followed by plasma sterilization; sterilization with formaldehyde was the least expensive. Inclusion of the time required to sterilize an instruments, however, altered the relative costs of the three methods. Because plasma sterilization takes less time to perform than either ethylene oxide or formaldehyde sterilization, fewer instruments need be procured. In order to measure and compare the time-saving advantage that plasma sterilization affords, five groups of instruments were assembled and the total cost of sterilizing an instrument of each group was calculated. The five groups included (1) disposable, (2) electronic, (3) endoscopic, (4) sharp and (5) standard instruments. In all cases, ethylene oxide sterilization was the most expensive method. Formaldehyde sterilization was, in four out of five cases, more expensive than plasma sterilization. Steam sterilization proved to be the cheapest method of sterilizing a laparoscopic set, even when costs due to damage inflicted on the optical instruments were calculated. In the case of a vitrectome, however, plasma sterilization costs were nearly the same as steam sterilization when the lower rate of damage by plasma sterilization was taken into account.

  4. Genomic Networks of Hybrid Sterility

    PubMed Central

    Turner, Leslie M.; White, Michael A.; Tautz, Diethard; Payseur, Bret A.

    2014-01-01

    Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci (“Dobzhansky-Muller incompatibilities”). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL—but not cis eQTL—were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is

  5. Characterization of Prdm9 in equids and sterility in mules.

    PubMed

    Steiner, Cynthia C; Ryder, Oliver A

    2013-01-01

    Prdm9 (Meisetz) is the first speciation gene discovered in vertebrates conferring reproductive isolation. This locus encodes a meiosis-specific histone H3 methyltransferase that specifies meiotic recombination hotspots during gametogenesis. Allelic differences in Prdm9, characterized for a variable number of zinc finger (ZF) domains, have been associated with hybrid sterility in male house mice via spermatogenic failure at the pachytene stage. The mule, a classic example of hybrid sterility in mammals also exhibits a similar spermatogenesis breakdown, making Prdm9 an interesting candidate to evaluate in equine hybrids. In this study, we characterized the Prdm9 gene in all species of equids by analyzing sequence variation of the ZF domains and estimating positive selection. We also evaluated the role of Prdm9 in hybrid sterility by assessing allelic differences of ZF domains in equine hybrids. We found remarkable variation in the sequence and number of ZF domains among equid species, ranging from five domains in the Tibetan kiang and Asiatic wild ass, to 14 in the Grevy's zebra. Positive selection was detected in all species at amino acid sites known to be associated with DNA-binding specificity of ZF domains in mice and humans. Equine hybrids, in particular a quartet pedigree composed of a fertile mule showed a mosaic of sequences and number of ZF domains suggesting that Prdm9 variation does not seem by itself to contribute to equine hybrid sterility.

  6. Characterization of Prdm9 in Equids and Sterility in Mules

    PubMed Central

    Steiner, Cynthia C.; Ryder, Oliver A.

    2013-01-01

    Prdm9 (Meisetz) is the first speciation gene discovered in vertebrates conferring reproductive isolation. This locus encodes a meiosis-specific histone H3 methyltransferase that specifies meiotic recombination hotspots during gametogenesis. Allelic differences in Prdm9, characterized for a variable number of zinc finger (ZF) domains, have been associated with hybrid sterility in male house mice via spermatogenic failure at the pachytene stage. The mule, a classic example of hybrid sterility in mammals also exhibits a similar spermatogenesis breakdown, making Prdm9 an interesting candidate to evaluate in equine hybrids. In this study, we characterized the Prdm9 gene in all species of equids by analyzing sequence variation of the ZF domains and estimating positive selection. We also evaluated the role of Prdm9 in hybrid sterility by assessing allelic differences of ZF domains in equine hybrids. We found remarkable variation in the sequence and number of ZF domains among equid species, ranging from five domains in the Tibetan kiang and Asiatic wild ass, to 14 in the Grevy’s zebra. Positive selection was detected in all species at amino acid sites known to be associated with DNA-binding specificity of ZF domains in mice and humans. Equine hybrids, in particular a quartet pedigree composed of a fertile mule showed a mosaic of sequences and number of ZF domains suggesting that Prdm9 variation does not seem by itself to contribute to equine hybrid sterility. PMID:23613924

  7. The limits of sterility assurance.

    PubMed

    von Woedtke, Thomas; Kramer, Axel

    2008-09-03

    Sterility means the absence of all viable microorganisms including viruses. At present, a sterility assurance level (SAL) of 10(-6) is generally accepted for pharmacopoeial sterilization procedures, i.e., a probability of not more than one viable microorganism in an amount of one million sterilised items of the final product. By extrapolating the reduction rates following extreme artificial initial contamination, a theoretical overall performance of the procedure of at least 12 lg increments (overkill conditions) is demanded to verify an SAL of 10(-6). By comparison, other recommendations for thermal sterilization procedures demand only evidence that the difference between the initial contamination and the number of test organisms at the end of the process amount to more than six orders of magnitude. However, a practical proof of the required level of sterility assurance of 10(-6) is not possible. Moreover, the attainability of this condition is fundamentally dubious, at least in non-thermal procedures. Thus, the question is discussed whether the undifferentiated adherence to the concept of sterility assurance on the basis of a single SAL of 10(-6) corresponds with the safety requirements in terms of patient or user safety, costs and energy efficiency. Therefore, in terms of practical considerations, a concept of tiered SALs is recommended, analogous to the comparable and well-established categorization into "High-level disinfection", "Intermediate-level disinfection" and "Low-level disinfection". The determination of such tiered SALs is geared both to the intended application of the sterilized goods, as well as to the characteristics of the products and the corresponding treatment options.In the case of aseptic preparation, filling and production procedures, a mean contamination probability of 10(-3) is assumed. In automated processes, lower contamination rates can be realized. In the case of the production of re-usable medical devices, a reduction of at least 2

  8. Bacterial Sterilization Using Cavitating Jet

    NASA Astrophysics Data System (ADS)

    Azuma, Yohei; Kato, Hiroharu; Usami, Ron; Fukushima, Tadamasa

    In this paper, a new sterilization method using cavitating flow is presented. Water with bacteria was pressurized up to 105 MPa and flushed out through two very small nozzles 0.1-0.31 mm in diameter, where a cavitating jet was generated containing bubbles that collapsed downstream. First, the effects of jet velocity and cavitation number on the sterilization rate of Escherichia coli JCM1649T (E. coli) were examined. The sterilization rate increased with jet velocity. The rate was proportional to the 3rd power of the velocity. All the E. coli cells were killed by three successive treatments at V=355.7 m/s and cavitation number σ=0.154. The sterilization rate has a peak depending on cavitation number at the low-jet-velocity region of less than 300 m/s. An experiment was also performed to compare two types of bacteria, E. coli, as typical Gram-negative bacteria and Bacillus subtilis JCM1465T (B. subtilis), as typical Gram-positive bacteria. Additional tests were performed using Pseudomonas putida JCM13063T, Gram-negative bacteria and Bacillus halodurans JCTM9153, Gram-positive bacteria. The sterilization rate of the Gram-positive bacteria was much lower than that of the Gram-negative bacteria under the same experimental conditions. Gram-positive bacteria have a thicker peptidoglycan layer than Gram-negative bacteria. This may be the reason why B. subtilis is more resistant to the mechanical stress caused by cavitating flow.

  9. Are all sterilization processes alike?

    PubMed

    Muscarella, L F

    1998-05-01

    Automated processes designed to sterilize reusable medical instruments use heat and low-temperature chemicals. Several factors, including the physical properties of the sterilizing agents and whether all of the instruments' surfaces can be adequately cleaned, can cause significant variations in the reliability and effectiveness of the sterilization processes. Instruments exposed to heat-based sterilization processes pose the lowest probability of transmitting diseases between patients. Heat can conduct through many different types of materials and can destroy microorganisms embedded under layers of patient debris. Studies have demonstrated, however, that--unlike heat--low-temperature chemicals require direct contact with the microorganisms to be effective. Moreover, the complex designs of some instruments can adversely affect the low-temperature sterilization processes' outcomes by hindering cleaning and preventing the flow of low-temperature chemicals to all of the instruments' contaminated surfaces. This article will explore the differences between heat-based and low-temperature chemical processes to help health care providers minimize the risk of cross-infection.

  10. Sterile versus non-sterile glove use and aseptic technique.

    PubMed

    Flores, Ashley

    There is evidence indicating that improvements in infection control practice can reduce the incidence of healthcare-associated infection. This article explores the evidence base for glove use and aseptic technique. There is a lack of evidence regarding the influence of sterile versus clean gloves in clinical care. Therefore in practice, clean and aseptic techniques are often used interchangeably. Nurses must learn to select clean or aseptic technique, and therefore clean or sterile gloves, using a risk assessment protocol. Regular audits of aseptic technique and education are needed to improve care.

  11. Review of Sterilization Techniques and Clinical Updates.

    PubMed

    Clark, Nisse V; Endicott, Scott P; Jorgensen, Elisa M; Hur, Hye-Chun; Lockrow, Ernest G; Kern, Mary E; Jones-Cox, Candice E; Dunlow, Susan G; Einarsson, Jon I; Cohen, Sarah L

    2017-09-19

    Sterilization is the most common form of contraception used worldwide and is highly effective in preventing unintended pregnancy. Several sterilization methods exist, each with unique advantages and disadvantages that influence the preferred approach for an individual patient. Salpingectomy for sterilization has popularized in recent years with mounting evidence suggesting a protective effect against ovarian cancers that originate from the fallopian tube. At the same time, Essure® hysteroscopic sterilization has come under scrutiny due to increasing reports of adverse effects that may be related to the device. This paper reviews clinical updates in sterilization, with a focus on salpingectomy and Essure hysteroscopic sterilization. Copyright © 2017. Published by Elsevier Inc.

  12. Cytoplasmic Sterility Factors in VICIA FABA L

    PubMed Central

    Edwardson, J. R.; Bond, D. A.; Christie, R. G.

    1976-01-01

    Tissues of cytoplasmic male sterile, maintainer, restorer, and restored lines, and sterile plants which reverted to fertility in Vicia faba were examined in ultrathin sections. Cytoplasmic spherical bodies (CSB), ca. 70 nm in diameter, were observed in tissues of all sterile plants but not in tissues of maintainer, restorer or restored sterile plants. No CSB were observed in a reverted fertile branch of a tiller-sterile plant, nor in 5 of 6 reverted fertile plants. One reverted fertile plant contained CSB in ovules. It is proposed that the CSB are the sites of, or possibly, products of, sterility factors in Vicia faba. PMID:17248701

  13. Portable Ethylene Oxide Sterilization Chamber

    PubMed Central

    Songer, J. R.; Mathis, R. G.

    1969-01-01

    A portable ethylene oxide sterilization chamber was designed, constructed, and tested for use in the sterilization of embolectomy catheters. The unit can accommodate catheters up to 40 inches (101.6 cm) in length and can be operated for less than 4 cents per cycle. A constant concentration of 500 mg of ethylene oxide per liter of space and holding periods of 4 and 6 hr at 43 and 22 C, respectively, were adequate when tested with B. subtilis spores. The estimated cost of construction was $165.00. If temperature control is unnecessary, the cost is approximately $80.00. Images PMID:4977644

  14. Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia.

    PubMed

    Molanouri Shamsi, M; Chekachak, S; Soudi, S; Quinn, L S; Ranjbar, K; Chenari, J; Yazdi, M H; Mahdavi, M

    2017-02-01

    Cancer cachexia is characterized by inflammation, loss of skeletal muscle and adipose tissue mass, and functional impairment. Oxidative stress and inflammation are believed to regulate pathways controlling skeletal muscle wasting. The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation, on expression of IL-15 and inflammatory cytokines in 4T1 breast cancer-bearing mice with cachexia. Selenium nanoparticle supplementation accelerated cachexia symptoms in tumor-bearing mice, while exercise training prevented muscle wasting in tumor-bearing mice. Also, aerobic interval training enhanced the anti-inflammatory indices IL-10/TNF-α ratio and IL-15 expression in skeletal muscle in tumor-bearing mice. However, combining exercise training and antioxidant supplementation prevented cachexia and muscle wasting and additionally decreased tumor volume in 4T1 breast cancer mice. These finding suggested that combining exercise training and antioxidant supplementation could be a strategy for managing tumor volume and preventing cachexia in breast cancer.

  15. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

    PubMed Central

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

    2015-01-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  16. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs.

    PubMed

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P; Esteves, Pedro J

    2015-11-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. © The Author(s) 2015.

  17. Transgenic technologies to induce sterility.

    PubMed

    Catteruccia, Flaminia; Crisanti, Andrea; Wimmer, Ernst A

    2009-11-16

    The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes.

  18. Sterile Neutrino Search with MINOS

    SciTech Connect

    Devan, Alena V.

    2015-08-01

    MINOS, Main Injector Neutrino Oscillation Search, is a long-baseline neutrino oscillation experiment in the NuMI muon neutrino beam at the Fermi National Accelerator Laboratory in Batavia, IL. It consists of two detectors, a near detector positioned 1 km from the source of the beam and a far detector 734 km away in Minnesota. MINOS is primarily designed to observe muon neutrino disappearance resulting from three flavor oscillations. The Standard Model of Particle Physics predicts that neutrinos oscillate between three active flavors as they propagate through space. This means that a muon-type neutrino has a certain probability to later interact as a different type of neutrino. In the standard picture, the neutrino oscillation probabilities depend only on three neutrino flavors and two mass splittings, Δm2. An anomaly was observed by the LSND and MiniBooNE experiments that suggests the existence of a fourth, sterile neutrino flavor that does not interact through any of the known Standard Model interactions. Oscillations into a theoretical sterile flavor may be observed by a deficit in neutral current interactions in the MINOS detectors. A distortion in the charged current energy spectrum might also be visible if oscillations into the sterile flavor are driven by a large mass-squared difference, ms2 ~ 1 eV2. The results of the 2013 sterile neutrino search are presented here.

  19. Radappertization (Radiation Sterilization) of Foods

    DTIC Science & Technology

    1976-12-01

    Street, Westport, c·r 06880; 1974. S-78-P EVALUATION OF THE TINPLATE CONTAINER FOR PACKAGING OF IRRADIA- TION STERILIZED FOODS. J. J. Killoran, E... TINPLATE CAN FOR PACKAGING OF RADAPPERTIZED BEEF UNDER PRODUCTION CONDITIONS. J. J. Killoran, J. J. Hawker, and E. Wierbicki. 5-12𔄂-P RELIABILITY OF

  20. Firebreak Maintenance With Soil Sterilants

    Treesearch

    James K. Brown

    1966-01-01

    In 1959 and 1962 the Minnesota Division of Forestry and the North Central Forest Experiment Station established a series of tests to determine the effectiveness of several herbicides in maintaining firebreaks free of vegetation. The primary objectives of these tests were to determine: (1) how long one application of soil sterilant can keep firebreaks satisfactorily...

  1. Microwave powered sterile access port

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L. (Inventor); Atwater, James E. (Inventor); Dahl, Roger W. (Inventor); Garmon, Frank C. (Inventor); Lunsford, Teddie D. (Inventor); Michalek, William F. (Inventor); Wheeler, Jr., Richard R. (Inventor)

    2000-01-01

    A device and method for elimination of contamination during transfer of materials either into or from bioreactors, food containers, or other microbially vulnerable systems. Using microwave power, thermal sterilizations of mating fixtures are achieved simply, reliably, and quickly by the volatilization of small quantities of water to produce superheated steam which contacts all exposed surfaces.

  2. Sterile pyuria: a forgotten entity

    PubMed Central

    Persad, Raj

    2015-01-01

    Sterile pyuria is a common entity. Yet there are no guidelines to address this issue. We have conducted a systematic review over 20 years and reviewed the results. Guidelines for assessment, diagnosis and management are developed based on these results. PMID:26425144

  3. Sterilization of Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Elkins, Thomas E.; Andersen, H. Frank

    1992-01-01

    This article examines the historical, legal, and ethical concerns regarding sterilization for persons with mental retardation and offers guidelines to help counsel individuals with disabilities or their families regarding decision making about sterilization. (DB)

  4. Sterilization beneath rings on dental instruments.

    PubMed

    Miller, C H; Sheldrake, M A

    1991-12-01

    This study determined the effectiveness of standard methods of instrument sterilization beneath instrument rings. Sets of three types of dental instruments were contaminated with known amounts of bacterial spores (Bacillus stearothermophilus or Bacillus subtilis). Instrument rings were placed over the contamination and the instruments processed through standard cycles in a steam autoclave, an unsaturated chemical vapor sterilizer, a standard dry heat sterilizer, an ethylene oxide gas sterilizer or a 2.0% alkaline glutaraldehyde solution. Controls consisted of spore-contaminated instruments without rings that were not processed through any sterilizing method and that were processed through each sterilizing method. All instruments and their associated rings were cultured for the presence of live spores. The results indicate that the reliability of sterilization beneath the instrument rings used is greatest if the ringed instruments are processed through a steam autoclave or an unsaturated chemical vapor sterilizer.

  5. The limits of sterility assurance

    PubMed Central

    von Woedtke, Thomas; Kramer, Axel

    2008-01-01

    Sterility means the absence of all viable microorganisms including viruses. At present, a sterility assurance level (SAL) of 10–6 is generally accepted for pharmacopoeial sterilization procedures, i.e., a probability of not more than one viable microorganism in an amount of one million sterilised items of the final product. By extrapolating the reduction rates following extreme artificial initial contamination, a theoretical overall performance of the procedure of at least 12 lg increments (overkill conditions) is demanded to verify an SAL of 10–6. By comparison, other recommendations for thermal sterilization procedures demand only evidence that the difference between the initial contamination and the number of test organisms at the end of the process amount to more than six orders of magnitude. However, a practical proof of the required level of sterility assurance of 10–6 is not possible. Moreover, the attainability of this condition is fundamentally dubious, at least in non-thermal procedures. Thus, the question is discussed whether the undifferentiated adherence to the concept of sterility assurance on the basis of a single SAL of 10–6 corresponds with the safety requirements in terms of patient or user safety, costs and energy efficiency. Therefore, in terms of practical considerations, a concept of tiered SALs is recommended, analogous to the comparable and well-established categorization into “High-level disinfection”, “Intermediate-level disinfection” and “Low-level disinfection”. The determination of such tiered SALs is geared both to the intended application of the sterilized goods, as well as to the characteristics of the products and the corresponding treatment options. In the case of aseptic preparation, filling and production procedures, a mean contamination probability of 10–3 is assumed. In automated processes, lower contamination rates can be realized. In the case of the production of re-usable medical devices, a reduction of

  6. Sterile neutrinos at the CNGS

    NASA Astrophysics Data System (ADS)

    Donini, Andrea; Maltoni, Michele; Meloni, Davide; Migliozzi, Pasquale; Terranova, Francesco

    2007-12-01

    We study the potential of the CNGS beam in constraining the parameter space of a model with one sterile neutrino separated from three active ones by an Script O(eV2) mass-squared difference, Δ mSBL2. We perform our analysis using the OPERA detector as a reference (our analysis can be upgraded including a detailed simulation of the ICARUS detector). We point out that the channel with the largest potential to constrain the sterile neutrino parameter space at the CNGS beam is νμ→ντ. The reason for that is twofold: first, the active-sterile mixing angle that governs this oscillation is the less constrained by present experiments; second, this is the signal for which both OPERA and ICARUS have been designed, and thus benefits from an extremely low background. In our analysis we also took into account νμ→νe oscillations. We find that the CNGS potential to look for sterile neutrinos is limited with nominal intensity of the beam, but it is significantly enhanced with a factor 2 to 10 increase in the neutrino flux. Data from both channels allow us, in this case, to constrain further the four-neutrino model parameter space. Our results hold for any value of Δ mSBL2gtrsim0.1 eV2, i.e. when oscillations driven by this mass-squared difference are averaged. We have also checked that the bound on θ13 that can be put at the CNGS is not affected by the possible existence of sterile neutrinos.

  7. Reionization in sterile neutrino cosmologies

    NASA Astrophysics Data System (ADS)

    Bose, Sownak; Frenk, Carlos S.; Hou, Jun; Lacey, Cedric G.; Lovell, Mark R.

    2016-12-01

    We investigate the process of reionization in a model in which the dark matter is a warm elementary particle such as a sterile neutrino. We focus on models that are consistent with the dark matter decay interpretation of the recently detected line at 3.5 keV in the X-ray spectra of galaxies and clusters. In warm dark matter models, the primordial spectrum of density perturbations has a cut-off on the scale of dwarf galaxies. Structure formation therefore begins later than in the standard cold dark matter (CDM) model and very few objects form below the cut-off mass scale. To calculate the number of ionizing photons, we use the Durham semi-analytic model of galaxy formation, GALFORM. We find that even the most extreme 7 keV sterile neutrino we consider is able to reionize the Universe early enough to be compatible with the bounds on the epoch of reionization from Planck. This, perhaps surprising, result arises from the rapid build-up of high redshift galaxies in the sterile neutrino models which is also reflected in a faster evolution of their far-UV luminosity function between 10 > z > 7 than in CDM. The dominant sources of ionizing photons are systematically more massive in the sterile neutrino models than in CDM. As a consistency check on the models, we calculate the present-day luminosity function of satellites of Milky Way-like galaxies. When the satellites recently discovered in the Dark Energy Survey are taken into account, strong constraints are placed on viable sterile neutrino models.

  8. Plasma Sterilization Technology for Spacecraft Applications

    NASA Technical Reports Server (NTRS)

    Fraser, S. J.; Olson, R. L.; Leavens, W. M.

    1975-01-01

    The application of plasma gas technology to sterilization and decontamination of spacecraft components is considered. Areas investigated include: effective sterilizing ranges of four separate gases; lethal constituents of a plasma environment; effectiveness of plasma against a diverse group of microorganisms; penetrating efficiency of plasmas for sterilization; and compatibility of spacecraft materials with plasma environments. Results demonstrated that plasma gas, specifically helium plasma, is a highly effective sterilant and is compatible with spacecraft materials.

  9. New developments in disinfection and sterilization.

    PubMed

    Wallace, Craig A

    2016-05-02

    A review of regulatory clearances for selected new sterilization and disinfection products for the period January 2012-June 2015 indicates continued leverage of established technologies for steam and low-temperature sterilization, and high-level disinfection. New products in these areas were typically modified and improved versions of existing products, with the exception of a new combination hydrogen peroxide/ozone sterilizer. Development of new low-temperature sterilization technologies to address continued evolution of complex medical devices is expected to continue.

  10. Assessment of Residual Moisture and Maintenance of Sterility in Surgical Instrument Sets after Sterilization.

    PubMed

    Fayard, Camille; Lambert, Christophe; Guimier-Pingault, Catherine; Levast, Marion; Germi, Raphaelle

    2015-08-01

    Good sterilization practices include discarding items containing residual moisture after steam sterilization. In this small laboratory study, however, the presence of residual water did not appear to compromise the sterility of surgical instruments in 2 commonly used types of packaging during routine storage after steam sterilization.

  11. 45 CFR 96.73 - Sterilization.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Sterilization. 96.73 Section 96.73 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Social Services Block Grants § 96.73 Sterilization. If a State authorizes sterilization as a family planning service, it must comply...

  12. 45 CFR 96.73 - Sterilization.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Sterilization. 96.73 Section 96.73 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Social Services Block Grants § 96.73 Sterilization. If a State authorizes sterilization as a family planning service, it must comply...

  13. Microwave Sterilization and Depyrogenation System

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Dahl, Roger W.; Wheeler, Richard R., Jr.

    2009-01-01

    A fully functional, microgravity-compatible microwave sterilization and depyrogenation system (MSDS) prototype was developed that is capable of producing medical-grade water (MGW) without expendable supplies, using NASA potable water that currently is available aboard the International Space Station (ISS) and will be available for Lunar and planetary missions in the future. The microwave- based, continuous MSDS efficiently couples microwaves to a single-phase, pressurized, flowing water stream that is rapidly heated above 150 C. Under these conditions, water is rapidly sterilized. Endotoxins, significant biological toxins that originate from the cell walls of gram-negative bacteria and which represent another defining MGW requirement, are also deactivated (i.e., depyrogenated) albeit more slowly, with such deactivation representing a more difficult challenge than sterilization. Several innovations culminated in the successful MSDS prototype design. The most significant is the antenna-directed microwave heating of a water stream flowing through a microwave sterilization chamber (MSC). Novel antenna designs were developed to increase microwave transmission efficiency. These improvements resulted in greater than 95-percent absorption of incident microwaves. In addition, incorporation of recuperative heat exchangers (RHxs) in the design reduced the microwave power required to heat a water stream flowing at 15 mL/min to 170 C to only 50 W. Further improvements in energy efficiency involved the employment of a second antenna to redirect reflected microwaves back into the MSC, eliminating the need for a water load and simplifying MSDS design. A quick connect (QC) is another innovation that can be sterilized and depyrogenated at temperature, and then cooled using a unique flow design, allowing collection of MGW at atmospheric pressure and 80 C. The final innovation was the use of in-line mixers incorporated in the flow path to disrupt laminar flow and increase contact time

  14. Conference Planning.

    ERIC Educational Resources Information Center

    Burke, W. Warner, Ed.; Beckhard, Richard, Ed.

    This book, written to instruct in the use of a conference as a medium of social intercourse, is divided into four sections. Section I, which contains five articles, deals with factors to be considered in planning a conference. Specific techniques one can employ to improve a conference and several different techniques for evaluating the…

  15. Effect of Tubal Sterilization Technique on Risk of Serous Ovarian and Primary Peritoneal Carcinoma

    PubMed Central

    LESSARD-ANDERSON, Collette R.; HANDLOGTEN, Kathryn S.; MOLITOR, Rochelle J.; DOWDY, Sean C.; CLIBY, William A.; WEAVER, Amy L.; SAUVER, Jennifer ST.; BAKKUM-GAMEZ, Jamie N.

    2014-01-01

    Objective To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC). Methods We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity. Results In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29–1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13–1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization. Conclusions We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods. PMID:25316178

  16. Birth Control, Sterilization and Abortion

    PubMed Central

    Schneiderman, Lawrence J.; Prichard, Lorraine; Fuller, Scott; Atkinson, Leslie

    1974-01-01

    A questionnaire comprising case histories was administered to 27 Protestant and 27 Catholic clergymen in the San Diego area to test their attitudes toward the use of birth control, sterilization and abortion in families with specific genetic problems. The responses indicated: • Catholic and Protestant clergymen do not always follow the official positions of their churches in these matters, although the majority of them do. • Protestant clergymen were more likely to approve of birth control, sterilization, and abortion than Catholic clergymen. • The approval responses of Protestant and Catholic clergymen were not greatly influenced by whether the illness variables involved high Mendelian risk, high psychological cost, high social cost, or poor prognosis. • The approval responses of Protestant and Catholic clergymen were not significantly influenced by the socio-ethnic background of the families. PMID:4813802

  17. Counseling issues in tubal sterilization.

    PubMed

    Baill, I Cori; Cullins, Vanessa E; Pati, Sangeeta

    2003-03-15

    Female sterilization is the number one contraceptive choice among women in the United States. Counseling issues include ensuring that the woman understands the permanence of the procedure and knowing the factors that correlate with future regret. The clinician should be aware of the cumulative failure rate of the procedure, which is reported to be about 1.85 percent during a 10-year period. Complications of tubal sterilization include problems with anesthesia, hemorrhage, organ damage, and mortality. Some women who undergo tubal ligation may experience increased sexual satisfaction. While the procedure is commonly performed postpartum, it can be done readily, without relation to recent pregnancy, by laparoscopy or, when available, by minilaparotomy. Surgery should be timed immediately postpartum, or coincide with the first half of the woman's menstrual cycle or during a time period when the woman is using a reliable form of contraception.

  18. Implementing AORN recommended practices for sterilization.

    PubMed

    Graybill-D'Ercole, Patricia

    2013-05-01

    Any hospital or facility in which surgery and other invasive procedures are performed should have accommodations for cleaning, decontaminating, disinfecting, and sterilizing instruments, equipment, and other essential supplies that are used for patient procedures. Sterilization is essential to reducing or preventing the risk of surgical site infections. This is a collaborative process and should include all health care providers who handle these instruments, including perioperative nurses. The revised AORN "Recommended practices for sterilization," which became effective June 15, 2012, includes updates on sterilizing single-use items, inspecting critical items before sterilization, using low-temperature hydrogen peroxide vapor sterilization methods, and immediate use steam sterilization. This RP document is the first AORN document to be evidence rated and accepted for inclusion in the Agency for Healthcare Research and Quality National Guideline Clearinghouse. Copyright © 2013 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  19. Method of sterilization using ozone

    NASA Technical Reports Server (NTRS)

    Murphy, Oliver J. (Inventor); Hitchens, G. Duncan (Inventor)

    2002-01-01

    Methods of using ozone have been developed which sterilize instruments and medical wastes, oxidize, organics found in wastewater, clean laundry, break down contaminants in soil into a form more readily digested by microbes, kill microorganisms present in food products, and destroy toxins present in food products. The preferred methods for killing microorganism and destroying toxins use pressurized, humidified, and concentrated ozone produced by an electrochemical cell.

  20. Sterile Neutrinos in Cold Climates

    SciTech Connect

    Jones, Benjamin J.P.

    2015-09-01

    Measurements of neutrino oscillations at short baselines contain an intriguing set of experimental anomalies that may be suggestive of new physics such as the existence of sterile neutrinos. This three-part thesis presents research directed towards understanding these anomalies and searching for sterile neutrino oscillations. Part I contains a theoretical discussion of neutrino coherence properties. The open-quantum-system picture of neutrino beams, which allows a rigorous prediction of coherence distances for accelerator neutrinos, is presented. Validity of the standard treatment of active and sterile neutrino oscillations at short baselines is verified, and non-standard coherence loss effects at longer baselines are predicted. Part II concerns liquid argon detector development for the MicroBooNE experiment, which will search for short-baseline oscillations in the Booster Neutrino Beam at Fermilab. Topics include characterization and installation of the MicroBooNE optical system; test-stand measurements of liquid argon optical properties with dissolved impurities; optimization of wavelength-shifting coatings for liquid argon scintillation light detection; testing and deployment of high-voltage surge arrestors to protect TPC field cages; and software development for optical and TPC simulation and reconstruction. Part III presents a search for sterile neutrinos using the IceCube neutrino telescope, which has collected a large sample of atmospheric-neutrino-induced events in the 1-10 TeV energy range. Sterile neutrinos would modify the detected neutrino flux shape via MSW-resonant oscillations. Following a careful treatment of systematic uncertainties in the sample, no evidence for MSW-resonant oscillations is observed, and exclusion limits on 3+1 model parameter space are derived. Under the mixing assumptions made, the 90% confidence level exclusion limit extends to sin224 ≤ 0.02 at m2 ~ 0.3 eV2, and the LSND and Mini

  1. Observation of Effectiveness of Clinical Sterilization by CASP-80A Low-Temperature Plasma Sterilizer

    NASA Astrophysics Data System (ADS)

    Li, Si; Zhang, Yangde; Liu, Weidong

    2006-09-01

    The influence on the effectiveness of sterilization by low-temperature plasma sterilizer CASP-80A was investigated so as to provide a theoretical basis for reducing medical costs and achieving ideal sterilization effectiveness. To conduct the on-site simulation test, a clinical material sterilization test and a test of the influence of organic substance were conducted, the former by using the representative of Bacillus Stearothermophilus, preparing the bacteria-contaminated carrier through polytetrafluoroethylene (PTFE) simulated hose endoscopes, and the latter by using calf serum as the influence factor of the organic substance. The results show that the CASP-80A low-temperature plasma sterilizer could achieve effective sterilization by either the short-cycle or the long-cycle sterilization method depending on different materials, apparatus, and extent of contamination. The organic substances could influence the effectiveness of sterilization by the low-temperature plasma (H2O2) sterilizer.

  2. Plasma Sterilization: New Epoch in Medical Textiles

    NASA Astrophysics Data System (ADS)

    Senthilkumar, P.; Arun, N.; Vigneswaran, C.

    2015-04-01

    Clothing is perceived to be second skin to the human body since it is in close contact with the human skin most of the times. In hospitals, use of textile materials in different forms and sterilization of these materials is an essential requirement for preventing spread of germs. The need for appropriate disinfection and sterilization techniques is of paramount importance. There has been a continuous demand for novel sterilization techniques appropriate for use on various textile materials as the existing sterilization techniques suffer from various technical and economical drawbacks. Plasma sterilization is the alternative method, which is friendlier and more effective on the wide spectrum of prokaryotic and eukaryotic microorganisms. Basically, the main inactivation factors for cells exposed to plasma are heat, UV radiation and various reactive species. Plasma exposure can kill micro-organisms on a surface in addition to removing adsorbed monolayer of surface contaminants. Advantages of plasma surface treatment are removal of contaminants from the surface, change in the surface energy and sterilization of the surface. Plasma sterilization aims to kill and/or remove all micro-organisms which may cause infection of humans or animals, or which can cause spoilage of foods or other goods. This review paper emphasizes necessity for sterilization, essentials of sterilization, mechanism of plasma sterilization and the parameters influencing it.

  3. Comparison of liquid chemical sterilization with peracetic acid and ethylene oxide sterilization for long narrow lumens.

    PubMed

    Alfa, M J; DeGagne, P; Olson, N; Hizon, R

    1998-10-01

    The aim of this study was to determine how well peracetic acid liquid chemical sterilization (LCPAS) killed test organisms in the presence of 10% fetal bovine serum and 0.65% salt challenge (RPMI-S) compared with a 100% ethylene oxide (ETO) sterilizer and an ETO hydrochlorofluorocarbon (ETO-HCFC) sterilization method with long (125 cm), narrow (3-mm internal diameter) flexible lumens as the test carrier. The inoculated lumens were dried overnight before processing. The test organisms included Mycobacterium chelonei, Enterococcus faecalis, and Bacillus subtilis. For all 3 organisms tested, the LCPAS process resulted in a 6 log10 reduction in bacterial load compared with a 2.5 log10 to 6 log10 reduction for the 100% ETO and ETO-HCFC sterilizers. Sterilization was achieved for 100%, 61%, and 67% of the lumen test carriers for the LCPAS, 100% ETO, and ETO-HCFC sterilizers, respectively. The data indicate that of the sterilization methods evaluated, LCPAS was the most effective for sterilizing narrow flexible lumens in the presence of residual inorganic and organic soil. This effectiveness was achieved through a combination of organism wash-off and peracetic acid sterilant killing of organisms. Salt was the major compounding factor for effective ETO gas sterilization, because carriers inoculated with organisms in 10% fetal bovine serum alone all were sterilized by both 100% ETO and ETO-HCFC sterilization methods. Our data support the critical need to ensure adequate precleaning of narrow flexible lumen endoscopes before any sterilization method.

  4. Surgical sterilization, regret, and race: contemporary patterns.

    PubMed

    Shreffler, Karina M; McQuillan, Julia; Greil, Arthur L; Johnson, David R

    2015-03-01

    Surgical sterilization is a relatively permanent form of contraception that has been disproportionately used by Black, Hispanic, and Native American women in the United States in the past. We use a nationally representative sample of 4592 women ages 25-45 to determine whether sterilization continues to be more common and consequential by race for reproductive-age women. Results indicate that Native American and Black women are more likely to be sterilized than non-Hispanic White women, and Hispanic and Native American women are more likely than non-Hispanic White women to report that their sterilization surgeries prevent them from conceiving children they want. Reasons for sterilization differ significantly by race. These findings suggest that stratified reproduction has not ended in the United States and that the patterns and consequences of sterilization continue to vary by race. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

  6. Radiation sterilization of new drug delivery systems.

    PubMed

    Abuhanoğlu, Gürhan; Ozer, A Yekta

    2014-06-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation.

  7. Surgical Sterilization, Regret, and Race: Contemporary Patterns*

    PubMed Central

    Shreffler, Karina M.; McQuillan, Julia; Greil, Arthur L.; Johnson, David R.

    2014-01-01

    Surgical sterilization is a relatively permanent form of contraception that has been disproportionately used by Black, Hispanic, and Native American women in the United States in the past. We use a nationally representative sample of 4,609 women ages 25 to 45 to determine whether sterilization continues to be more common and consequential by race for reproductive-age women. Results indicate that Native American and Black women are more likely to be sterilized than non-Hispanic White women, and Hispanic and Native American women are more likely than non-Hispanic White women to report that their sterilization surgeries prevent them from conceiving children they want. Reasons for sterilization differ significantly by race. These findings suggest that stratified reproduction has not ended in the United States and that the patterns and consequences of sterilization continue to vary by race. PMID:25592919

  8. Sterilization of products contaminated with Pyronema domesticum.

    PubMed

    Lampe, Carol M; Hansen, Joyce M; Rymer, Therese M; Sargent, Harold

    2009-01-01

    Product recalls due to non-sterility occurred between 1993 and 1994 among manufacturers that were sterilizing cotton products sourced from China using ethylene oxide (EO). The primary contaminant was identified as a pyrophilous mold from the class Discomycetes, Pyronema domesticum. Multiple references suggest this organism has special needs for reproducing and maintaining the two assumed resistant stages of this organism (ascospores and sclerotia). Sterilization resistance studies were performed using a China-sourced cotton product that was naturally contaminated with P. domesticum. These studies showed the organisms to have: 1) a low resistance to moist heat sterilization at 250 degrees F (121 degrees C); a resistance to radiation no greater than that predicted by the bioburden-based resistance model (i.e., Population C) used for dose determination Method 1 described in ANSI/AAMI/ISO 11137-2:2006--Sterilization of health care products--Radiation--Part 2: Establishing the sterilization dose; and 3) a high resistance to EO processing.

  9. Hysteroscopic Sterilization: History and Current Methods

    PubMed Central

    Greenberg, James A

    2008-01-01

    For many practicing obstetrician-gynecologists, tubal ligation was the gold standard by which female sterilization techniques were measured. Yet gynecologic surgeons have simultaneously sought to occlude the fallopian tubes transcervically to avoid discomfort and complications associated with transabdominal approaches. In this review, the history of transcervical sterilization is discussed. Past, current, and upcoming techniques are reviewed. This article focuses on interval sterilization techniques, thus removing post-vaginal and post-cesarean delivery tubal ligations from the discussion. PMID:19015762

  10. Sterile neutrino dark matter with supersymmetry

    NASA Astrophysics Data System (ADS)

    Shakya, Bibhushan; Wells, James D.

    2017-08-01

    Sterile neutrino dark matter, a popular alternative to the WIMP paradigm, has generally been studied in non-supersymmetric setups. If the underlying theory is supersymmetric, we find that several interesting and novel dark matter features can arise. In particular, in scenarios of freeze-in production of sterile neutrino dark matter, its superpartner, the sterile sneutrino, can play a crucial role in early Universe cosmology as the dominant source of cold, warm, or hot dark matter, or of a subdominant relativistic population of sterile neutrinos that can contribute to the effective number of relativistic degrees of freedom Neff during big bang nucleosynthesis.

  11. The Status of Sterile Neutrino Dark Matter

    NASA Astrophysics Data System (ADS)

    Horiuchi, Shunsaku

    2017-01-01

    The sterile neutrino is a particle dark matter candidate with a host of observable signatures that is close to being fully tested. I will first review the implications for structure formation, comparing predictions of sterile neutrino cosmologies against observations. I will then review analyses of X-rays from dark matter concentrations in search of mono-energetic photons predicted from sterile neutrino dark matter decays. Structure formation and X-rays offer important complementary probes, and I will highlight the recent rapid progress in testing the sterile neutrino parameter space. I will also discuss implications of analyses leading to the detection of X-ray lines from clusters of galaxies and Andromeda.

  12. Ramifications of a sterile Mars

    NASA Astrophysics Data System (ADS)

    Levin, Gilbert V.

    2011-10-01

    The seldom considered ramifications of a sterile Mars are explored. Very much is now known about the environment on Mars. Herein, the individual and collective environmental parameters are examined with particular consideration of those that might be inimical to life as we know it, or as might reasonably be assumed to be so to alien life. It is shown that no single measurement or combination of them precludes the ability of Mars to support even a wide number of terrestrial microbial species, let alone the likely greater tolerance and/or adaptability of possible alien life forms. Some yet unknown factor or combination of factors would have to be responsible for Mars' failure to generate life or to successfully harbor viable forms received from space. Since Mars is so Earth-like, the red planet's sterility could deliver a fatal blow to the growing concept of a cosmic Biologic Imperative, and would raise the daunting prospect that Earth is a unique or a very rare habitat.

  13. Steam quality and effective sterilization.

    PubMed

    Sedlacek, R S; Rose, E F

    1985-01-01

    Faced with using steam from a commercial utility having boilers greater than 5 miles distant and being the last user on the system resulted in ineffective sterilization. A three phase testing program was established utilizing: Direct physical measurements - an Ellison model 915A portable steam calorimeter. Direct microbiology - Autoclaved feed pellets were aseptically placed in fluid thioglycolate medium and incubated at 37 degrees C. Indirect microbiology - Feces from "defined flora" mice fed the autoclaved pelleted feed were tested. Colorimetric measurements verified that the steam sometimes contained greater than 5% entrained water. During periods of wet steam it was impossible to maintain consistent sterility of the mouse pellets even using a cycle of 126 degrees C for 60 minutes. One spore-forming Gram positive rod, Clostridium perfringens type D was the predominant bacterium isolated. Lactating mice, or mice stressed experimentally came down with diarrhea within days of eating pellets treated with wet steam (calorimetric measurements) and a subsequent positive culture. These mice voided stools predominantly showing Clostridium perfringens type D.

  14. Factors Influencing the Activity of Sterile Filtered and Heat-Sterilized Trypsin Solutions

    PubMed Central

    Cook, R. A.; Poole, G. M.

    1974-01-01

    The mode of sterilization (filtration or heat) was found to significantly affect the activity of trypsin solutions. Trypsin activity was substantially reduced in the initial fractions of filtrate passed through asbestos filter pads; heat-sterilized trypsin was satisfactory for transfer of cell cultures grown on glass. Heat-sterilized trypsin may be useful when elimination of filterable organisms is required. PMID:4844278

  15. A sterile-female technique proposed for control of Striga hermonthica and other intractable weeds: Advantages, shortcomings, and risk management

    USDA-ARS?s Scientific Manuscript database

    Weeds have posed intractable challenges to farmers since the dawn of agriculture. This article describes in detail a proposed control strategy based on the introduction of genes conferring female-sterility into the genomes of intractable target weeds. Spread of these genes through target populations...

  16. 9 CFR 109.2 - Sterilizers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sterilizers. 109.2 Section 109.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STERILIZATION AND PASTEURIZATION...

  17. 9 CFR 109.2 - Sterilizers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sterilizers. 109.2 Section 109.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STERILIZATION AND PASTEURIZATION...

  18. Eugenics and Involuntary Sterilization: 1907-2015.

    PubMed

    Reilly, Philip R

    2015-01-01

    In England during the late nineteenth century, intellectuals, especially Francis Galton, called for a variety of eugenic policies aimed at ensuring the health of the human species. In the United States, members of the Progressive movement embraced eugenic ideas, especially immigration restriction and sterilization. Indiana enacted the first eugenic sterilization law in 1907, and the US Supreme Court upheld such laws in 1927. State programs targeted institutionalized, mentally disabled women. Beginning in the late 1930s, proponents rationalized involuntary sterilization as protecting vulnerable women from unwanted pregnancy. By World War II, programs in the United States had sterilized approximately 60,000 persons. After the horrific revelations concerning Nazi eugenics (German Hereditary Health Courts approved at least 400,000 sterilization operations in less than a decade), eugenic sterilization programs in the United States declined rapidly. Simplistic eugenic thinking has faded, but coerced sterilization remains widespread, especially in China and India. In many parts of the world, involuntary sterilization is still intermittently used against minority groups.

  19. An inexpensive laparoscopy system for female sterilization.

    PubMed

    Wheeless, C R

    1975-12-01

    Laparoscopy has become an established procedure for female sterilization. The cost of the equipment remains excessively high, thereby reducing its availability to all physicians and patients who desire and need it. We have described an inexpensive--but highly effective--female sterilization system utilizing equipment that should cost in the range of $400.00.

  20. 9 CFR 109.2 - Sterilizers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Sterilizers. 109.2 Section 109.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STERILIZATION AND PASTEURIZATION...

  1. 9 CFR 109.2 - Sterilizers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Sterilizers. 109.2 Section 109.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STERILIZATION AND PASTEURIZATION...

  2. 9 CFR 109.2 - Sterilizers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Sterilizers. 109.2 Section 109.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STERILIZATION AND PASTEURIZATION...

  3. Paraformaldehyde for Surface Sterilization and Detoxification

    PubMed Central

    Taylor, Larry A.; Barbeito, Manuel S.; Gremillion, Gardner G.

    1969-01-01

    Paraformaldehyde powder, depolymerized by heat, produced formaldehyde gas that was effective in sterilizing laboratory rooms, a mobile laboratory trailer, various surfaces, fiberglass filter medium, and specialized laboratory equipment. A sporulating and nonsporulating strain of bacteria, a virus, and a bacterial toxin were used as test agents. The dissemination procedures and equipment, the assay techniques, and the facilities and equipment sterilized were described. PMID:4977223

  4. Heat sterilization times of red pine boards

    Treesearch

    William T. Simpson

    2004-01-01

    The objective of this study was to determine the time required to heat the center of red pine boards to various temperatures for sterilization. This information will serve as a guideline for those concerned with heat sterilizing wood pallets and other wood shipping containers to meet heat treatment requirements for protection against invasive pests. Red pine boards, 4...

  5. Higgs production through sterile neutrinos

    NASA Astrophysics Data System (ADS)

    Antusch, Stefan; Cazzato, Eros; Fischer, Oliver

    2016-10-01

    In scenarios with sterile (right-handed) neutrinos with an approximate “lepton-number-like” symmetry, the heavy neutrinos (the mass eigenstates) can have masses around the electroweak scale and couple to the Higgs boson with, in principle, unsuppressed Yukawa couplings, while the smallness of the light neutrinos’ masses is guaranteed by the approximate symmetry. The on-shell production of the heavy neutrinos at lepton colliders, together with their subsequent decays into a light neutrino and a Higgs boson, constitutes a resonant contribution to the Higgs production mechanism. This resonant mono-Higgs production mechanism can contribute significantly to the mono-Higgs observables at future lepton colliders. A dedicated search for the heavy neutrinos in this channel exhibits sensitivities for the electron neutrino Yukawa coupling as small as ˜ 5 × 10-3. Furthermore, the sensitivity is enhanced for higher center-of-mass energies, when identical integrated luminosities are considered.

  6. Disinfection, sterilization, and antisepsis: An overview.

    PubMed

    Rutala, William A; Weber, David J

    2016-05-02

    All invasive procedures involve contact by a medical device or surgical instrument with a patient's sterile tissue or mucous membranes. The level of disinfection or sterilization is dependent on the intended use of the object: critical (items that contact sterile tissue such as surgical instruments), semicritical (items that contact mucous membrane such as endoscopes), and noncritical (devices that contact only intact skin such as stethoscopes) items require sterilization, high-level disinfection and low-level disinfection, respectively. Cleaning must always precede high-level disinfection and sterilization. Antiseptics are essential to infection prevention as part of a hand hygiene program as well as several other uses such as surgical hand antisepsis and pre-operative skin preparation.

  7. Care and sterilization of endourologic instruments.

    PubMed

    Gregory, E; Simmons, D; Weinberg, J J

    1988-08-01

    All endourologic instruments must be handled properly if they are to continue to function properly. Care must be taken in washing and sterilizing of this equipment, as not all endoscopic equipment can endure all methods, and people who are working with these instruments must be taught the proper care and sterilization methods of each. For example, fiberoptic telescopes and light cables must never be autoclaved; ethylene oxide is the method of choice. Disinfectant is an alternative. Loops, sheaths, high-frequency cables, resectoscopes, and working elements should be sterilized by ethylene oxide. Loops and high-frequency cables should not be soaked in a disinfectant, but other instruments may be soaked. All instruments should be dried before sterilization. Too much emphasis cannot be placed on the importance of proper storage of these very fragile fiberoptic instruments. With proper care and sterilization, these instruments will need fewer repairs and function properly for a longer time.

  8. Vapor Hydrogen Peroxide Sterilization Certification

    NASA Astrophysics Data System (ADS)

    Chen, Fei; Chung, Shirley; Barengoltz, Jack

    For interplanetary missions landing on a planet of potential biological interest, United States NASA planetary protection currently requires that the flight system must be assembled, tested and ultimately launched with the intent of minimizing the bioload taken to and deposited on the planet. Currently the only NASA approved microbial reduction method is dry heat sterilization process. However, with utilization of such elements as highly sophisticated electronics and sensors in modern spacecraft, this process presents significant materials challenges and is thus an undesirable bioburden reduction method to design engineers. The objective of this work is to introduce vapor hydrogen peroxide (VHP) as an alternative to dry heat microbial reduction to meet planetary protection requirements. The VHP sterilization technology is widely used by the medical industry, but high doses of VHP may degrade the performance of flight hardware, or compromise material compatibility. The goal of our study is determine the minimum VHP process conditions for PP acceptable microbial reduction levels. A series of experiments were conducted using Geobacillus stearothermophilus to determine VHP process parameters that provided significant reductions in spore viability while allowing survival of sufficient spores for statistically significant enumeration. In addition to the obvious process parameters -hydrogen peroxide concentration, number of pulses, and exposure duration -the investigation also considered the possible effect of environmental pa-rameters. Temperature, relative humidity, and material substrate effects on lethality were also studied. Based on the results, a most conservative D value was recommended. This recom-mended D value was also validated using VHP "hardy" strains that were isolated from clean-rooms and environmental populations collected from spacecraft relevant areas. The efficiency of VHP at ambient condition as well as VHP material compatibility will also be

  9. Conference Resolution

    NASA Astrophysics Data System (ADS)

    2009-04-01

    Since the first IUPAP International Conference on Women in Physics (Paris, March 2002) and the Second Conference (Rio de Janeiro, May 2005), progress has continued in most countries and world regions to attract girls to physics and advance women into leadership roles, and many working groups have formed. The Third Conference (Seoul, October 2008), with 283 attendees from 57 countries, was dedicated to celebrating the physics achievements of women throughout the world, networking toward new international collaborations, building each participant's capacity for career success, and aiding the formation of active regional working groups to advance women in physics. Despite the progress, women remain a small minority of the physics community in most countries.

  10. Identification of a mitochondrial protein associated with cytoplasmic male sterility in petunia.

    PubMed Central

    Nivison, H T; Hanson, M R

    1989-01-01

    The petunia fused gene (pcf), which is associated with cytoplasmic male sterility (CMS), is composed of sequences derived from atp9, coxII, and an unidentified reading frame termed urfS. To determine whether the pcf gene is expressed at the protein level, we produced antibodies to synthetic peptides specified by the coxII and urfS portions of the pcf gene. Anti-COXII peptide antibodies recognized petunia COXII but no other mitochondrial proteins. Anti-URF-S peptide antibodies recognized a 20-kilodalton protein present in both cytoplasmic male sterile and fertile lines and a protein with an apparent molecular mass of 25 kilodaltons present only in cytoplasmic male sterile lines. The 25-kilodalton protein was found to be synthesized by isolated mitochondria and to fractionate into both the soluble and membrane portions of disrupted mitochondria, whereas the 20-kilodalton protein was found only in the membrane fraction. The abundance of the 25-kilodalton protein was much lower in fertile plants carrying the cytoplasmic male sterile cytoplasm and a single dominant nuclear fertility restorer gene, Rf. Thus, the pcf gene is correlated with cytoplasmic male sterility not only by its co-segregation with the phenotype in somatic hybrids, but also by the modification of its expression at the protein level through the action of a nuclear gene that confers fertility. PMID:2562768

  11. Sterilization: women fit to be tied.

    PubMed

    Caress, B

    1975-01-01

    Sterilization abuse is both systematic and widespread. Frequently, women are misled about the dangers of surgery, misinformed about its permanence, and coerced while under the stress of labor or abortion. Generally, instances of abuses in the health system are treated as illegitimate, illegal aberations of an otherwise decent health care system. Careful examination of these so called abuses would reveal that each can be causally connected to particular aspects of the care of America's health system. Sterilization abuse stems from a combination of factors inherent in the health system plus 1 critical additional factor. Besides resulting from teaching and research imperatives, profit making, and the fee for service systems, such abuse is the most widespread example of medicine as an instrument of social control. Sterilization is the most extreme form of birth control and birth control is official US government policy. There were about 500,000 sterilizations performed on American women in 1973. None of the sterilization methods is innocuous, and each is associated with some physical and psychological side effects. General agreement exists in the medical literature that some risk is attendant to each procedure. Sterilization is the most dangerous and the fastest growing method of birth control. Since 1970 the figures show an almost 3-fold increase in the incidence of female sterilization, from 192,000 in 1970 to 548,000 in 1974. Much evidence exists to suggest that the increase in the number of sterilizations has fueled a trend toward the sterilization of younger women with fewer children. Official accommodation to liberalization of sterilization practices in the US came in 1969, when the American College of Obstetricians and Gynecologists (ACOG) withdrew its age parity formula. This liberalization of sterilization guidelines opened the floodgates to abuse. Some of the increase in the number of operations performed is due to increased demand, some of it is the result

  12. Biomedical Conferences

    NASA Technical Reports Server (NTRS)

    1976-01-01

    As a result of Biomedical Conferences, Vivo Metric Systems Co. has produced cardiac electrodes based on NASA technology. Frequently in science, one highly specialized discipline is unaware of relevant advances made in other areas. In an attempt to familiarize researchers in a variety of disciplines with medical problems and needs, NASA has sponsored conferences that bring together university scientists, practicing physicians and manufacturers of medical instruments.

  13. Hysteroscopic placement of tubal sterilization implants: virtual reality simulator training.

    PubMed

    Panel, Pierre; Bajka, Michael; Le Tohic, Arnaud; Ghoneimi, Alaa El; Chis, Carmen; Cotin, Stéphane

    2012-07-01

    To assess face and construct validity of a new virtual reality (VR) training simulator for hysteroscopic placement of tubal sterilization implants. Nonrandomized, controlled trial comparing responses and performance of novices and experts on the simulator. Canadian task force II-1. Forty-six gynecologists were personally invited or recruited at the 33rd Conference of the French National College of Gynecologists and Obstetricians (CNGOF) from December 9 to 12, 2009, grouped as 20 experts and 26 novices. They all performed the defined sequence of virtual procedures on the simulator (case 1 for familiarization, case 4 for study assessment) and finally completed the study questionnaire. Responses to realism, educational potential, and general opinion were excellent, proving face validity. Significant differences between novices and experts were assessed for 7 of the 15 metrics analyzed, proving construct validity. We established face and construct validity for EssureSim, an educational VR simulator for hysteroscopic tubal sterilization implant placement. The next steps are to investigate convergent and predictive validity to affirm the real capacity of transferring the skills learned on the training simulator to the patient in the operating room.

  14. Problems in sterilization of unmanned space vehicles.

    PubMed

    Jaffe, L D

    1964-01-01

    The probability of achieving and maintaining sterility of an unmanned spacecraft with varied suggested procedures is examined in detail, as are alternative techniques for avoiding biological contamination of the planets. The required degree of assurance against contamination of Mars, Venus and the Moon with Earth organisms is also considered. For Mars landers and orbiters, sterilization of the spacecraft or capsule by dry heat, with no subsequent access, is found to be desirable. For the present, sterilization of Venus landers still seems desirable. For Mars flybys, and for Venus orbiters and flybys, control of the trajectory to minimize the chance of unintentionally entering the planetary atmosphere appears the method of choice. For the Moon, sterilization seems unnecessary, but microbial counts should be kept low. Sterilization lowers spacecraft and system reliability. It reduces the chance of launching within periods fixed by astronomical constraints and increases costs. The gain which should be achieved through spacecraft sterilization, in return of significant biological information about the planets, must be balanced against these losses. In particular, one should keep in mind the loss in return of biological data occasioned by failure of a spacecraft to fulfill its mission; the probability of such failure is increased by sterilization.

  15. Characteristics of Surface Sterilization using ECR Plasma

    NASA Astrophysics Data System (ADS)

    Yonesu, Akira; Hara, Kazufumi; Nishikawa, Tatsuya; Hayashi, Nobuya

    2015-09-01

    Plasma sterilization techniques have superior characteristics such as a short treatment times, non-toxicity and low thermal damages on the sterilized materials. In plasma sterilization, microorganisms can be sterilized by active radicals, energetic charged particles, and vacuum UV radiation. The influence of each factor depends on the plasma operating parameters. Microwave discharges under the electron cyclotron resonance (ECR) condition produce higher electron temperature and density plasma as compared with other plasma generation techniques. In the present study, characteristics of surface sterilization using ECR plasma have been investigated.The experiment was performed in the vacuum chamber which contains a magnet holder. A pair of rectangular Sm-Co permanent magnets is aligned parallel to each other within the magnet holder. The region of the magnetic field for ECR exists near the magnet holder surface. When the microwave is introduced into the vacuum chamber, a ECR plasma is produced around surface of the magnet holder. High energy electrons and oxygen radicals were observed at ECR zone by electric probe method and optical spectroscopic method. Biological indicators (B.I.) having spore of 106 was sterilized in 2min for oxygen discharge. The temperature of the B.I. installation position was about 55°. The sterilization was achieved by the effect of oxygen radicals and high energy electrons.

  16. Parameters governing steam sterilization of deadlegs.

    PubMed

    Young, J H; Ferko, B L; Gaber, R P

    1994-01-01

    Use of saturated steam for sterilization-in-place (SIP) is limited by factors effecting displacement of air from deadlegs. Effects of tube diameter, length, orientation and position within a deadleg were quantitatively studied by examining temperature profiles and rates of kill of Bacillus stearothermophilus spores. Tube diameter had the greatest effect on sterilization. For small diameter tubes, 0.4 cm inside diameter (ID), air displacement was minimal and due mainly to diffusion. 8.8 cm long tubes with 0.4 cm IDs could not be sterilized at 121 degrees C. As tube diameter was increased and buoyant driven convective flow became dominant over viscous forces, sterilization was achieved and tube orientation became critical. Sterilization time, as defined by a twelve log reduction in spore population, was 75 minutes in a 19.0 cm long vertical tube with 1.7 cm ID, whereas 167 minutes were required for an 8.8 cm long tube with 1.0 cm ID. For 8.8 cm long tubes, only the 1.7 cm ID tube could be sterilized when orientated 5 degrees above horizontal. Data show that length to diameter ratios, L/Ds, do not provide a general guideline which can be used to predict sterilization. In the absence of steam bleeders, equipment should be designed to assure strong buoyancy driven convective flow to assure adequate air removal. This requires elimination of small diameter deadlegs (0.4 cm ID and less) and vertical positioning of deadlegs.

  17. New sterilization technologies alternative to ethylene oxide

    NASA Astrophysics Data System (ADS)

    Tabrizian, Maryam; Lerouge, Sophie; Debrie, Anne; Yahia, L'Hocine

    1997-06-01

    Sterilization of biomedical devices may induce bulk and surface modification, responsible for the decrease or loss of their biofunctionality. Pure ethylene oxide (EO) at low temperature and new alternative techniques such as cold gas plasma sterilization have been developed for heat-sensitive polymers. There is a lack of the knowledge concerning their safety in terms of materials damage and consequences on the biofunctionality of sterilized devices. The objective of our work consists in studying bulk and surface changes in biomedical devices induced by these two sterilization techniques. Samples from PVC, Polyurethane, Polyacrylate and Polyethylene-based medical devices are subjected to 1, 5, and 10 sterilization cycles by Steri-Vac-3M (pure EO), Sterrad-100$TM, J&J (gas plasma + H2O2), and studied by X-rays photoelectron spectroscopy. Preliminary results show an increasing in Oxygen/Carbon ratio by a factor of 1.3 to 4.4 between the first and tenth cycle indicating the surface oxidation by gas plasma sterilization processes. Some changes in C-C chemical bounding are associated with EO sterilization.

  18. An investigation of a sterile access technique for the repair and adjustment of sterile spacecraft

    NASA Technical Reports Server (NTRS)

    Farmer, F. H.; Fuller, H. V.; Hueschen, R. M.

    1973-01-01

    A description is presented of a unique system for the sterilization and sterile repair of spacecraft and the results of a test program designed to assess the biological integrity and engineering reliability of the system. This trailer-mounted system, designated the model assembly sterilizer for testing (MAST), is capable of the dry-heat sterilization of spacecraft and/or components less than 2.3 meters in diameter at temperatures up to 433 K and the steam sterilization of components less than 0.724 meter in diameter. Sterile access to spacecraft is provided by two tunnel suits, called the bioisolator suit systems (BISS), which are contiguous with the walls of the sterilization chambers. The test program was designed primarily to verify the biological and engineering reliability of the MAST system by processing simulated space hardware. Each test cycle simulated the initial sterilization of a spacecraft, sterile repair of a failed component, removal of the spacecraft from the MAST for mating with the bus, and a sterile recycle repair.

  19. The efficacy of low temperature plasma (LTP) sterilization, a new sterilization technique.

    PubMed

    Höller, C; Martiny, H; Christiansen, B; Rüden, H; Gundermann, K O

    1993-07-01

    The efficacy of low temperature plasma (LTP) sterilization, a newly developed sterilization procedure was tested. Following experiments were carried out: Determination of the most resistant test organism, influence of 10% and 20% defibrinated sheep blood or varying salt concentrations on the efficacy of the sterilization process, influence of the carrier position in the sterilization chamber and in the sterilization pouches, influence of a loaded sterilization chamber, comparative efficacy of EO and LTP, steel carriers with a blood burden of 0%, 5% and 10%, comparative efficacy of EO and LTP, strip carriers in endoscopes, blood burden 0% and 10%, with and without adaptors, evaluation of two bioindicator models. B. pumilus was the test spore that overall seemed to be most resistant to the sterilization procedure. Supplementation of the test suspension with blood or saline crystals resulted in significantly reduced efficacy and has to be avoided in practical operation. The fully loaded sterilization chamber or the position of germ carriers on the shelves had no negative influence on the effectivity of the sterilization process. There were no significant differences between EO and LTP, the blood burden not exceeding 5%. 10% blood burden resulted in a significantly weaker action of LTP. For sterilization of long lumens adaptors containing hydrogen peroxide are necessary. An appropriate bioindicator tube model is introduced.

  20. Complications of female sterilization: immediate and delayed.

    PubMed

    Huggins, G R; Sondheimer, S J

    1984-03-01

    Surgical sterilization in women has changed dramatically over the past 20 years. The development of laparoscopy and minilaparotomy have made the procedure readily available even in developing countries. In the United States, changing social values and changes in hospital regulations have done as much as technology to account for the tremendous increases in the number of women undergoing sterilization. Improved sterilization procedures have resulted in lower costs for sterilization and lowered morbidity and mortality rates. Hysterectomy for sterilization alone carries unacceptable morbidity and mortality rates. Originally, laparoscopic techniques utilized unipolar cautery. However, bowel burns, a rare but serious complication, were reported, and this led to newer techniques. These techniques, using bands, clips, and bipolar cautery, have gained increasing popularity and have eliminated many of the serious complications of female sterilization. Historically, there has been concern that tubal sterilization by any method produces, in significant numbers of patients, the subsequent gynecologic and psychologic problems called "post-tubal ligation syndrome." A review of earlier literature indicates that many of these studies have serious methodologic problems, including recall bias, inappropriate control groups, failure to elicit prior history of gynecologic or psychologic problems, and failure to account for the use of oral contraceptives or IUDs. More recent large prospective epidemiologic studies that have controlled for prior gynecologic problems and contraceptive usage have failed to show increased incidence of gynecologic sequelae in large numbers of women. However, there are some data to support the concept that in certain individuals, sterilization may result in disruption of ovarian blood or nerve supply, producing gynecologic sequelae. Additional data from these ongoing large-scale studies and others should help to elucidate this problem in the future. Pregnancy

  1. Chemical sterilization of allograft dermal tissues.

    PubMed

    Phipps, Abigail; Vaynshteyn, Edward; Kowalski, John B; Ngo, Manh-Dan; Merritt, Karen; Osborne, Joel; Chnari, Evangelia

    2017-08-10

    Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10(-6). Microbiological performance qualification demonstrated a complete kill of 10(6) spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10(-6), and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

  2. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: an observational cohort study

    PubMed Central

    Mao, Jialin; Pfeifer, Samantha; Schlegel, Peter

    2015-01-01

    Objective To compare the safety and efficacy of hysteroscopic sterilization with the “Essure” device with laparoscopic sterilization in a large, all-inclusive, state cohort. Design Population based cohort study. Settings Outpatient interventional setting in New York State. Participants Women undergoing interval sterilization procedure, including hysteroscopic sterilization with Essure device and laparoscopic surgery, between 2005 and 2013. Main outcomes measures Safety events within 30 days of procedures; unintended pregnancies and reoperations within one year of procedures. Mixed model accounting for hospital clustering was used to compare 30 day and 1 year outcomes, adjusting for patient characteristics and other confounders. Time to reoperation was evaluated using frailty model for time to event analysis. Results We identified 8048 patients undergoing hysteroscopic sterilization and 44 278 undergoing laparoscopic sterilization between 2005 and 2013 in New York State. There was a significant increase in the use of hysteroscopic procedures during this period, while use of laparoscopic sterilization decreased. Patients undergoing hysteroscopic sterilization were older than those undergoing laparoscopic sterilization and were more likely to have a history of pelvic inflammatory disease (10.3% v 7.2%, P<0.01), major abdominal surgery (9.4% v 7.9%, P<0.01), and cesarean section (23.2% v 15.4%, P<0.01). At one year after surgery, hysteroscopic sterilization was not associated with a higher risk of unintended pregnancy (odds ratio 0.84 (95% CI 0.63 to 1.12)) but was associated with a substantially increased risk of reoperation (odds ratio 10.16 (7.47 to 13.81)) compared with laparoscopic sterilization. Conclusions Patients undergoing hysteroscopic sterilization have a similar risk of unintended pregnancy but a more than 10-fold higher risk of undergoing reoperation compared with patients undergoing laparoscopic sterilization. Benefits and risks of both procedures

  3. Relationship between lumen diameter and length sterilized in the 125L ozone sterilizer.

    PubMed

    Dufresne, Sylvie; Leblond, Hélène; Chaunet, Marc

    2008-05-01

    A safe alternative to ethylene oxide for reprocessing heat-sensitive lumen medical devices, such as endoscopes, is needed. The effectiveness of a new, safe, low-cost, and environmentally friendly low-temperature sterilization process using ozone was assessed. Rigid lumen devices were used to assess the maximum length of lumens of different internal diameters that can be sterilized in the TSO(3) model 125L ozone sterilizer. Two inoculation techniques were used. An inoculated wire was placed inside lumens with internal diameters of 0.8 mm and larger, whereas lumens with an internal diameter of 0.5 mm were inoculated directly. Lumens with internal diameters of 0.5 mm, 1 mm, 2 mm, 3 mm, and 4 mm with lengths varying between 45 and 70 cm can be sterilized with ozone. Calculation of the log reduction value for each size demonstrated the achievement of a sterility assurance level of 10(-6). Experimental results demonstrated a linear relationship (with r(2) = 0.990) between the length of lumen that can be sterilized in the 125L ozone sterilizer and its internal diameter. Effective sterilization of an ACMI ureteroscope that is more challenging in terms of sterilant penetration in a small lumen (0.8 mm) compared with the stated lumen claims confirms that the relationship can conservatively be used to predict the length of a lumen device that can be sterilized in the 125L ozone sterilizer for a given diameter. Intermediate sizes of lumen devices that can be sterilized in the 125L ozone sterilizer can be interpolated from the linear relationship between diameter and length found in the present study.

  4. Microscope sterility during spine surgery.

    PubMed

    Bible, Jesse E; O'Neill, Kevin R; Crosby, Colin G; Schoenecker, Jonathan G; McGirt, Matthew J; Devin, Clinton J

    2012-04-01

    Prospective study. Assess the contamination rates of sterile microscope drapes after spine surgery. The use of the operating microscope has become more prevalent in certain spine procedures, providing superior magnification, visualization, and illumination of the operative field. However, it may represent an additional source of bacterial contamination and increase the risk of developing a postoperative infection. This study included 25 surgical spine cases performed by a single spine surgeon that required the use of the operative microscope. Sterile culture swabs were used to obtain samples from 7 defined locations on the microscope drape after its use during the operation. The undraped technician's console was sampled in each case as a positive control, and an additional 25 microscope drapes were swabbed immediately after they were applied to the microscope to obtain negative controls. Swab samples were assessed for bacterial growth on 5% sheep blood Columbia agar plates using a semiquantitative technique. No growth was observed on any of the 25 negative control drapes. In contrast, 100% of preoperative and 96% of postoperative positive controls demonstrated obvious contamination. In the postoperative group, all 7 sites of evaluation were found to be contaminated with rates of 12% to 44%. Four of the 7 evaluated locations were found to have significant contamination rates compared with negative controls, including the shafts of the optic eyepieces on the main surgeon side (24%, P = 0.022), "forehead" portion on both the main surgeon (24%, P = 0.022) and assistant sides (28%, P = 0.010), and "overhead" portion of the drape (44%, P = 0.0002). Bacterial contamination of the operative microscope was found to be significant after spine surgery. Contamination was more common around the optic eyepieces, likely due to inadvertent touching of unsterile portions. Similarly, all regions above the eyepieces also have a propensity for contamination because of unknown contact

  5. Access to postpartum sterilization in southeast Brazil.

    PubMed

    Janowitz, B; Higgins, J E; Clopton, D C; Nakamura, M S; Brown, M L

    1982-05-01

    All women hospitalized for delivery over a ten-week period at the largest maternity hospital in Campinas in the State of São Paulo, Brazil, were questioned about their interest in and plans for sterilization. Results from a categorical data analysis indicate that among the study variables, cesarean delivery was the necessary condition for postpartum sterilization and was significantly associated with the patient's ability to pay for services. Further, the variability in the proportion of women sterilized postpartum was almost perfectly explained by a linear model with main effects for parity and for the patient's ability to pay for services.

  6. Basics of sterile compounding: bubble point testing.

    PubMed

    Thoma, Laura

    2014-01-01

    Compounding pharmacies that compound sterile preparations must choose sterile filters that are approved for human use. They may rely on the filter manufacturer's Certificate of Quality to ensure the sterile filter is pyrogen free and has been tested for bacterial retention. The Certificate of Quality from the filter manufacturer also contains other useful information about the filter such as: flow rate and maximum pressure drop, thermal and hydraulic stress, and membrane results of the initial integrity test performed on the filter membrane with water, if a hydrophilic membrane. This article discusses the integrity test, which is often called the water bubble point test.

  7. Spore-Forming Bacteria that Resist Sterilization

    NASA Technical Reports Server (NTRS)

    LaDuc, Myron; Venkateswaran, Kasthuri

    2003-01-01

    A report presents a phenotypic and genotypic characterization of a bacterial species that has been found to be of the genus Bacillus and has been tentatively named B. odysseensis because it was isolated from surfaces of the Mars Odyssey spacecraft as part of continuing research on techniques for sterilizing spacecraft to prevent contamination of remote planets by terrestrial species. B. odysseensis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium that forms round spores. The exosporium has been conjectured to play a role in the elevated resistance to sterilization. Research on the exosporium is proposed as a path toward improved means of sterilization, medical treatment, and prevention of biofouling.

  8. Observations on female sterilization in Chile.

    PubMed

    Menanteau-Horta, D

    1982-01-01

    Prior to 1976, voluntary female sterilization was 1 of the regular family planning services offered in Chile. After that the Ministry of Public Health declared that it could not be considered a fertility regulation activity and could thus be performed only for health reasons. Between 1971-75, there was almost a 6-fold increase in the number of sterilizations performed at the Valdivia Regional Hospital, with a rise to 2400 procedures. Such an unprecedented increase in voluntary sterilization prompted this study. The results are based on a 1976 survey of women sterilized between 1971-75 at the Valdivia Regional Hospital. Personal interviews were conducted. The number of voluntary sterilizations there during the aforementioned period showed a sustained upward trend; the number of births increased only moderately during that time. The data on sterilization in the Valdivia area is compared to that collected by the Santiago study. Age, marital status, place of origin or residence, education, and religion were compared. Socioeconomic and occupational data were also examined. 9 of 10 women in Valdivia were from low-income families. This agrees closely with the Santiago data. About 1/4 of the women in both samples were employed outside the home. Also in both samples, about 1/2 of the spouses of sterilized women were blue collar workers; only 1/5 or less were white collar, and very few were professionals. About 52% in Valdivia and 45% in Santiago had borne 7 or more viable offspring. The average number of spontaneous abortions was also similar. A significantly higher percentage (P0.01) of Valdivia women used contraceptives. There are some general trends apparent in both groups as to the reasons for sterilization; most were prompted by difficult socioeconomic conditions. 37.9% of the Santiago women felt their families were complete and 27.3% of the other group cited the same reason. Other reasons were medical, failure of contraception, problems with spouse, and other. Medical

  9. Understanding current steam sterilization recommendations and guidelines.

    PubMed

    Spry, Cynthia

    2008-10-01

    Processing surgical instruments in preparation for surgery is a complex multistep practice. It is impractical to culture each and every item to determine sterility; therefore, the best assurance of a sterile product is careful execution of every step in the process coupled with an ongoing quality control program. Perioperative staff nurses and managers responsible for instrument processing, whether for a single instrument or multiple sets, must be knowledgeable with regard to cleaning; packaging; cycle selection; and the use of physical, chemical, and biological monitors. Nurses also should be able to resolve issues related to loaner sets, flash sterilization, and extended cycles.

  10. Sterile post-traumatic immunosuppression

    PubMed Central

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-01-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

  11. [Positive and negative aspects of Fallopian tube sterilization as viewed by sterilized women

    PubMed

    Minella

    1998-03-30

    The objective of this paper is to point out the positive and negative aspects of female sterilization as seen by two groups of sterilized women in Florianópolis, Santa Catarina, Brazil, based on a sociological discussion of their present health status, evaluating the associations that they generally make with the fact that they have been sterilized. The first group included mostly housewives from a low-income neighborhood, while the second involved upper-middle-class female public employees, students, and university professors, totaling 40 women. Data were obtained through a structured questionnaire with open-ended questions. Information on social, economic, and demographic variables was recorded, along with subjective data associated with women's representations of the post-sterilization period. We concluded that there was no consensus as to the consequences of sterilization, since a number of the women (11/40), mostly sterilized before the age of 30, perceived changes in their health status after surgery.

  12. Risk of wound and pelvic infection after laparoscopic tubal sterilization: instrument disinfection versus sterilization.

    PubMed

    Huezo, C M; DeStefano, F; Rubin, G L; Ory, H W

    1983-05-01

    To determine if disinfection, rather than sterilization, of laparoscopic equipment leads to an increase in the risk of postlaparoscopy infection, the authors analyzed data from a multicenter prospective study conducted by the Centers for Disease Control on the safety of sterilizing operations. From September 1978 through July 1981, 3903 women underwent laparoscopic tubal sterilization procedures in which the equipment was sterilized with ethylene oxide (58%) or disinfected with glutaraldehyde (42%). The overall risk of wound infection in each group was 1.5 per 100 women. The relative risk of wound infection for disinfection versus sterilization of the equipment was 0.5 when adjusted for differences in the two groups. The corresponding relative risk of pelvic infection was 1.2. These results suggest that laparoscopy equipment disinfected with glutaraldehyde is not associated with an increased risk of wound or pelvic infection compared with equipment sterilized with ethylene oxide.

  13. Evaluation removes obstacles to sterilization in Brazil.

    PubMed

    1985-01-01

    In 1978, Centro de Pesquisas de Assitencia Integrada a Mulher e a Crianca (CPAIMC) in Rio de Janeiro began to offer interval sterilizations in an attempt to increase the access of poor women to sterilization services. By the end of 1984, the program had provided in excess of 19,000 sterilizations, making CPAIMC Brazil's largest single source of voluntary interval sterilization. Despite the program's success, CPAIMC was concerned that obstacles still existed in the poor woman's path to sterilization access. A study was conducted by Family Health International (FHI) in collaboration with the Pathfinder Fund and CPAIMC's Department of Information, Evaluation and Research to locate possible barriers. The study indicated that less than half of the women who requested sterilization between June 1 and August 31, 1983 actually had the procedure. During that period, 1256 women requested sterilization at the CPAIMC clinic. Of these, 925 were approved, and 639 were scheduled for surgery. Only 559 were actually sterilized within 3 months of receiving approval. 1 possible reason why women were not receiving the surgery was that the women requesting sterilization actually were not highly motivated to obtain the service. Yet, study results indicate this probably was not the reason. During initial interviews at the clinic, many women said they had thought very carefully about being sterilized, and more than 40% reported deciding to have a tubal ligation before their last pregnancy. Almost 3/4 of the women reported that they did not plan their last pregnancy, and almost 2/3 indicated that the pregnancy was unwanted. About 63% were contracepting, and many were using effective methods. More than half of the non-contraceptors were not using a method because they had just ended a pregnancy and were not sexually active. As a group, the women requesting sterilization were highly motivated to avoid having more children. Age and number of children were the most important criteria used by

  14. Low-temperature sterilization and new technologies.

    PubMed

    Goveia, Vania Regina; Pinheiro, Silma Maria Cunha; Graziano, Kazuko Uchikawa

    2007-01-01

    The new low-temperature sterilization technologies are presented as an alternative to the use of ethylene oxide. This review was performed in order to identify evidences of the antimicrobial activity, toxicity, adverse events and the applicability of these technologies. The research was carried through the electronic databases MEDLINE and LILACS up to 2005. The authors analyzed 10 articles in this survey. The studies about the efficacy of these sterilization methods constitute experimental and comparative research that showed the influence of the extension and diameter of the lumen, besides the presence of crystal salts. Thus, choosing the correct equipment is essential, as well as the assurance of the cleansing of the devices, which interfere with the effectiveness of the low-temperature sterilization. These technologies present limitations regarding the sterilization of graft bone and affect the materials properties.

  15. Ethylene oxide sterilization: the way ahead.

    PubMed

    Peacock, R

    1999-01-01

    Despite many predictions about the demise of ethylene oxide as a sterilization method, it continues to be used for increasing volumes of medical devices. This article examines why this has happened and what the future holds.

  16. Gamma-ray irradiation, autoclave and ethylene oxide sterilization to thermosetting polyurethane: Sterilization to polyurethane

    NASA Astrophysics Data System (ADS)

    Hirata, Noriko; Matsumoto, Ken-Ichi; Inishita, Takashi; Takenaka, Yoshinori; Suma, Yasunori; Shintani, Hideharu

    1995-09-01

    Thermosetting polyurethane (PU) is widely used in a large variety of medical devices. 4,4'-methylenedianiline (MDA) was produced from PU by sterilization and it was studied for the relationship between urethane components or polymer characteristics and formation of MDA upon sterilization, using the commercially available dialyzers fabricated with different combination of isocyanate and polyol. We confirmed that the molecular-weight of polyol influenced the production of MDA upon sterilization.

  17. Cosmological and astrophysical implications of sterile neutrinos

    NASA Astrophysics Data System (ADS)

    Petraki, Kalliopi

    The discovery of neutrino masses suggests that the Standard Model should be supplemented with new gauge-singlet fermions, often called sterile neutrinos. The interplay among the new couplings introduced in the Standard Model can accommodate the neutrino oscillation data for a variety of choices: the new particles can be extremely heavy and practically unobservable, or they can be light, in which case they can solve several long-standing puzzles. It has been shown, for example, that sterile neutrinos in some range of masses can account for dark matter, their emission from a supernova can explain pulsar kicks, arid their decays can play an important role in the formation of the first stars. Though indirect, these clues indicate that sterile neutrinos can be the minimal solution to a variety of unsolved problems. This emphasizes the importance of investigating further the consequences of these new degrees of freedom for cosmology and astrophysics. In this dissertation, I explore the possible role of sterile neutrinos of different mass scales in some cosmological and astrophysical phenomena. A minimal extension of the Higgs sector of the Standard Model, with a gauge- singlet boson coupled to sterile neutrinos, can provide a consistent framework for the theory of neutrino masses, and can produce a relic population of keV sterile neutrinos via decays of the singlet Higgs. The latter can account for the dark matter of the universe. The mechanism operates around the electroweak scale, and has interesting consequences for the electroweak phase transition. Relic sterile neutrinos produced via decays at the electroweak scale constitute colder dark matter than those produced via other previously suggested mechanisms. The primordial thermal content of dark matter has important implications for the formation of cosmic structures, such as clusters and galaxies. The assessment of the relevant properties suggests that sterile neutrinos produced at the electroweak scale are a

  18. Standard aeration for gas-sterilized plastics.

    PubMed Central

    White, J. D.

    1977-01-01

    In an effort to provide guidelines for standardizing aeration times for plastics sterilized with ethylene oxide, an Aeration Index has been developed. Based on the rate of diffusion of ethylene oxide in selected polymers, the Index provides an indication of the aeration time at ambient temperature (23 degrees C) for the ethylene oxide concentration in freshly sterilized plastics to drop to 50 parts/10(6). PMID:269198

  19. Ethylene Oxide Gas Sterilization of Medical Devices.

    PubMed

    Shintani, Hideharu

    2017-01-01

     Ethylene oxide gas is an agent in the sterilization of medical devices due to its effectiveness and compatibility with most materials. The advantages and disadvantages, as well as its recommended uses, are explored in this review article. The variables and their relevance on process optimization are described, the types of processing cycles are detailed and emphasis is given to the design and validation of the sterilization process.

  20. [Experimental tests of a microwave sterilization system].

    PubMed

    Rosaspina, S; Liguori, G; Anzanel, D; Finzi, G; Salvatorelli, G

    1994-01-01

    Data obtained in our experiments indicate that the microwave sterilization system utilized may be considered as a practical and rapid method for decontaminating steel surgical instruments. For the tested organisms (7 Gram- and 2 Gram+ genera) a 3' exposure time to microwaves provides successful sterilization. Microwave irradiation also had a killing action against Bacillus subtilis spores. A study by SEM of microwave treated spores shows typical morphological alterations of spore surfaces.

  1. Low-energy sterile neutrinos: Theory

    NASA Astrophysics Data System (ADS)

    Palazzo, Antonio

    2013-04-01

    Several experimental anomalies seem to point towards the existence of light sterile neutrinos. We focus on the low-energy anomalous results (the so-called gallium and reactor anomalies), which indicate a non-zero admixture U of the electron neutrino with a fourth (mostly) sterile mass eigenstate ν4. We point out that solar sector data, in combination with the precision measurement of θ13, provide the constraint |<0.041 (90% C.L.), independent of the reactor flux determinations.

  2. Experimental Study of Sterilizing Molds by Ultrasound

    NASA Astrophysics Data System (ADS)

    Ren, Jin-lian; Niu, Yong

    1998-02-01

    An ultrasound method of sterilizing aspergillus flavus and fusarium is proposed and demonstrated. The dependence of sterilizing effect on ultrasonic intensity, frequency, and treatment time is experimentally investigated. The density of surviving spores decreases first with increasing ultrasonic frequency and then increases with the further increase of the frequency, that is to say, there exists the optimum frequency 26 kHz at which the killing rate is near 100%. The killing rate seems proportional to the intensity and the time.

  3. Methods of Sterilization and Monitoring of Sterilization AcrossSelected Dental Practices in Karachi, Pakistan.

    PubMed

    Ahmed, Hina

    2015-10-01

    To assess methods of sterilization in dental practices in Karachi and secondly to investigate methods of monitoring sterilization in dental practices in Karachi, Pakistan. Cross-sectional, descriptive study. Dental colleges, hospitals and private clinics of Karachi, Pakistan, from January to March 2013. A total of 251 questionnaires were obtained. Descriptive statistics were computed and differences between groups were assessed through chi-square test using Statistical Package for the Social Sciences (SPSS) version 16.0. P-value < 0.05 was taken as statistically significant. Autoclave, used by 155 (61.8%) dentists was the most common method of sterilization followed by more than one method, 65 (25.9%); dry heat, 24 (9.6%); and cold sterilization, 7 (2.8%). Majority of dentists, 126 (50.1%), never monitored sterilization and those who did monitored mostly monthly. Statistically significant difference was found amongst the three groups of dentists monitoring sterilization (p=0.09) and methods of sterilization (p < 0.01). Statistically significant difference was found in infection control practices of specialists, postgraduate trainees and general dentists regarding method of monitoring sterilization with majority of dentists never monitoring sterilization.

  4. 21 CFR 880.6870 - Dry-heat sterilizer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dry-heat sterilizer. 880.6870 Section 880.6870... Devices § 880.6870 Dry-heat sterilizer. (a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat....

  5. 21 CFR 872.6730 - Endodontic dry heat sterilizer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endodontic dry heat sterilizer. 872.6730 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6730 Endodontic dry heat sterilizer. (a) Identification. An endodontic dry heat sterilizer is a device intended to sterilize endodontic...

  6. 21 CFR 522.44 - Sterile sodium acetazolamide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile sodium acetazolamide. 522.44 Section 522....44 Sterile sodium acetazolamide. (a) Specifications. Sterile sodium acetazolamide contains acetazolamide sodium complying with United States Pharmacopeia as a sterile powder with directions...

  7. 21 CFR 522.44 - Sterile sodium acetazolamide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sterile sodium acetazolamide. 522.44 Section 522....44 Sterile sodium acetazolamide. (a) Specifications. Sterile sodium acetazolamide contains acetazolamide sodium complying with United States Pharmacopeia as a sterile powder with directions...

  8. [Low-temperature sterilization for the surgical infection prophylaxis].

    PubMed

    Kornev, I I; Baranov, G A; Ul'ianov, V I

    2011-01-01

    The comparative characteristic of the accepted methods of low-temperature sterilization of medical equipment is given. Special attention is devoted to the surgical infection prophylaxis. The efficacy, expediency and safety of gas sterilization with ethilenoxide is proved. Plasmic methods of sterilization is recommended for use together with other methods of low-temperature sterilization.

  9. 21 CFR 880.6870 - Dry-heat sterilizer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dry-heat sterilizer. 880.6870 Section 880.6870... Devices § 880.6870 Dry-heat sterilizer. (a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat. (b...

  10. 21 CFR 872.6730 - Endodontic dry heat sterilizer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endodontic dry heat sterilizer. 872.6730 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6730 Endodontic dry heat sterilizer. (a) Identification. An endodontic dry heat sterilizer is a device intended to sterilize endodontic...

  11. 21 CFR 872.6730 - Endodontic dry heat sterilizer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endodontic dry heat sterilizer. 872.6730 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6730 Endodontic dry heat sterilizer. (a) Identification. An endodontic dry heat sterilizer is a device intended to sterilize endodontic...

  12. 21 CFR 872.6730 - Endodontic dry heat sterilizer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endodontic dry heat sterilizer. 872.6730 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6730 Endodontic dry heat sterilizer. (a) Identification. An endodontic dry heat sterilizer is a device intended to sterilize endodontic...

  13. 21 CFR 880.6870 - Dry-heat sterilizer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dry-heat sterilizer. 880.6870 Section 880.6870... Devices § 880.6870 Dry-heat sterilizer. (a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat. (b...

  14. 21 CFR 880.6870 - Dry-heat sterilizer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dry-heat sterilizer. 880.6870 Section 880.6870... Devices § 880.6870 Dry-heat sterilizer. (a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat. (b...

  15. 21 CFR 880.6870 - Dry-heat sterilizer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dry-heat sterilizer. 880.6870 Section 880.6870... Devices § 880.6870 Dry-heat sterilizer. (a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat. (b...

  16. 21 CFR 872.6730 - Endodontic dry heat sterilizer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endodontic dry heat sterilizer. 872.6730 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6730 Endodontic dry heat sterilizer. (a) Identification. An endodontic dry heat sterilizer is a device intended to sterilize endodontic...

  17. Sterile neutrinos facing kaon physics experiments

    NASA Astrophysics Data System (ADS)

    Abada, A.; Bečirević, D.; Sumensari, O.; Weiland, C.; Funchal, R. Zukanovich

    2017-04-01

    We discuss weak kaon decays in a scenario in which the Standard Model is extended by massive sterile fermions. After revisiting the analytical expressions for leptonic and semileptonic decays we derive the expressions for decay rates with two neutrinos in the final state. By using a simple effective model with only one sterile neutrino, compatible with all current experimental bounds and general theoretical constraints, we conduct a thorough numerical analysis which reveals that the impact of the presence of massive sterile neutrinos on kaon weak decays is very small, less than 1% on decay rates. The only exception is B (KL→ν ν ) , which can go up to O (10-10), thus possibly within the reach of the KOTO, NA62 and SHIP experiments. Plans have also been proposed to search for this decay at the NA64 experiment. In other words, if all the future measurements of weak kaon decays turn out to be compatible with the Standard Model predictions, this will not rule out the existence of massive light sterile neutrinos with non-negligible active-sterile mixing. Instead, for a sterile neutrino of mass below mK, one might obtain a huge enhancement of B (KL→ν ν ), otherwise negligibly small in the Standard Model.

  18. Sterilization chosen by 11 million Americans.

    PubMed

    1979-12-01

    Nearly 11 million Americans have chosen surgical sterilization as their contraceptive method; about 1,131,000 procedures were obtained in 1978, 670,000 women and 461,000 men. In 1960 the ratio of male to female sterilizations was 40% to 60%. In 1969 The Association for Voluntary Sterilization (AVS) opened the first vasectomy clinic in the U.S. at the Margaret Sanger Center, New York City. During 1970-71 more vasectomy clinics were established around the country. The medical profession began to provide vasectomy as an office procedure. The peak of the vasectomy movement occurred in 1971 when 6700,000 vasectomies were performed. Newer techniques for female sterilization appeared, minilap and laparotomy, which required less hospitalization and facilitated quicker recovery. It is unrealistic to expect sterilization to become the number 1 method for people who are under 29 or 30. The sterilization boom has peaked, and although the numbers of acceptors has increased every year since the 1960's, the level of growth has reached a plateau.

  19. Performance evaluation of solar water sterilization system

    SciTech Connect

    Saitoh, Takeo; El-Ghetany, H.H.

    1998-07-01

    In most countries, the contaminated water is the major cause of most of the water-born diseases. Solar energy can be used in this field because the inactivation of micro-organisms is done by the ultraviolet solar radiation. A pilot solar system for sterilizing the contaminated water is designed, constructed and tested. The experimental data showed good viability for using solar energy in the sterilization process. A mathematical model of the solar sterilizer is also presented. The governing equations are solved numerically using fourth-order Runge-Kutta method. The effects of environmental conditions (ambient temperature, wind speed and solar radiation) on the solar sterilizer performance are examined. It is found that the system is affected by the ambient temperature, wind speed, ultraviolet solar radiation intensity, level of contamination of water, quantity of water being exposed, contact area between the transparent water container in the solar sterilizer and absorber plate and system geometrical parameters. It is pointed that, for a partial cloud condition, low ambient temperature and high wind speed the thermal efficiency of the solar sterilizer was minimum.

  20. Health technology assessment: Off-site sterilization

    PubMed Central

    Dehnavieh, Reza; Mirshekari, Nadia; Ghasemi, Sara; Goudarzi, Reza; Haghdoost, AliAkbar; Mehrolhassani, Mohammad Hossain; Moshkani, Zahra; Noori Hekmat, Somayeh

    2016-01-01

    Background: Every year millions of dollars are expended to equip and maintain the hospital sterilization centers, and our country is not an exception of this matter. According to this, it is important to use more effective technologies and methods in health system in order to reach more effectiveness and saving in costs. This study was conducted with the aim of evaluating the technology of regional sterilization centers. Methods: This study was done in four steps. At the first step, safety and effectiveness of technology was studied via systematic study of evidence. The next step was done to evaluate the economical aspect of off-site sterilization technology using gathered data from systematic review of the texts which were related to the technology and costs of off-site and in-site hospital sterilization. Third step was conducted to collect experiences of using technology in some selected hospitals around the world. And in the last step different aspects of acceptance and use of this technology in Iran were evaluated. Results: Review of the selected articles indicated that efficacy and effectiveness of this technology is Confirmed. The results also showed that using this method is not economical in Iran. Conclusion: According to the revealed evidences and also cost analysis, due to shortage of necessary substructures and economical aspect, installing the off-site sterilization health technology in hospitals is not possible currently. But this method can be used to provide sterilization services for clinics and outpatients centers. PMID:27390714

  1. Health technology assessment: Off-site sterilization.

    PubMed

    Dehnavieh, Reza; Mirshekari, Nadia; Ghasemi, Sara; Goudarzi, Reza; Haghdoost, AliAkbar; Mehrolhassani, Mohammad Hossain; Moshkani, Zahra; Noori Hekmat, Somayeh

    2016-01-01

    Every year millions of dollars are expended to equip and maintain the hospital sterilization centers, and our country is not an exception of this matter. According to this, it is important to use more effective technologies and methods in health system in order to reach more effectiveness and saving in costs. This study was conducted with the aim of evaluating the technology of regional sterilization centers. This study was done in four steps. At the first step, safety and effectiveness of technology was studied via systematic study of evidence. The next step was done to evaluate the economical aspect of off-site sterilization technology using gathered data from systematic review of the texts which were related to the technology and costs of off-site and in-site hospital sterilization. Third step was conducted to collect experiences of using technology in some selected hospitals around the world. And in the last step different aspects of acceptance and use of this technology in Iran were evaluated. Review of the selected articles indicated that efficacy and effectiveness of this technology is Confirmed. The results also showed that using this method is not economical in Iran. According to the revealed evidences and also cost analysis, due to shortage of necessary substructures and economical aspect, installing the off-site sterilization health technology in hospitals is not possible currently. But this method can be used to provide sterilization services for clinics and outpatients centers.

  2. Evaluation of contemporary female sterilization methods.

    PubMed

    Brenner, W E

    1981-09-01

    Different methods of sterilization were evaluated. Laparoscopic techniques were the most satisfactory because they had lower pelvic and incision infection rates and shorter hospitalization and convalescent times than laparotomy lower pelvic infection rates than culdoscopy and culpotomy. Via laparoscopy, sterilization by coagulation and cutting, spring-loaded clips and bands was an effective, safe method. Mechanical problems with the applicator and optics and decreased visibility resulted in more technical failures and difficulties and more misapplication with the clip applicator. Although the total complication rates were similar with all methods, bleeding from the tubes and wound and pelvic infections were more frequent with silastic-band technique. Long-term complications, such as dysmenorrhea and menometrorrhagia and especially those resulting in hysterectomy after laparoscopy, are infrequent. Pregnancy rates are low after laparoscopic sterilization with coagulation and silastic bands as compared to the clip. Rates of complications with sterilization combined with abortion or delivery are only slightly higher than after abortion without sterilization and much less than the combined complications that would be anticipated from abortion and interval sterilization. To make colpotomy, culdoscopy and minilaparotomy easier and potentially safer, mechanical techniques using the spring-loaded clip and silastic band are being evaluated. Simplified techniques that can be administered via the cervix, such as Quinacrine, may be practical in the future.

  3. Is cosmology compatible with sterile neutrinos?

    SciTech Connect

    Dodelson, Scott; Melchiorri, Alessandro; Slosar, Anze; /Ljubljana U.

    2005-11-01

    By combining data from cosmic microwave background (CMB) experiments (including the recent BOOMERANG-2K2 results), large scale structure (LSS) and Lyman-{alpha} forest observations, we constrain the hypothesis of a fourth, sterile, massive neutrino. For the 3 massless + 1 massive neutrino case we bound the mass of the sterile neutrino to m{sub s} < 0.55eV at 95% c.l.. These results exclude at high significance the sterile neutrino hypothesis as an explanation of the LSND anomaly. We then generalize the analysis to account for active neutrino masses (which tightens the limit to m{sub s} < 0.51eV) and the possibility that the sterile abundance is not thermal. In the latter case, the constraints in the (mass, density) plane are non-trivial. For a mass of > 1eV or < 0.05eV the cosmological energy density in sterile neutrinos is always constrained to be {omega}{sub {nu}} < 0.005 at 95% c.l.. However, for a sterile neutrino mass of {approx} 0.25 eV, {omega}{sub {nu}} can be as large as 0.015.

  4. Choosing a low-temperature sterilization technology.

    PubMed

    1999-11-01

    Low-temperature sterilization technologies are used instead of steam for sterilizing heat-sensitive or moisture-intolerant surgical equipment and supplies. In this Guidance Article, we describe several common alternatives, but we focus specifically on the two that have generated the most interest in recent years: ethylene oxide (EtO) and gas plasma sterilization. Ethylene oxide has been used as a low-temperature sterilization technology since the 1950s. Although EtO can be used safely, exposure to this gas is known to be a health hazard, and the emissions from certain EtO sterilizers are known to pollute the atmosphere. For these reasons, the use of EtO is regulated--more strictly in some regions than in others--and many healthcare facilities have decided to investigate alternative technologies. Gas plasma sterilization emerged in the 1990s as one promising alternative. This method appears to pose fewer health and environmental risks, and it offers faster turnaround times. However, this technology also has some limitations. We describe the advantages and disadvantages of both methods, along with the factors to consider when selecting from among these alternatives, in this Guidance Article.

  5. Production of a sterile species: Quantum kinetics

    SciTech Connect

    Ho, Chiu Man; Boyanovsky, D.; Ho, C.M.

    2007-04-23

    Production of a sterile species is studied within an effective model of active-sterile neutrino mixing in a medium in thermal equilibrium. The quantum kinetic equations for the distribution functions and coherences are obtained from two independent methods: the effective action and the quantum master equation. The decoherence time scale for active-sterile oscillations is tau(dec)=2/Gamma(aa), but the evolution of the distribution functions is determined by the two different time scales associated with the damping rates of the quasiparticle modes in the medium: Gamma(1)=Gamma(aa)cos^2theta(m); Gamma(2)=Gamma(aa)sin^2theta(m) where Gamma(aa) is the interaction rate of the active species in the absence of mixing and theta(m) the mixing angle in the medium. These two time scales are widely different away from Mikheyev-Smirnov-Wolfenstein resonances and preclude the kinetic description of active-sterile production in terms of a simple rate equation. We give the complete set of quantum kinetic equations for the active and sterile populations and coherences and discuss in detail the various approximations. A generalization of the active-sterile transition probability in a medium is provided via the quantum master equation. We derive explicitly the usual quantum kinetic equations in terms of the"polarization vector" and show their equivalence to those obtained from the quantum master equation and effective action.

  6. Conference reports

    NASA Astrophysics Data System (ADS)

    Dongpei, Chen; Yulong, Ma

    1994-12-01

    The Ultrasonic Electronics Branch Society of the China Acoustics Society, and the Electronics Countermeasure Branch Society of the China Electronics Society held and All-China Applications Conference of Ultrasonic Electronics Devices in Electronic Countermeasures, Radar and Military Communication Technology. A total of 66 papers was received by the conference with contents relating to surface acoustic wave devices, high-frequency acoustic wave devices, acousto-optical devices, applications of devices in radar, applications of devices in electronic countermeasures, and applications of devices in military communication systems.

  7. Electroporation System for Sterilizing Water

    NASA Technical Reports Server (NTRS)

    Schlager, Kenneth J.

    2005-01-01

    A prototype of an electroporation system for sterilizing wastewater or drinking water has been developed. In electroporation, applied electric fields cause transient and/or permanent changes in the porosities of living cells. Electroporation at lower field strengths can be exploited to increase the efficiency of chemical disinfection (as in chlorination). Electroporation at higher field strengths is capable of inactivating and even killing bacteria and other pathogens, without use of chemicals. Hence, electroporation is at least a partial alternative to chlorination. The transient changes that occur in micro-organisms at lower electric-field strengths include significantly increased uptake of ions and molecules. Such increased uptake makes it possible to achieve disinfection at lower doses of chemicals (e.g., chlorine or ozone) than would otherwise be needed. Lower doses translate to lower costs and reduced concentrations of such carcinogenic chemical byproducts as trichloromethane. Higher electric fields cause cell membranes to lose semipermeability and thereby become unable to function as selective osmotic barriers between the cells and the environment. This loss of function is the cause of the cell death at higher electric-field intensities. Experimental evidence does not indicate cell lysis but, rather, combined leaking of cell proteins out of the cells as well as invasion of foreign chemical compounds into the cells. The concept of electroporation is not new: it has been applied in molecular biology and genetic engineering for decades. However, the laboratory-scale electroporators used heretofore have been built around small (400-microliter) cuvettes, partly because the smallness facilitates the generation of electric fields of sufficient magnitude to cause electroporation. Moreover, most laboratory- scale electroporators have been designed for testing static water. In contrast, the treatment cell in the present system is much larger and features a flow

  8. Using high-temperature formaldehyde sterilization as a model for studying gaseous sterilization.

    PubMed

    Mosley, Gregg A

    2008-01-01

    This study uses the high-temperature formaldehyde sterilization system provided by the Harvey Chemiclave, manufactured by Barnstead Thermolyne Corporation (Dubuque, IA), as a model to investigate certain phenomena associated with gaseous chemical sterilization systems. Although formaldehyde sterilization presents some unique and complex system attributes, the current studies provide helpful insights into general sterilization methods by chemicals in the gaseous state. Both population recovery and fraction negative (FN) techniques were used to assay surviving populations from biological indicators of the organism Geobacillus stearothermophilus following exposure to incremental Chemiclave cycles. Models 5500 and 6000 of the Barnstead/Thermolyne Chemiclave were used in the study. Reusable instruments such as scalers, explorers, and various hinged pieces were tested in minimum versus maximum load studies. Population recovery study results demonstrated that lethality rates increase with time throughout the Chemiclave sterilization process and that there are significant variations in lethality according to load location. The population recovery data in conjunction with the FN studies and temperature data confirm that one-half the full-cycle time is not a good estimator of one-half the full-cycle lethality because lethality curves are concave downward and lethality varies by load location. This conclusion can also be applied to other types of gaseous, chemical sterilization such as ethylene oxide. The work outlined in this study was a result of investigations into the parameters affecting formaldehyde chemical vapor sterilization with the Harvey Chemiclave sterilizer. During these studies, it became apparent that results clearly depicted the effects of continued acceleration of the rate of microbial lethality, as well as variations in delivered lethality as a function of position in the sterilizer load. This publication focuses on these observations because they are

  9. Sterilization techniques for biodegradable scaffolds in tissue engineering applications

    PubMed Central

    Dai, Zheng; Ronholm, Jennifer; Tian, Yiping; Sethi, Benu; Cao, Xudong

    2016-01-01

    Biodegradable scaffolds have been extensively studied due to their wide applications in biomaterials and tissue engineering. However, infections associated with in vivo use of these scaffolds by different microbiological contaminants remain to be a significant challenge. This review focuses on different sterilization techniques including heat, chemical, irradiation, and other novel sterilization techniques for various biodegradable scaffolds. Comparisons of these techniques, including their sterilization mechanisms, post-sterilization effects, and sterilization efficiencies, are discussed. PMID:27247758

  10. Method and apparatus for sterilizing and charging batteries

    SciTech Connect

    Linden, H.A.

    1987-02-03

    An apparatus is described for providing at least one sterile, charged battery for use in a sterile field comprising: a container adapted to permit the entrance of a sterilant and to prevent the entrance of contaminants, the container being adapted to house the battery during sterilization and storage. The container has means of charging the battery therein while maintaining the battery in a sterile state.

  11. Thermal Profile of Metallic Beads in a Bead Sterilizer,

    DTIC Science & Technology

    1986-08-01

    another commonly used chairside sterilization method, principally for endodontic instruments. The bead sterilizer consists of a heated chamber containing...sterilization of endodontic instruments. However, several investigators have shown sterilization times ranging from 3 seconds to 14 minutes, are...et.al. The effect of autoclave sterilization on endodontic files. Oral Surg 55(2): 204-207, 1983. 3. Parkes, R. B. and Kolstad, R. A. Effects of

  12. Conference Summary

    ERIC Educational Resources Information Center

    Doherty, Cait

    2009-01-01

    This article summarizes an original conference, organised by the Child Care Research Forum (http://www.qub.ac.uk/sites/ccrf/), which brought together experts from all over Northern Ireland to showcase some of the wealth of research with children and young people that is going on in the country today. Developed around the six high-level outcomes of…

  13. The conference

    Treesearch

    Gordon M. Heisler; Lee P. Herrington

    1977-01-01

    This is a report on the Conference on Metropolitan Physical Environment, held in August 1975 at Syracuse, N.Y., where some 160 scientists and planners met to discuss the use of vegetation, space, and structures to improve the amenities for people who live in metropolitan areas.

  14. Conference Space

    ERIC Educational Resources Information Center

    Tillett, Wade

    2016-01-01

    The following is an exploration of the spatial configurations (and their implications) within a typical panel session at an academic conference. The presenter initially takes up different roles and hyperbolically describes some possible messages that the spatial arrangement sends. Eventually, the presenter engages the audience members in atypical…

  15. Conference Space

    ERIC Educational Resources Information Center

    Tillett, Wade

    2016-01-01

    The following is an exploration of the spatial configurations (and their implications) within a typical panel session at an academic conference. The presenter initially takes up different roles and hyperbolically describes some possible messages that the spatial arrangement sends. Eventually, the presenter engages the audience members in atypical…

  16. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    PubMed

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  17. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells

    PubMed Central

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M.

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450–463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  18. Anesthesia for outpatient female sterilization.

    PubMed

    Fishburne, J I

    1983-04-01

    This issue of the Bulletin deals with the principles of anesthesia for outpatient female sterilization with emphasis on techniques for laparoscopy and minilaparotomy. General anesthesia techniques provide analgesia, amnesia, and muscle relaxation and are particularly useful for managing the anxious patient. Disadvantages include increased expense, need for specialized equipment, and highly trained personnel, and delayed recovery. Complications, though relatively rare, can be life-threatening and include aspiration of stomach contents, hypoxia, hypercarbia, hypotension, hypertension, cardiac arrhythmias, cardiorespiratory arrest, and death. There is no single preferred technique of general anesthesia, athough most anesthetists employ methods that allow rapid recovery of faculties, enabling the patient to be discharged soon after surgery. To accomplish this end, light anesthesia with sodium thiopental induction and nitrous oxide maintenance is often used. Short duration muscle relaxation with an agent such as succinylcholine supplements this technique. Other techniques include light anesthesia with inhalational anesthetic agents and the use of intravenous ketamine. Local anesthesia augmented by systemic and/or inhalational analgesia is supplanting general anesthesia techniques for laparoscopy in many locales. This approach is also particularly well-suited for minilaparotomy in developing countries, where it has achieved its greatest popularity. The local technique carries with it reduced morbidity and mortality but may not entirely relieve discomfort. The primary danger of local anesthesia is respiratory depression due to excessive narcosis and sedation. The operator must be alert to the action of the drugs and should always use the minimal effective dose. Although toxicity due to overdosage with local anesthetic drugs is occasionally experienced, allergic reactions to the amide-linkage drugs such as lidocaine or bupivacaine are exceedingly rare. For outpatient

  19. Sterilization Performance and Material Compatibility of Sterilizer for Dental Instruments using RF Oxygen Plasma

    NASA Astrophysics Data System (ADS)

    Sakai, Yasuhiro; Liu, Zhen; Hayashi, Nobuya; Goto, Masaaki

    2015-09-01

    The sterilization performance and material compatibility of low-pressure RF plasma sterilization method for dental instruments were investigated. RF electrode used in this experiment has been optimized for sterilization of dental instruments. The vial-type biological indicator (BI) simulating tiny space of dental instrument was used for evaluation of the sterilization performance. The pressure in the stainless chamber was fixed at 60 Pa. Sterilization of BI was achieved in shortest time 40 min at 80 W, and the sterilization effect was confirmed using three BIs. Light emission spectra of oxygen plasma indicated that production of atomic oxygen and excited oxygen molecule are maximum at pressure of 20 Pa and 200 Pa, respectively. Sterilization results of BIs indicated that successful rate increases with the oxygen pressure towards 200 Pa. Therefore, the excited oxygen molecule is deduced to be a major factor of the sterilization of BI. Surface morphology of dental instruments such as diamond bar was evaluated using scanning electron microscope (SEM). The deterioration of fine crystals of diamond bar has not observed after the plasma irradiation for 120 min with RF input power was 60W and pressure was 200 Pa.

  20. Experiences of coercion to sterilize and forced sterilization among women living with HIV in Latin America

    PubMed Central

    Kendall, Tamil; Albert, Claire

    2015-01-01

    Introduction Forced and coerced sterilization is an internationally recognized human rights violation reported by women living with HIV (WLHIV) around the globe. Forced sterilization occurs when a person is sterilized without her knowledge or informed consent. Coerced sterilization occurs when misinformation, intimidation tactics, financial incentives or access to health services or employment are used to compel individuals to accept the procedure. Methods Drawing on community-based research with 285 WLHIV from four Latin American countries (El Salvador, Honduras, Mexico and Nicaragua), we conduct thematic qualitative analysis of reports of how and when healthcare providers pressured women to sterilize and multivariate logistic regression to assess whether social and economic characteristics and fertility history were associated with pressure to sterilize. Results A quarter (23%) of the participant WLHIV experienced pressure to sterilize post-diagnosis. WLHIV who had a pregnancy during which they (and their healthcare providers) knew their HIV diagnosis were almost six times more likely to experience coercive or forced sterilization than WLHIV who did not have a pregnancy with a known diagnosis (OR 5.66 CI 95% 2.35–13.58 p≤0.001). WLHIV reported that healthcare providers told them that living with HIV annulled their right to choose the number and spacing of their children and their contraceptive method, employed misinformation about the consequences of a subsequent pregnancy for women's and children's health, and denied medical services needed to prevent vertical (mother-to-child) HIV transmission to coerce women into accepting sterilization. Forced sterilization was practiced during caesarean delivery. Conclusions The experiences of WLHIV indicate that HIV-related stigma and discrimination by healthcare providers is a primary driver of coercive and forced sterilization. WLHIV are particularly vulnerable when seeking maternal health services. Health worker

  1. Revisiting cosmological bounds on sterile neutrinos

    SciTech Connect

    Vincent, Aaron C.; Martínez, Enrique Fernández; Lattanzi, Massimiliano E-mail: enrique.fernandez-martinez@uam.es E-mail: omena@ific.uv.es

    2015-04-01

    We employ state-of-the art cosmological observables including supernova surveys and BAO information to provide constraints on the mass and mixing angle of a non-resonantly produced sterile neutrino species, showing that cosmology can effectively rule out sterile neutrinos which decay between BBN and the present day. The decoupling of an additional heavy neutrino species can modify the time dependence of the Universe's expansion between BBN and recombination and, in extreme cases, lead to an additional matter-dominated period; while this could naively lead to a younger Universe with a larger Hubble parameter, it could later be compensated by the extra radiation expected in the form of neutrinos from sterile decay. However, recombination-era observables including the Cosmic Microwave Background (CMB), the shift parameter R{sub CMB} and the sound horizon r{sub s} from Baryon Acoustic Oscillations (BAO) severely constrain this scenario. We self-consistently include the full time-evolution of the coupled sterile neutrino and standard model sectors in an MCMC, showing that if decay occurs after BBN, the sterile neutrino is essentially bounded by the constraint sin{sup 2}θ ∼< 0.026 (m{sub s}/eV){sup −2}.

  2. Mercury release during autoclave sterilization of amalgam.

    PubMed

    Parsell, D E; Karns, L; Buchanan, W T; Johnson, R B

    1996-05-01

    Natural teeth are an invaluable teaching tool for preclinical instruction in operative dentistry and endodontic techniques. Cavity preparation in teeth containing amalgam restorations is a realistic simulation of an often experienced clinical situation. As various pathogens are contained in saliva, teeth must be disinfected before use by students. The purpose of this study is to indirectly evaluate whether mercury vapor is released from amalgam restorations in such teeth during steam autoclave sterilization. Mercury vapor detection, sample mass changes and x-ray fluorescence data were collected from experimental steam autoclave sterilization of amalgam samples sealed in autoclave bags. All of the data showed evidence of mercury vapor generation coincident to steam autoclave sterilization. Mercury vapor levels within the room where amalgam was exposed to steam autoclave sterilization reached levels that constitute an unnecessary health risk to dental personnel. The volume of amalgam tested simulated that contained in 175 amalgam restored teeth. Initial venting of the autoclave chamber produced mercury vapor concentrations significantly in excess of OSHA vapor concentration ceiling levels. Thus, the use of a steam autoclave for sterilization of amalgam containing teeth for use in preclinical laboratory exercises may be harmful to personnel involved.

  3. Is cosmology compatible with sterile neutrinos?

    PubMed

    Dodelson, Scott; Melchiorri, Alessandro; Slosar, Anze

    2006-07-28

    By combining data from cosmic microwave background experiments (including the recent WMAP third year results), large scale structure, and Lyman-alpha forest observations, we constrain the hypothesis of a fourth, sterile, massive neutrino. For the 3 massless+1 massive neutrino case, we bound the mass of the sterile neutrino to ms<0.26 eV (0.44 eV) at 95% (99.9%) C.L., which excludes at high significance the sterile neutrino hypothesis as an explanation of the LSND anomaly. We generalize the analysis to account for active neutrino masses and the possibility that the sterile abundance is not thermal. In the latter case, the contraints in the plane are nontrivial. For a mass of >1 or <0.05 eV, the cosmological energy density in sterile neutrinos is always constrained to be omeganu<0.003 at 95% C.L., but for a mass of approximately 0.25 eV, omeganu can be as large as 0.01.

  4. Georgia Supreme Court invalidates involuntary sterilization statute.

    PubMed

    Harper, T D

    1983-11-01

    In the US, the concept of eugenics has been limited to restrictions on the reproductive capabilities of criminals and the mentally defective. Moreover, the rights of persons subject to this restriction have been enhanced by recent judicial recognition of procreation as a fundamental right. Constitutional challenges have been mounted on the grounds that sterilization statutes constitute cruel or unusual punishment, a violation of the Equal Protection clause, an unlawful delegation of legislative or judicial powers, a bill of attainder, or a violation of the right to life, liberty, and the pursuit of happiness. These challenges have resulted in a reduction in the number of state-mandated sterilizations. This paper reviews the Georgia Supreme Court's recent invalidation of a 1970 statute authorizing the sterilization of mentally incompetent persons (O.C.G.A. 31-20-3). Motes v. Hall County Department of Family and Children Services, filed on behalf of a 21-year old retarded woman, challenged the statute as a violation of Motes' constitutional rights to due process and equal protection and contended that the state was required to prove the necessity of sterilization by more than a simple preponderance of the evidence. The Georgia Supreme Court negated both the sterilization order and the statute upon which it was based. In its decision, the Court recognized that an intrusion upon so fundamental a right as the ability to bear children requires proof by the state of at least "clear and convincing evidence" of the necessity of such an act.

  5. Sterilization of instruments in solar ovens.

    PubMed

    Jørgensen, A F; Nøhr, K; Boisen, F; Nøhr, J

    2002-01-01

    The sterilization of instruments in rural health clinics in less developed countries is an increasing problem as chemical methods can no longer be recommended and fuel wood is becoming increasingly scarce. It seems obvious, therefore, to utilize solar energy for sterilization purposes. A solar oven was designed and manufactured using local materials and simple tools. It was tested by physical, chemical and microbiological methods and, after successful testing, installed in a rural clinic. The oven was able to generate temperatures above 180 degrees C. On days with direct sunlight the oven fulfilled the international recommendations for hot air sterilization. The chemical indicators, Browne's tubes type 3 and 5, also changed colour. It was difficult to reach the right value for the sterilization effect during months with a low sun position. A moveable oven, or two ovens, must be installed to solve this problem. The solar oven has proven to be a realistic method for the sterilization of instruments. The solar oven is easy to make and use. It saves fuel and can be used in most tropical areas.

  6. Immediate use steam sterilization: it's all about the process.

    PubMed

    Nania, Paula

    2013-07-01

    Proper reprocessing of surgical instrumentation assists in infection prevention efforts. Immediate use steam sterilization, previously known as flash sterilization, is an effective method of sterilization if it is performed according to manufacturers' validated instructions. Items that undergo immediate use steam sterilization are subject to the same cleaning and decontamination requirements that apply to preparing items for terminal sterilization, and manufacturers' instructions for use must be strictly followed. In 2009, The Joint Commission revised its position statement on flash sterilization and emphasized that three critical steps of reprocessing must be followed to ensure sterility (ie, cleaning and decontamination, sterilization, aseptic transfer) and that complete documentation must be available for each immediate use steam sterilization cycle so that the device is traceable to the patient if problems arise. Copyright © 2013 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  7. Radiation sterilization of tissue allografts: A review

    PubMed Central

    Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

    2016-01-01

    Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts. PMID:27158422

  8. Light sterile neutrinos in the early universe

    SciTech Connect

    Lunardini, Cecilia

    2014-06-24

    Cosmological and terrestrial data suggests the number of light neutrinos may be greater than 3, motivating a careful reexamination of cosmological bounds on extra light species. Big bang nucleosynthesis constrains the number of relativistic neutrino species present during nucleosynthesis, N{sub eff}{sup BBN}, while measurements of the cosmic microwave background (CMB) angular power spectrum constrain the effective energy density in relativistic neutrinos at the time of matter-radiation equality, N{sub eff}{sup CMB}. We review a scenario with two sterile neutrinos and explore whether partial thermalization of the sterile states can ease the tension between cosmological constraints on N{sub eff}{sup BBN} and terrestrial data. We conclude that, still, two additional light sterile neutrinos species cannot fit all the data at the 95% confidence level.

  9. Radiation sterilization of tissue allografts: A review.

    PubMed

    Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

    2016-04-28

    Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts.

  10. Female sterilization by Falope ring ligation.

    PubMed Central

    Lalonde, A. B.

    1982-01-01

    Sterilization with the Falope Ring may be performed by means of laparoscopy of the minilaparotomy. This technique avoids the potential hazards of electrocoagulation, such as intestinal burns. Among the 825 cases reported in this paper there was only one serious complication, an ectopic pregnancy. One other patient had an undetected early pregnancy at the time of sterilization. Two patients became pregnant 4 and 42 month after the procedure. In most cases a diagnostic dilatation and curettage was done before hand. Pathological study of the fallopian tubes of one patient 28 days after the ring was applied revealed complete occlusion of the buckled segment of each tube. Falope Ring sterilization is simple, effective and safe, and the rate of subsequent pregnancy is lower than with conventional burning or clipping techniques. Images FIG. 7 FIG. 8 PMID:7059889

  11. Sterilization and disinfection in the physician's office.

    PubMed Central

    Drummond, D C; Skidmore, A G

    1991-01-01

    OBJECTIVE: To review the principles and practice of sterilization and disinfection of medical instruments in the office setting. DATA SOURCES: Searches of MEDLINE for articles published from 1980 to 1990 on disinfection, sterilization, cross infection, surgical instruments and iatrogenic disease, bibliographies, standard texts and reference material located in a central processing department. STUDY SELECTION: We reviewed surveys of decontamination practices in physicians' offices, reviews of current recommendations for office decontamination procedures, case reports of cross infection in offices and much of the standard reference material on decontamination theory and practice. DATA SYNTHESIS: There have been few surveys of physicians' decontamination practices and few case reports of cross infection. Office practitioners have little access to practical information on sterilization and disinfection. CONCLUSION: The increasing threat of cross infection from medical instruments calls for greater knowledge about decontamination. We have adapted material from various sources and offer a primer on the subject. PMID:1913427

  12. The Propensity of Pentatricopeptide Repeat Genes to Evolve into Restorers of Cytoplasmic Male Sterility

    PubMed Central

    Gaborieau, Lydiane; Brown, Gregory G.; Mireau, Hakim

    2016-01-01

    Cytoplasmic male sterility (CMS) is a widespread phenotype in plants, which present a defect in the production of functional pollen. The male sterilizing factors usually consist of unusual genes or open reading frames encoded by the mitochondrial genome. CMS can be suppressed by specific nuclear genes called restorers of fertility (Rfs). In the majority of cases, Rf genes produce proteins that act directly on the CMS conferring mitochondrial transcripts by binding them specifically and promoting processing events. In this review, we explore the wide array of mechanisms guiding fertility restoration. PPR proteins represent the most frequent protein class among identified Rfs and they exhibit ideal characteristics to evolve into restorer of fertility when the mechanism of restoration implies a post-transcriptional action. Here, we review the literature that highlights those characteristics and help explain why PPR proteins are ideal for the roles they play as restorers of fertility. PMID:27999582

  13. Further characterization of the Odysseus locus of hybrid sterility in Drosophila: one gene is not enough.

    PubMed

    Perez, D E; Wu, C I

    1995-05-01

    Previously we mapped by genetical and molecular means a gene that contributes to hybrid-male sterility between Drosophila mauritiana and D. simulans to the cytological interval of 16D. In this report, we refine the mapping of this gene, Odysseus (Ods) and show that it can be delineated to a region the size of an average gene. We further demonstrate that, while Ods appears to be a discrete element, it requires other nearby gene(s) to be cointrogressed to confer full hybrid sterility effect. This observation is in agreement with the view that reproductive isolation between closely related species of Drosophila is usually caused by several genes of weak effect from the same species that interact strongly among themselves as well as with the foreign genetic background.

  14. About the Sterilization of Chitosan Hydrogel Nanoparticles.

    PubMed

    Galante, Raquel; Rediguieri, Carolina F; Kikuchi, Irene Satiko; Vasquez, Pablo A S; Colaço, Rogério; Serro, Ana Paula; Pinto, Terezinha J A

    2016-01-01

    In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

  15. Biological Sterilization of Returned Mars Samples

    NASA Technical Reports Server (NTRS)

    Allen, C. C.; Albert, F. G.; Combie, J.; Bodnar, R. J.; Hamilton, V. E.; Jolliff, B. L.; Kuebler, K.; Wang, A.; Lindstrom, D. J.; Morris, P. A.

    1999-01-01

    Martian rock and soil, collected by robotic spacecraft, will be returned to terrestrial laboratories early in the next century. Current plans call for the samples to be immediately placed into biological containment and tested for signs of present or past life and biological hazards. It is recommended that "Controlled distribution of unsterilized materials from Mars should occur only if rigorous analyses determine that the materials do not constitute a biological hazard. If any portion of the sample is removed from containment prior to completion of these analyses it should first be sterilized." While sterilization of Mars samples may not be required, an acceptable method must be available before the samples are returned to Earth. The sterilization method should be capable of destroying a wide range of organisms with minimal effects on the geologic samples. A variety of biological sterilization techniques and materials are currently in use, including dry heat, high pressure steam, gases, plasmas and ionizing radiation. Gamma radiation is routinely used to inactivate viruses and destroy bacteria in medical research. Many commercial sterilizers use Co-60 , which emits gamma photons of 1.17 and 1.33 MeV. Absorbed doses of approximately 1 Mrad (10(exp 8) ergs/g) destroy most bacteria. This study investigates the effects of lethal doses of Co-60 gamma radiation on materials similar to those anticipated to be returned from Mars. The goals are to determine the gamma dose required to kill microorganisms in rock and soil samples and to determine the effects of gamma sterilization on the samples' isotopic, chemical and physical properties. Additional information is contained in the original extended abstract.

  16. Biological Sterilization of Returned Mars Samples

    NASA Technical Reports Server (NTRS)

    Allen, C. C.; Albert, F. G.; Combie, J.; Bodnar, R. J.; Hamilton, V. E.; Jolliff, B. L.; Kuebler, K.; Wang, A.; Lindstrom, D. J.; Morris, P. A.

    1999-01-01

    Martian rock and soil, collected by robotic spacecraft, will be returned to terrestrial laboratories early in the next century. Current plans call for the samples to be immediately placed into biological containment and tested for signs of present or past life and biological hazards. It is recommended that "Controlled distribution of unsterilized materials from Mars should occur only if rigorous analyses determine that the materials do not constitute a biological hazard. If any portion of the sample is removed from containment prior to completion of these analyses it should first be sterilized." While sterilization of Mars samples may not be required, an acceptable method must be available before the samples are returned to Earth. The sterilization method should be capable of destroying a wide range of organisms with minimal effects on the geologic samples. A variety of biological sterilization techniques and materials are currently in use, including dry heat, high pressure steam, gases, plasmas and ionizing radiation. Gamma radiation is routinely used to inactivate viruses and destroy bacteria in medical research. Many commercial sterilizers use Co-60 , which emits gamma photons of 1.17 and 1.33 MeV. Absorbed doses of approximately 1 Mrad (10(exp 8) ergs/g) destroy most bacteria. This study investigates the effects of lethal doses of Co-60 gamma radiation on materials similar to those anticipated to be returned from Mars. The goals are to determine the gamma dose required to kill microorganisms in rock and soil samples and to determine the effects of gamma sterilization on the samples' isotopic, chemical and physical properties. Additional information is contained in the original extended abstract.

  17. About the Sterilization of Chitosan Hydrogel Nanoparticles

    PubMed Central

    Galante, Raquel; Rediguieri, Carolina F.; Kikuchi, Irene Satiko; Vasquez, Pablo A. S.; Colaço, Rogério; Pinto, Terezinha J. A.

    2016-01-01

    In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles. PMID:28002493

  18. STERILIZED in the Name of Public Health

    PubMed Central

    Stern, Alexandra Minna

    2005-01-01

    In exploring the history of involuntary sterilization in California, I connect the approximately 20 000 operations performed on patients in state institutions between 1909 and 1979 to the federally funded procedures carried out at a Los Angeles County hospital in the early 1970s. Highlighting the confluence of factors that facilitated widespread sterilization abuse in the early 1970s, I trace prosterilization arguments predicated on the protection of public health. This historical overview raises important questions about the legacy of eugenics in contemporary California and relates the past to recent developments in health care delivery and genetic screening. PMID:15983269

  19. Decontamination formulations for disinfection and sterilization

    DOEpatents

    Tucker, Mark D.; Engler, Daniel E.

    2007-09-18

    Aqueous decontamination formulations that neutralize biological pathogens for disinfection and sterilization applications. Examples of suitable applications include disinfection of food processing equipment, disinfection of areas containing livestock, mold remediation, sterilization of medical instruments and direct disinfection of food surfaces, such as beef carcasses. The formulations include at least one reactive compound, bleaching activator, inorganic base, and water. The formulations can be packaged as a two-part kit system, and can have a pH value in the range of 7-8.

  20. [Treatment of anovulatory cycle induced sterility].

    PubMed

    Botella Llusia, J

    1983-03-01

    Of all the clinical aspects of human sterility, the anovulatory cycle is undoubtedly 1 that has produced the widest range of therapuetic successes. While in other fields progress has been very slow (male sterility or tubal obstruction), ovarian pharmacoendocrinology has shown several advances over recent years. This progress is due partly to new chemicals such as urinary menopausal gonadotropins, LH-RH, and their analogues Clomiphene and Bromocriptine. Contributing further to these good results is a greater knowledge of the etiology of anovulation and a more accurate selection of cases for treatment.

  1. Sterile infiltrates after cross-linking.

    PubMed

    García de Oteyza, G; Álvarez de Toledo, J

    2017-09-01

    A 20 year-old woman presented with an asymmetric bilateral keratoconus. Cross-linking of the right eye was performed due of its topographic and pachymetric conditions. Three days after the procedure, the patient presented with some corneal infiltrates that where classified as sterile. Cross-linking is known for its efficacy and safety. Nevertheless, there can be complications. Sterile infiltrates have already been described, although their aetiology is still not clear. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Microbiological Aspects of Ethylene Oxide Sterilization

    PubMed Central

    Kereluk, K.; Gammon, R. A.; Lloyd, R. S.

    1970-01-01

    A specially built thermochemical death-rate apparatus is described which can be used to determine the resistance of microorganisms to ethylene oxide under controlled conditions. The apparatus was designed to provide instantaneous exposure of microorganisms to ethylene oxide and to eliminate variables that could result in errors when death kinetic reaction rates are calculated. The apparatus is used to obtain ethylene oxide resistance data which are useful in evaluating and developing sterilizing cycles for materials with known bacterial concentrations, as well as for calculating probability factors on which a given test condition can be expected to provide sterilization. PMID:4984364

  3. Solar neutrino detectors as sterile neutrino hunters

    NASA Astrophysics Data System (ADS)

    Pallavicini, Marco; Borexino-SOX Collaboration; Agostini, M.; Altenmüller, K.; Appel, S.; Atroshchenko, V.; Bellini, G.; Benziger, J.; Berton, N.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Carlini, M.; Cavalcante, P.; Chepurnov, A.; Choi, K.; Cloué, O.; Cribier, M.; D’Angelo, D.; Davini, S.; Derbin, A.; Di Noto, L.; Drachnev, I.; Durero, M.; Etenko, A.; Farinon, S.; Fischer, V.; Fomenko, K.; Franco, D.; Gabriele, F.; Gaffiot, J.; Galbiati, C.; Gschwender, M.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Houdy, Th.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jany, A.; Jedrzejczak, K.; Jeschke, D.; Jonquères, N.; Kobychev, V.; Korablev, D.; Korga, G.; Kornoukhov, V.; Kryn, D.; Lachenmaier, T.; Lasserre, T.; Laubenstein, M.; Lehnert, B.; Link, J.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Maricic, J.; Mention, G.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Musenich, R.; Neumair, B.; Oberauer, L.; Ortica, F.; Papp, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Reinert, Y.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Scola, L.; Semenov, D.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Unzhakov, E.; Veyssière, C.; Vishneva, A.; Vivier, M.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Winter, J.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

    2017-09-01

    The large size and the very low radioactive background of solar neutrino detectors such as Borexino at the Gran Sasso Laboratory in Italy offer a unique opportunity to probe the existence of neutrino oscillations into new sterile components by means of carefully designed and well calibrated anti-neutrino and neutrino artificial sources. In this paper we briefly summarise the key elements of the SOX experiment, a program for the search of sterile neutrinos (and other short distance effects) by means of a 144Ce-144Pr anti-neutrino source and, possibly in the medium term future, with a 51Cr neutrino source.

  4. Nursing concerns and hospital product sterilization.

    PubMed

    Rock, R B; Anderson, N A

    1981-01-01

    Nurses and other health care professionals must be aware of the rationale and methodology for in-hospital health care product standardization, including consideration of the hospital standardization committee composition, pilot-study prerequisites, and general evaluation criteria. They must be familiar with the techniques of product sterilization, their effectiveness, and the materials required to maintain sterile product shelf-life until a product is used. Hospital standardization committees can assist in the product-use decisionmaking process. Product evaluation criteria should include considerations pertaining to cost, quality, service, and comparison to similar products.

  5. Modeling the suppression of sea lamprey populations by the release of sterile males or sterile females

    USGS Publications Warehouse

    Klassen, Waldemar; Adams, Jean V.; Twohey, Michael B.

    2004-01-01

    The suppressive effects of trapping adult sea lampreys, Petromyzon marinus Linnaeus, and releasing sterile males (SMRT) or females (SFRT) into a closed system were expressed in deterministic models. Suppression was modeled as a function of the proportion of the population removed by trapping, the number of sterile animals released, the reproductive rate and sex ratio of the population, and (for the SFRT) the rate of polygyny. Releasing sterile males reduced populations more quickly than did the release of sterile females. For a population in which 30% are trapped, sterile animals are initially released at ratio of 10 sterile to 1 fertile animal, 5 adult progeny are produced per fertile mating, 60% are male, and males mate with an average of 1.65 females, the initial population is reduced 87% by SMRT and 68% by SFRT in one generation. The extent of suppression achieved is most sensitive to changes in the initial sterile release ratio. Given the current status of sea lamprey populations and trapping operations in the Great Lakes, the sterile-male-release technique has the best chance for success on a lake-wide basis if implemented in Lake Michigan. The effectiveness of the sterile-female-release technique should be investigated in a controlled study. Advancing trapping technology should be a high priority in the near term, and artificial rearing of sea lampreys to the adult stage should be a high priority in the long term. The diligent pursuit of sea lamprey suppression over a period of several decades can be expected to yield great benefits.

  6. Next conference

    NASA Astrophysics Data System (ADS)

    Hexemer, Alexander; Toney, Michael F.

    2010-11-01

    After the successful conference on Synchrotron Radiation in Polymer Science (SRPS) in Rolduc Abbey (the Netherlands), we are now looking forward to the next meeting in this topical series started in 1995 by H G Zachmann, one of the pioneers of the use of synchrotron radiation techniques in polymer science. Earlier meetings were held in Hamburg (1995), Sheffield (2002), Kyoto (2006), and Rolduc (2009). In September of 2012 the Synchrotron Radiation and Polymer Science V conferences will be organized in a joint effort by the SLAC National Accelerator Laboratory and Lawrence Berkeley National Laboratory. Stanford Linear Accelerator Laboratory Stanford Linear Accelerator Laboratory Advanced Light Source at LBL Advanced Light Source at LBL The conference will be organised in the heart of beautiful San Francisco. The program will consist of invited and contributed lectures divided in sessions on the use of synchrotron SAXS/WAXD, imaging and tomography, soft x-rays, x-ray spectroscopy, GISAXS and reflectivity, micro-beams and hyphenated techniques in polymer science. Poster contributions are more than welcome and will be highlighted during the poster sessions. Visits to both SLAC as well as LBL will be organised. San Francisco can easily be reached. It is served by two major international airports San Francisco International Airport and Oakland International Airport. Both are being served by most major airlines with easy connections to Europe and Asia as well as national destinations. Both also boast excellent connections to San Francisco city centre. We are looking forward to seeing you in the vibrant city by the Bay in September 2012. Golden gate bridge Alexander Hexemer Lawrence Berkeley National Laboratory, Advanced Light Source, Berkeley, CA 94720, USA Michael F Toney Stanford Synchrotron Radiation Lightsource, Menlo Pk, CA 94025, USA E-mail: ahexemer@lbl.gov, mftoney@slac.stanford.edu

  7. The effect of the radio-protective agents ethanol, trimethylglycine, and beer on survival of X-ray-sterilized male Aedes aegypti

    PubMed Central

    2013-01-01

    Background Sterile Insect Technique (SIT) has been successfully implemented to control, and in some cases, eradicate, dipteran insect populations. SIT has great potential as a mosquito control method. Different sterilization methods have been used on mosquitoes ranging from chemosterilization to genetically modified sterile male mosquito strains; however, sterilization with ionizing radiation is the method of choice for effective sterilization of male insects for most species. The lack of gentle radiation methods has resulted in significant complications when SIT has been applied to mosquitoes. Several studies report that irradiating mosquitoes resulted in a decrease in longevity and mating success compared to unirradiated males. The present study explored new protocols for mosquito sterilization with ionizing radiation that minimized detrimental effects on the longevity of irradiated males. Methods We tested three compounds that have been shown to act as radioprotectors in the mouse model system - ethanol, trimethylglycine, and beer. Male Aedes aegypti were treated with one of three chosen potential radioprotectors and were subsequently irradiated with identical doses of long-wavelength X-rays. We evaluated the effect of these radioprotectors on the longevity of male mosquito after irradiation. Results We found that X-ray irradiation with an absorbed dose of 1.17 gy confers complete sterility. Irradiation with this dose significantly shortened the lifespan of male mosquitoes and all three radioprotectors tested significantly enhanced the lifespan of irradiated mosquito males. Conclusion Our results suggest that treatment with ethanol, beer, or trimethylglycine before irradiation can be used to enhance longevity in mosquitoes. PMID:23866939

  8. Conferences revisited

    NASA Astrophysics Data System (ADS)

    Radcliffe, Jonathan

    2008-08-01

    Way back in the mid-1990s, as a young PhD student, I wrote a Lateral Thoughts article about my first experience of an academic conference (Physics World 1994 October p80). It was a peach of a trip - most of the lab decamped to Grenoble for a week of great weather, beautiful scenery and, of course, the physics. A whole new community was there for me to see in action, and the internationality of it all helped us to forget about England's non-appearance in the 1994 World Cup finals.

  9. The role of packaging size on contamination rates during simulated presentation to a sterile field.

    PubMed

    Trier, Tony; Bello, Nora; Bush, Tamara Reid; Bix, Laura

    2014-01-01

    The objective of this study was to assess the impact of package size on the contact between medical devices and non-sterile surfaces (i.e. the hands of the practitioner and the outside of the package) during aseptic presentation to a simulated sterile field. Rationale for this objective stems from the decades-long problem of hospital-acquired infections. This work approaches the problem from a unique perspective, namely packaging size. Randomized complete block design with subsampling. Research study conducted at professional conferences for surgical technologists and nursing professionals. Ninety-seven healthcare providers, primarily surgical technologists and nurses. Participants were gloved and asked to present the contents of six pouches of three different sizes to a simulated sterile field. The exterior of pouches and gloves of participants were coated with a simulated contaminant prior to each opening trial. After presentation to the simulated sterile field, the presence of the contaminant on package contents was recorded as indicative of contact with non-sterile surfaces and analyzed in a binary fashion using a generalized linear mixed model. Recruited subjects were 26-64 years of age (81 females, 16 males), with 2.5-44 years of professional experience. Results indicated a significant main effect of pouch size on contact rate of package contents (P = 0.0108), whereby larger pouches induced greater rates of contact than smaller pouches (estimates±SEM: 14.7±2.9% vs. 6.0±1.7%, respectively). This study utilized novel methodologies which simulate contamination in aseptic presentation. Results of this work indicate that increased contamination rates are associated with larger pouches when compared to smaller pouches. The results add to a growing body of research which investigate packaging's role in serving as a pathway for product contamination during aseptic presentation. Future work should investigate other packaging design factors (e.g. material

  10. Effects of Sterilizing Agents on Microorganisms

    DTIC Science & Technology

    1963-03-01

    vided either is valid at high temperatures. (4) Radiation La Bree, T. R., Fields, M. L., Desrosier, N. W. sterilization may become useful in the beverage ...e’sters, nisin , (’thhvln oxide, diepoxvbutane, (ight chemical formulations upon microbial numbers in hydrogen peroxide, formaldehyde

  11. Male sterility and hybrid seed production

    USDA-ARS?s Scientific Manuscript database

    Sexual reproduction in angiosperms is a complex process that includes a portion of the vegetative generation and all of the sexual generation. Coordination of both female and male reproduction ontogenies must occur. An abnormality anywhere in this process may lead to sterility. Genetic (nuclear) and...

  12. 21 CFR 610.12 - Sterility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) The sterility test must be appropriate to the material being tested such that the material does not... inhibitors, neutralizers, and preservatives, if present, in the tested material; (5) For a culture-based test method, the volume of test material that results in a dilution of the product that is not...

  13. 21 CFR 610.12 - Sterility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) The sterility test must be appropriate to the material being tested such that the material does not... inhibitors, neutralizers, and preservatives, if present, in the tested material; (5) For a culture-based test method, the volume of test material that results in a dilution of the product that is not...

  14. Molecular analysis of cytoplasmic male sterility

    SciTech Connect

    Hanson, M.R.

    1990-01-01

    The ultimate aims of the project are to understand the molecular mechanism of the disruption in pollen development which occurs in cytoplasmic male sterile plants and to understand the control of respiratory energy flow in the higher plant cell. A mitochondrial locus termed S-pcf segregates with sterility and with an alteration in respiration in Petunia. This cloned locus contains three genes, an abnormal fused gene termed pcf, a gene for a subunit of an NADH dehydrogenase complex, and a small ribosomal subunit protein. The pcf gene is comprised of partial sequences of ATPase subunit 9, cytochrome oxidase subunit II, and an unidentified reading frame. Components of the S-Pcf locus will be introduced into the nuclear of a fertile genotype under the control of appropriate regulatory signals, and polypeptide products of introduced genes will be directed to the mitochondrion with a transit peptide. By examining transgenic plants, we can determine what elements of the locus are critical for altered respiration or sterility. Such knowledge could explain how mitochondrial DNA affects pollen development in the large number of plant species which exhibit the agronomically important trait of male sterility. 10 refs., 3 figs.

  15. Advances in Sterilization and Decontamination: a Survey

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Recent technical advances made in the field of sterilization and decontamination and their applicability to private and commercial interests are discussed. Government-sponsored programs by NASA produced the bulk of material presented in this survey. The summary of past and current research discussed is detailed to enhance an effective transfer of technology from NASA to potential users.

  16. The Decision for Male versus Female Sterilization.

    ERIC Educational Resources Information Center

    Clark, Margaret Pruitt; And Others

    1979-01-01

    The increasing popularity of sterilization underscores the need for knowledge about couples choosing male and female procedures. This research delineates four sets of variables that may be important for the decision and examines their relationship with the choice of male or female procedure among a sample of married couples. (Author)

  17. Heat sterilization times of five hardwood species

    Treesearch

    William T. Simpson; Xiping Wang; John W. Forsman; John R. Erickson

    2005-01-01

    Heat sterilization of lumber, timbers, and pallets is currently used to kill insects, thus preventing their transfer between countries in international trade. An important factor in this treatment is the time required for the center of any wood configuration to reach the temperature necessary to kill the insect. This study explored the effect of size (1-, 1.5-, and 2.0...

  18. New technology for sterilization and disinfection.

    PubMed

    Nyström, B

    1991-09-16

    Sterilization with low temperature steam and formaldehyde is a well-known process in many European countries, but little known in the United States. It sterilizes reliably and reproducibly at temperatures greater than or equal to 65 degrees C. With a well-designed cycle, it leaves residues of formaldehyde on sterilized items below 5 micrograms/cm2, measured on a standard filter paper. Formaldehyde levels in air near the autoclave are well below official exposure limits, if at all measurable. Occurrence of late growers in bioindicators, and penetration of the sterilizing media into long narrow lumina, should be validated for new processes. Automated cleaning and disinfection in closed washer-disinfectors and flushing disinfectors are likewise processes relatively little known in the United States. Disinfection is achieved by a final rinse with hot water or steam. Washer-disinfectors are used for surgical instruments, nondisposable anesthesia and other equipment, flushing disinfectors for nondisposable bedpans, wash-bowls, urinals, and similar equipment. They clean well, washer-disinfectors excellently so, and disinfect reliably. With the use of such equipment in wards, surgical departments, and other areas, reliance on chemical germicides can be dramatically reduced and disposables can be replaced by disinfectable nondisposables.

  19. 21 CFR 610.12 - Sterility.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... sterility test of the product. Fluid Thioglycollate Medium shall be stored in the dark at room temperature... for Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood Cells, Anti-Human Globulin, or Blood Grouping Reagent. (ii) Where a...

  20. 21 CFR 610.12 - Sterility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... sterility test of the product. Fluid Thioglycollate Medium shall be stored in the dark at room temperature... for Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood Cells, Anti-Human Globulin, or Blood Grouping Reagent. (ii) Where a...

  1. Sterile Neutrino Experiments I: Accelerator-based

    NASA Astrophysics Data System (ADS)

    Toups, Matthew

    2017-01-01

    The Standard Model is the theory that describes the fundamental constituents of matter and their interactions. Despite its great success, there still exists evidence for a wide range of phenomena, which lie outside the framework of the Standard Model. Among these, neutrino flavor oscillations hold great promise to bring insight to the field towards a theory that transcends the Standard Model. The discovery of light, sterile neutrinos that mix with the three active neutrino flavors and modify the standard three-neutrino oscillation probabilities in vacuum and matter would be a major breakthrough for the field and contribute to our overall understanding of neutrino mass and mixing. Current indications for light sterile neutrinos come from a variety of experiments reporting anomalies. The accelerator-based LSND and MiniBooNE experiments, for example, reported an excess of electron-type neutrinos over short baselines, which if interpreted as due to νμ ->νe (or νμ ->νe) oscillations, would imply the existence of a fourth light neutrino mass state. On the other hand, null results from other accelerator-based neutrino oscillation experiments searching for sterile neutrinos have put constraints on the possible existence of these particles. This talk will review the accelerator-based searches for light, sterile neutrinos as well as the prospects for confirming or refuting their existence in the coming years.

  2. Surface sterilization of hybrid poplar cuttings

    Treesearch

    Alma M. Waterman

    1954-01-01

    Fungus diseases of hybrid poplars may be spread by spores that lodge in the resinous coating of buds of dormant cuttings, and in the lenticels. Surface sterilization by dipping the cuttings in fungicides was tested to determine whether such treatment would prevent the germination of spores of the canker-producing fungi Septoria musiva and Dothichiza populea and the...

  3. [Laparoscopic sterilization using tubal rings and clips].

    PubMed

    Borko, E; Breznik, R; Ivanisević, V; Herzmansky, M

    1980-01-01

    From 1978 to April 1980, 36 laparoscopic sterilization procedures were completed at the Gynecological Department in Maribor. For tubal occlusion in 16 cases Tupla clips and in 20 cases the Tubal Falope ring were used. It appears that the incidence of complications and other technical difficulties is somewhat more frequent with clips. There have been no pregnancies in all these cases.

  4. [Anesthesia for laparoscopy in sterile patients].

    PubMed

    Schönrath, B; Borgwardt, D; Langanke, D; Alexander, H; Baier, D; Haake, K W

    1990-01-01

    During 5 years 382 laparoscopies were carried through in female patients with sterility in different kinds of anaesthesia (Intubation anaesthesia, spinal anaesthesia, and i.v. anaesthesia). We found the most advantageous results in the cases of i.v. anaesthesia with Ketamin and Diazepam.

  5. Perspectives: Eugenics and Sterilization in the Heartland.

    ERIC Educational Resources Information Center

    Wehmeyer, Michael L.

    2003-01-01

    Noting the Governor of Virginia's recent apology for his state's participation in eugenics, this article reviews the history of the sterilization of people with epilepsy and mental retardation in several states, and the importance of the Buck v. Bell (1927) Supreme Court decision in the promotion of eugenics. (Contains references.) (CR)

  6. Compulsory sterilization. (Letter to the editor).

    PubMed

    Nixon, R K

    1972-10-16

    Angela R. Holder's conclusion (221: 229, 1972) that a decline in forced sterilization cases exists because "any system of compulsory sterilization is too near naziism to be acceptable in a democratic society" ignores present realities. At no time in American history has there been greater acceptance of the idea that human procreation must be regulated by coercive means. Many leaders of the movement for population control, for example, openly advocate mandatory sterilization, abortion, and birth control as part of their crash program for population stabilization. Simultaneously, a growing number of those concerned with genetic "quality" demand that individual rights be subordinated or destroyed for the good of society and the species. Meanwhile, the increasing minimization of the enormous complexities of the abortion issue to a morally and medically neutral therapeutic procedure, threatens to make abortions, as well as sterilization, innocu ous public health measures that could be forced on society if circumstan ces dictate. Moreover, as the public is conditioned to believe that these measures lack ethical ramifications, the day is hastened when they can be imposed without significant opposition. full text

  7. Steam sterilization of air turbine dental handpieces.

    PubMed

    Edwardsson, S; Svensäter, G; Birkhed, D

    1983-12-01

    The efficacy of autoclaving high-speed dental handpieces was tested in two types of downward displacement steam sterilizers (instrument autoclaves), commonly used in the dentist's office. Eight series of experiments were performed with various sterilization schedules. Lubrication oils with or without antimicrobial agent were used in four of the series. Each handpiece was inoculated with 1 ml of a suspension containing equal amounts of saliva and spores of Bacillus stearothermophilus (approx. 10(6) spores/ml). Neither sterilization at 120-124 degrees C for 20 min nor at 134-136 degrees C for 10 min resulted in complete inactivation of the spores in series in which the instruments were tested without oil or with oil containing no antimicrobial agent. However, when the handpieces were lubricated with oil containing isopropanol and formaldehyde and the schedule 134-136 degrees C/10 min was used, no growth was observed. The results indicate that instrument autoclaves with built-in programs of 120-124 degrees C/20 min and 134-136 degrees C/10 min could have insufficient capacity to sterilize lubricated or unlubricated dental handpieces. The use of oils containing an antimicrobial agent can overcome this problem.

  8. Sterilization of Microorganisms by Ozone and Ultrasound

    NASA Astrophysics Data System (ADS)

    Krasnyj, V. V.; Klosovskij, A. V.; Panasko, T. A.; Shvets, O. M.; Semenova, O. T.; Taran, V. S.; Tereshin, V. I.

    2008-03-01

    The results of recent experimental methods of sterilization of microorganisms with the use of ozone and ultrasound are presented. The main aim was to optimize the process of sterilization in water solution taking into account the ozone concentration, the power of ultrasonic emitter and the temperature of water. In the present work, the ultrasonic cavitation with simultaneous ozone generation has been used. The high ozone concentration in water solution was achieved by two-barrier glow discharge generated at atmospheric pressure and a cooling thermo-electric module. Such a sterilizer consists of ozone generator in a shape of flat electrodes covered with dielectric material and a high-voltage pulsed power supply of 250 W. The sterilization camera was equipped with ultrasonic source operated at 100 W. The experiments on the inactivation of bacteria of the Bacillus Cereus type were carried out in the distilled water saturated by ozone. The ozone concentration in the aqueous solution was 10 mg/1, whereas the ozone concentration at the output of ozone generator was 30 mg/1. The complete inactivation of spores took 15 min. Selection of the temperature of water, the ozone concentrations and ultrasonic power allowed to determine the time necessary for destroying the row of microorganisms.

  9. Perspectives: Eugenics and Sterilization in the Heartland.

    ERIC Educational Resources Information Center

    Wehmeyer, Michael L.

    2003-01-01

    Noting the Governor of Virginia's recent apology for his state's participation in eugenics, this article reviews the history of the sterilization of people with epilepsy and mental retardation in several states, and the importance of the Buck v. Bell (1927) Supreme Court decision in the promotion of eugenics. (Contains references.) (CR)

  10. Sterile soil from Antarctica: organic analysis.

    PubMed

    Horowitz, N H; Bauman, A J; Cameron, R E; Geiger, P J; Hubbard, J S; Shulman, G P; Simmonds, P G; Westberg, K

    1969-05-30

    Soils from the dry-valley region of Antarctica can be sterile by the usual microbiological criteria and yet contain significant amounts of organic carbon. Examination of one such soil shows that the organic material is finely divided anthracite coal. These findings have significant implications for the biological exploration of Mars.

  11. Light sterile neutrinos after BICEP-2

    SciTech Connect

    Archidiacono, Maria; Hannestad, Steen; Fornengo, Nicolao; Gariazzo, Stefano; Giunti, Carlo; Laveder, Marco E-mail: fornengo@to.infn.it E-mail: giunti@to.infn.it E-mail: marco.laveder@pd.infn.it

    2014-06-01

    The recent discovery of B-modes in the polarization pattern of the Cosmic Microwave Background by the BICEP2 experiment has important implications for neutrino physics. We revisit cosmological bounds on light sterile neutrinos and show that they are compatible with all current cosmological data provided that the mass is relatively low. Using CMB data, including BICEP-2, we find an upper bound of m{sub s} < 0.85 eV (2σ Confidence Level). This bound is strengthened to 0.48 eV when HST measurements of H{sub 0} are included. However, the inclusion of SZ cluster data from the Planck mission and weak gravitational measurements from the CFHTLenS project favours a non-zero sterile neutrino mass of 0.44{sup +0.11}{sub −0.16} eV. Short baseline neutrino oscillations, on the other hand, indicate a new mass state around 1.2 eV. This mass is highly incompatible with cosmological data if the sterile neutrino is fully thermalised (Δχ{sup 2} > 10). However, if the sterile neutrino only partly thermalises it can be compatible with all current data, both cosmological and terrestrial.

  12. SPAN C - Terminal sterilization process analysis program

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Computer program, SPAN-C, measures the dry heat thermal sterilization process applied to a planetary capsule and calculates the time required for heat application, steady state conditions, and cooling. The program is based on the logarithmic survival of micro-organisms. Temperature profiles must be input on cards.

  13. SPAN - Terminal sterilization process analysis program

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Computer program, SPAN, measures the dry heat thermal sterilization process applied to a planetary capsule and calculates the time required for heat application, steady state conditions, and cooling. The program is based on the logarithmic survival of micro-organisms. Temperature profiles must be input on tape.

  14. System for sterilizing objects. [cleaning space vehicle systems

    NASA Technical Reports Server (NTRS)

    Bryan, C. J.; Wright, E. E., Jr.; Moyers, C. V. (Inventor)

    1981-01-01

    A system for producing a stream of humidified sterilizing gas for sterilizing objects such as the water systems of space vehicles and the like includes a source of sterilant gas which is fed to a mixing chamber which has inlet and outlet ports. The level of the water only partially fills the mixing chamber so as to provide an empty space adjacent the top of the chamber. A heater is provided for heating the water in the chamber so as to produce a humidified atmosphere. The sterilant gas is fed through an arcuate shaped tubular member connected to the inlet port of the mixing chamber for producing a vortex type of flow of sterilant gas into the chamber for humidification. A tubular member extends from the mixing chamber for supplying the humidified sterilant gas to the object for being sterilized. Scrubbers are provided for removing the sterilant gas after use.

  15. Red oak borers become sterile when reared under continuous light

    Treesearch

    Jimmy R. Galford

    1975-01-01

    Red oak borers, Enaphalodes rufulus (Haldeman), reared under continuous light for 12 weeks became sterile. Sterility is thought to have been caused by light destroying vitamins essential for fertility

  16. Validation of a microwave sterilizer for injection ampules.

    PubMed

    Sasaki, K; Honda, W; Ohsawa, S; Miyake, Y; Kawashima, Y

    1999-01-01

    A program for validating the microwave sterilizer, which is a new type of sterilizer, was established and implemented. This program includes the following tests specific to microwave sterilizers: the internal pressure strength of ampules, the acceptable range of sterilizing temperature, performance and calibration of the infrared thermometer and the plane blackbody, maintaining of sterilizing temperature, the processing speed (sterilizing time), the unacceptable ampules selection mechanism, microwave leaks, and a microbiological challenge test of the ampule head space using a biological indicator. Injectable preparations of mecobalamin and diprophylline were used as models for validation of the microwave sterilizer. The bioburden approach was used for injectable mecobalamin preparation, and the over-kill approach was used for injectable diprophylline preparation. The basis for practical use of this microwave sterilizer has been confirmed by the establishment and implementation of this validation program.

  17. Selection of biological indicator for validating microwave heating sterilization.

    PubMed

    Sasaki, K; Mori, Y; Honda, W; Miyake, Y

    1998-01-01

    For the purpose of selecting an appropriate biological indicator for evaluation of the effects of microwave heating sterilization, we examined aerobic bacterial spores to determine whether microwaves have non-thermal sterilization effects. After microwave irradiation on dry bacterial spores (three species), none of the bacterial spores were killed. The survival rate of the spores after microwave irradiation of spore suspensions (twelve species) was compared with that after heating by a conventional method. The order of heat resistance in the bacterial species was similar between the two heating methods. Bacillus stearothermophilus spores were the most heat-resistant. These results suggest that microwaves have no non-thermal sterilization effects on bacterial spores, the specific resistant spores to microwave heating, and microwave heating sterilization can be evaluated in the same way as for conventional heating sterilization. As a biological indicator for evaluation of overkill sterilization, B. stearothermophilus spores may be appropriate for microwave heating sterilization as well as steam sterilization.

  18. Sterilization Efficiency of Spore forming Bacteria in Powdery Food by Atmospheric Pressure Plasmas Sterilizer

    NASA Astrophysics Data System (ADS)

    Nagata, Masayoshi; Tanaka, Masashi; Kikuchi, Yusuke

    2015-09-01

    To provide food sterilization method capable of killing highly heat resistant spore forming bacteria, we have studied effects of plasma treatment method at atmospheric pressure in order to develop a new high speed plasma sterilization apparatus with a low cost and a high efficiency. It is also difficult even for the plasma treatment to sterilize powdery food including spices such as soybean, basil and turmeric. This paper describes that an introduction of mechanical rotation of a treatment space increases the efficiency so that perfect inactivation of spore forming bacteria in these materials by a short treatment time has been demonstrated in our experiments. We also will discuss the sterilization mechanism by dielectric barrier discharge.

  19. Device and Container for Reheating and Sterilization

    NASA Technical Reports Server (NTRS)

    Sastry, Sudhir K.; Heskitt, Brian F.; Jun, Soojin; Marcy, Joseph E.; Mahna, Ritesh

    2012-01-01

    Long-duration space missions require the development of improved foods and novel packages that do not represent a significant disposal issue. In addition, it would also be desirable if rapid heating technologies could be used on Earth as well, to improve food quality during a sterilization process. For this purpose, a package equipped with electrodes was developed that will enable rapid reheating of contents via ohmic heating to serving temperature during space vehicle transit. Further, the package is designed with a resealing feature, which enables the package, once used, to contain and sterilize waste, including human waste for storage prior to jettison during a long-duration mission. Ohmic heating is a technology that has been investigated on and off for over a century. Literature indicates that foods processed by ohmic heating are of superior quality to their conventionally processed counterparts. This is due to the speed and uniformity of ohmic heating, which minimizes exposure of sensitive materials to high temperatures. In principle, the material may be heated rapidly to sterilization conditions, cooled rapidly, and stored. The ohmic heating device herein is incorporated within a package. While this by itself is not novel, a reusable feature also was developed with the intent that waste may be stored and re-sterilized within the packages. These would then serve a useful function after their use in food processing and storage. The enclosure should be designed to minimize mass (and for NASA's purposes, Equivalent System Mass, or ESM), while enabling the sterilization function. It should also be electrically insulating. For this reason, Ultem high-strength, machinable electrical insulator was used.

  20. Orthodontic instrument sterilization with microwave irradiation

    PubMed Central

    Yezdani, Arif; Mahalakshmi, Krishnan; Padmavathy, Kesavaram

    2015-01-01

    Objective: This study was designed to evaluate the efficiency of microwave sterilization of orthodontic instruments and molar bands immersed in plain distilled water with and without oral rinse, and to ascertain the minimum time of exposure required to sterilize. Materials and Methods: The orthodontic instruments (hinged and nonhinged), molar bands and mouth mirrorsused in the patient 's mouth were selected for the study. The instruments were divided into two groups – Group I with oral rinse-set A (0.01% chlorhexidine gluconate) and set B (0.025% betadine) and Group II (included sets C and D without oral rinse). The instruments of set A, B and C were microwaved at 2,450 MHz, 800 W for 5 min, whereas, set D was microwaved for 10 min at the same above mentioned specifications. The efficacy of sterilization was assessed by stab inoculation of the instruments onto trypticase soya agar plates. The plates were checked for bacterial growth following incubation at 37 °C for 24 h. For sterility control,Geobacillus stearothermophilus (MTCC 1518) was included. Results: No growth was observed in the plates that were inoculated with the microwaved orthodontic instruments of sets A, B and D, whereas scanty bacterial growth was observed in the plates inoculatedwith the microwaved set C instruments. Conclusion: Effective sterilization was achieved when the orthodontic instruments and molar bands were immersed in distilled water without oral rinse and microwaved for 10 min as also for those that were immersed in distilled water with oral rinse and microwaved for 5 min. PMID:26015686

  1. 42 CFR 441.255 - Sterilization by hysterectomy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Sterilization by hysterectomy. 441.255 Section 441... Sterilizations § 441.255 Sterilization by hysterectomy. (a) FFP is not available in expenditures for a hysterectomy if— (1) It was performed solely for the purpose of rendering an individual permanently incapable...

  2. 42 CFR 441.255 - Sterilization by hysterectomy.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Sterilization by hysterectomy. 441.255 Section 441... Sterilizations § 441.255 Sterilization by hysterectomy. (a) FFP is not available in expenditures for a hysterectomy if— (1) It was performed solely for the purpose of rendering an individual permanently incapable...

  3. 42 CFR 441.255 - Sterilization by hysterectomy.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Sterilization by hysterectomy. 441.255 Section 441... Sterilizations § 441.255 Sterilization by hysterectomy. (a) FFP is not available in expenditures for a hysterectomy if— (1) It was performed solely for the purpose of rendering an individual permanently incapable...

  4. 42 CFR 441.255 - Sterilization by hysterectomy.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Sterilization by hysterectomy. 441.255 Section 441... Sterilizations § 441.255 Sterilization by hysterectomy. (a) FFP is not available in expenditures for a hysterectomy if— (1) It was performed solely for the purpose of rendering an individual permanently incapable...

  5. 42 CFR 441.255 - Sterilization by hysterectomy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Sterilization by hysterectomy. 441.255 Section 441... Sterilizations § 441.255 Sterilization by hysterectomy. (a) FFP is not available in expenditures for a hysterectomy if— (1) It was performed solely for the purpose of rendering an individual permanently incapable...

  6. 21 CFR 872.6710 - Boiling water sterilizer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Boiling water sterilizer. 872.6710 Section 872.6710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6710 Boiling water sterilizer. (a) Identification. A boiling water sterilizer is an...

  7. 21 CFR 872.6710 - Boiling water sterilizer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Boiling water sterilizer. 872.6710 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6710 Boiling water sterilizer. (a) Identification. A boiling water sterilizer is an AC-powered device that consists of a container for boiling...

  8. 21 CFR 872.6710 - Boiling water sterilizer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Boiling water sterilizer. 872.6710 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6710 Boiling water sterilizer. (a) Identification. A boiling water sterilizer is an AC-powered device that consists of a container for boiling...

  9. The Coercive Sterilization of Aboriginal Women in Canada

    ERIC Educational Resources Information Center

    Stote, Karen

    2012-01-01

    This paper considers the coercive sterilization of Aboriginal women in legislated and non-legislated form in Canada. I provide an historical and materialist critique of coercive sterilization. I argue for coercive sterilization to be understood as one of many policies employed to undermine Aboriginal women, to separate Aboriginal peoples from…

  10. 9 CFR 116.4 - Sterilization and pasteurization -records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sterilization and pasteurization... REPORTS § 116.4 Sterilization and pasteurization -records. Records shall be made by means of automatic... ingredients, equipment, or biological product subjected to sterilization or pasteurization. (Approved by the...

  11. 9 CFR 116.4 - Sterilization and pasteurization -records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sterilization and pasteurization... REPORTS § 116.4 Sterilization and pasteurization -records. Records shall be made by means of automatic... ingredients, equipment, or biological product subjected to sterilization or pasteurization. (Approved by the...

  12. Committee opinion no. 530: access to postpartum sterilization.

    PubMed

    2012-07-01

    Postpartum tubal sterilization is one of the safest and most effective methods of contraception. Women who desire this type of sterilization typically undergo thorough counseling and informed consent during prenatal care and reiterate their desire for postpartum sterilization at the time of their hospital admission. Not all women who desire postpartum sterilization actually undergo the surgical procedure, and women with unfulfilled requests for postpartum sterilization have a high rate of repeat pregnancy (approaching 50%) within the following year. Potentially correctable barriers to obtaining postpartum sterilization include patient and health care provider factors, as well as hospital and health care system issues. Given the consequences of a missed procedure and the limited time frame in which it may be performed, postpartum sterilization should be considered an urgent surgical procedure. In addition, women with government insurance face barriers to sterilization procedures based on cumbersome consent requirements. The differences in the requirements surrounding consent for sterilization procedures based on the type of insurance a patient has must be addressed in order to establish fair and equitable access to sterilization procedures for all women. Policies and procedures that remove barriers to and increase efficiency in performing postpartum sterilization could reduce cancellations of the procedure. Improving consistency in accomplishing desired postpartum sterilization is an important strategy to reduce high rates of unintended pregnancy in the United States.

  13. MSI's unique, multi-functional contract sterilization facility

    NASA Astrophysics Data System (ADS)

    Morganstern, Kennard H.

    Medical Sterilization Inc. is a unique company supplying sterilization services to regional hospitals in the New York area and also providing contract sterilization and radiation processing services to industry. The evolution from a concept to an operational entity is reviewed in this report.

  14. The Coercive Sterilization of Aboriginal Women in Canada

    ERIC Educational Resources Information Center

    Stote, Karen

    2012-01-01

    This paper considers the coercive sterilization of Aboriginal women in legislated and non-legislated form in Canada. I provide an historical and materialist critique of coercive sterilization. I argue for coercive sterilization to be understood as one of many policies employed to undermine Aboriginal women, to separate Aboriginal peoples from…

  15. 21 CFR 522.1484 - Neomycin sulfate sterile solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1...

  16. 21 CFR 522.1484 - Neomycin sulfate sterile solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1...

  17. 21 CFR 522.1484 - Neomycin sulfate sterile solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1...

  18. 21 CFR 522.1484 - Neomycin sulfate sterile solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1...

  19. Suppression of Pest Lepidoptera by Releasing Partially Sterile Males

    ERIC Educational Resources Information Center

    Knipling. E. F.

    1970-01-01

    Uses population growth models to calculate the theoretical suppression of reproduction achieved by releasing irradiated male moths carrying genetic sterility factors. Shows that releasing partially sterile males should be more effective than releasing fully sterile males. Discusses the costs and advantages of applying this approach to the control…

  20. Suppression of Pest Lepidoptera by Releasing Partially Sterile Males

    ERIC Educational Resources Information Center

    Knipling. E. F.

    1970-01-01

    Uses population growth models to calculate the theoretical suppression of reproduction achieved by releasing irradiated male moths carrying genetic sterility factors. Shows that releasing partially sterile males should be more effective than releasing fully sterile males. Discusses the costs and advantages of applying this approach to the control…

  1. Development of male-sterile lines for breeding hybrid rice

    USDA-ARS?s Scientific Manuscript database

    Rice is a self-pollinated crop that depends on male-sterility for F1 hybrid seed production. As an alternative to accessing existing male-sterile lines from other hybrid breeding programs, the program in Arkansas has created its own novel male-sterile sources. These were developed out of germplasm...

  2. 21 CFR 872.6710 - Boiling water sterilizer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Boiling water sterilizer. 872.6710 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6710 Boiling water sterilizer. (a) Identification. A boiling water sterilizer is an AC-powered device that consists of a container for boiling...

  3. 21 CFR 872.6710 - Boiling water sterilizer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Boiling water sterilizer. 872.6710 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6710 Boiling water sterilizer. (a) Identification. A boiling water sterilizer is an AC-powered device that consists of a container for boiling...

  4. 21 CFR 880.6860 - Ethylene oxide gas sterilizer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO)...

  5. 21 CFR 880.6860 - Ethylene oxide gas sterilizer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO)...

  6. 21 CFR 880.6860 - Ethylene oxide gas sterilizer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO)...

  7. 21 CFR 880.6860 - Ethylene oxide gas sterilizer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO)...

  8. 21 CFR 880.6860 - Ethylene oxide gas sterilizer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO)...

  9. Sterilization project offers model for better care.

    PubMed

    Finger, W R

    1993-08-01

    India's experiences with sterilization indicate that quality of care is an essential feature of appropriate, voluntary family planning services. Good quality of care reduces the problems associated with services and increases client's acceptability and continuation rates. The Center for Excellence in India has established a model that emphasis matching the right method with each client's circumstances. The model first developed standards, which were based on international guidelines and expertise, and then developed and implemented a training program for providers; finally, a quality assurance system was established in order to promote compliance with standards. At present, there is not 100% agreement among international guidelines on standards for sterilization or other methods. In 1992, Family Health International (FHI) published a comparison on 8 major sets of service, delivery, guidelines, and were used around the world; FHI world wide variations in guidelines. A USAID study group is currently reviewing scientific evidence on oral contraceptives, injectables, Norplant, and IUDS. There is difficulty in reaching international consensus and even greater difficulty in changing approaches and policies of specific countries. It is much easier to institute quality of care issues at the beginning of program development or when methods are first introduced. In India, the Centers of Excellence program developed its own national standards on sterilization, and the resulting document is specifically suited to India. The standards emphasize the client's choice and human issues such as counseling and communication. Sterilization reversal, which is not always successful, will be provided, even though sterilization will be promoted as a permanent procedure. 4 regional centers have been set up through medical colleges in Delhi, Calcutta, Bombay and Madras. 12 additional state level centers will be established in the future. Good training was considered an essential part of the

  10. Coelioscopic and Endoscope-Assisted Sterilization of Chelonians.

    PubMed

    Proença, Laila M; Divers, Stephen J

    2015-09-01

    Elective sterilization is a safe and well-established surgical procedure performed in dogs and cats worldwide. Conversely, chelonian sterilization has been mostly performed therapeutically, because of the intricate anatomy and difficult access to the reproductive organs, and consequently, reproductive problems and diseases remain common. With the advance of veterinary endoscopy, novel techniques of soft tissue prefemoral coelioscopic and endoscope-assisted sterilization have been published, and preventative chelonian sterilization is now a reality. Nevertheless, extrapolations between species should be carefully considered, and further studies are warranted. This article summarizes and describes the current coelioscopic and coelioscope-assisted sterilization techniques for chelonia. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Modelling releases of sterile mosquitoes with different strategies.

    PubMed

    Li, Jia; Yuan, Zhiling

    2015-01-01

    To prevent the transmissions of malaria, dengue fever, or other mosquito-borne diseases, one effective weapon is the sterile insect technique in which sterile mosquitoes are released to reduce or eradicate the wild mosquito population. To study the impact of the sterile insect technique on disease transmission, we formulate discrete-time mathematical models, based on difference equations, for the interactive dynamics of the wild and sterile mosquitoes, incorporating different strategies in releasing sterile mosquitoes. We investigate the model dynamics and compare the impact of the different release strategies. Numerical examples are given to demonstrate rich dynamical features of the models.

  12. A double inductively coupled plasma for sterilization of medical devices

    NASA Astrophysics Data System (ADS)

    Halfmann, H.; Bibinov, N.; Wunderlich, J.; Awakowicz, P.

    2007-07-01

    A double inductively coupled low pressure plasma for sterilization of bio-medical materials is introduced. It is developed for homogeneous treatment of three-dimensional objects. The short treatment times and low temperatures allow the sterilization of heat sensitive materials like ultra-high-molecular-weight-polyethylene or polyvinyl chloride. Using a non-toxic atmosphere reduces the total process time in comparision with common methods. Langmuir probe measurements are presented to show the difference between ICP- and CCP-mode discharges, the spatial homogeneity and the influence on the sterilization efficiency. To know more about the sterilization mechanisms optical emission is measured and correlated with sterilization results.

  13. Application of a Dense Gas Technique for Sterilizing Soft Biomaterials

    PubMed Central

    Karajanagi, Sandeep S.; Yoganathan, Roshan; Mammucari, Raffaella; Park, Hyoungshin; Cox, Julian; Zeitels, Steven M.; Langer, Robert; Foster, Neil R.

    2017-01-01

    Sterilization of soft biomaterials such as hydrogels is challenging because existing methods such as gamma irradiation, steam sterilization, or ethylene oxide sterilization, while effective at achieving high sterility assurance levels (SAL), may compromise their physicochemical properties and biocompatibility. New methods that effectively sterilize soft biomaterials without compromising their properties are therefore required. In this report, a dense-carbon dioxide (CO2)-based technique was used to sterilize soft polyethylene glycol (PEG)-based hydrogels while retaining their structure and physicochemical properties. Conventional sterilization methods such as gamma irradiation and steam sterilization severely compromised the structure of the hydrogels. PEG hydrogels with high water content and low elastic shear modulus (a measure of stiffness) were deliberately inoculated with bacteria and spores and then subjected to dense CO2. The dense CO2-based methods effectively sterilized the hydrogels achieving a SAL of 10−7 without compromising the viscoelastic properties, pH, water-content, and structure of the gels. Furthermore, dense CO2-treated gels were biocompatible and non-toxic when implanted subcutaneously in ferrets. The application of novel dense CO2-based methods to sterilize soft biomaterials has implications in developing safe sterilization methods for soft biomedical implants such as dermal fillers and viscosupplements. PMID:21337339

  14. A search for sterile neutrinos in MINOS

    SciTech Connect

    Osiecki, Thomas Henry

    2007-01-01

    MINOS, the Main Injector Neutrino Oscillation Search, is a long baseline neutrino oscillation experiment based at Fermilab National Accelerator Laboratory. The experiment uses a neutrino beam, which is measured 1 km downstream from its origin in the Near detector at Fermilab and then 735 km later in the Far detector at the Soudan mine. By comparing these two measurements, MINOS can attain a very high precision for parameters in the atmospheric sector of neutrino oscillations. In addition to precisely determining Δm$2\\atop{23}$ and θ23 through the disappearance of vμ, MINOS is able to measure vμ → vsterile by looking for a deficit in the number of neutral current interactions seen in the Far detector. In this thesis, we present the results of a search for sterile neutrinos in MINOS.

  15. [Sterile insect technique: targeted control without insecticide].

    PubMed

    Boyer, S

    2012-03-01

    Sterile insect technique (SIT) is a method of disease vector control technique that consists of releasing overwhelming numbers of sterile males. This method provides an environmentally friendly alternative to insecticides. Another advantage of SIT in comparison with other methods is to provide a targeted species-specific approach. In Reunion Island, SIT has been proposed as a basis for developing a viable method of vector control against Aedes albopictus and Anopheles arabiensis. The technique has already been successfully tested on fly and mosquito species for more than 40 years. The CRVOI (Centre de Recherche et de Veille sur les Maladies Emergentes dans l'Océan Indien) is carrying out studies to determine the feasibility of SIT for control of Anopheles arabiensis (vector of malaria) and Aedes albopictus (vector of chikungunya and dengue) on Reunion Island and other islands in the Indian Ocean region.

  16. Daughters mimic sterile neutrinos (almost!) perfectly

    NASA Astrophysics Data System (ADS)

    Hasenkamp, Jasper

    2014-09-01

    Since only recently, cosmological observations are sensitive to hot dark matter (HDM) admixtures with sub-eV mass, mhdmeff < eV, that are not fully-thermalised, Δ Neff < 1. We argue that their almost automatic interpretation as a sterile neutrino species is neither from theoretical nor practical parsimony principles preferred over HDM formed by decay products (daughters) of an out-of-equilibrium particle decay. While daughters mimic sterile neutrinos in Neff and mhdmeff, there are opportunities to assess this possibility in likelihood analyses. Connecting cosmological parameters and moments of momentum distribution functions, we show that—also in the case of mass-degenerate daughters with indistinguishable main physical effects—the mimicry breaks down when the next moment, the skewness, is considered. Predicted differences of order one in the root-mean-squares of absolute momenta are too small for current sensitivities.

  17. Can sterile neutrinos be the dark matter?

    PubMed

    Seljak, Uros; Makarov, Alexey; McDonald, Patrick; Trac, Hy

    2006-11-10

    We use the Ly-alpha forest power spectrum measured by the Sloan Digital Sky Survey and high-resolution spectroscopy observations in combination with cosmic microwave background and galaxy clustering constraints to place limits on a sterile neutrino as a dark matter candidate in the warm dark matter scenario. Such a neutrino would be created in the early Universe through mixing with an active neutrino and would suppress structure on scales smaller than its free-streaming scale. We ran a series of high-resolution hydrodynamic simulations with varying neutrino masses to describe the effect of a sterile neutrino on the Ly-alpha forest power spectrum. We find that the mass limit is m(s) >13 keV at 95% C.L. (9 keV at 99.9%), which is above the upper limit allowed by x-ray constraints, excluding this candidate from being all of the dark matter in this model.

  18. Light Sterile Neutrino Search at Daya Bay

    NASA Astrophysics Data System (ADS)

    Ling, Jiajie; Daya Bay Collaboration

    2014-09-01

    It has been well established through neutrino oscillation that neutrinos have masses and their flavors mix. In 2012, The Daya Bay Reactor Neutrino Experiment discovered that the last unknown neutrino mixing angle θ13 is non-zero. With more than one million reactor antineutrino interactions recorded since December 2011, besides the most precise measurement of sin2 2θ13 , the Daya Bay experiment also has high sensitivity in sterile neutrino search due to its multiple baselines. In this talk, I will discuss the spectral analysis of the light sterile neutrino search in the largely unexplored region of 10-3 eV2 < | Δm2 | < 0 . 3 eV2 at Daya Bay through the electron antineutrino disappearance channel.

  19. Light sterile neutrinos and inflationary freedom

    SciTech Connect

    Gariazzo, S.; Giunti, C.; Laveder, M. E-mail: giunti@to.infn.it

    2015-04-01

    We perform a cosmological analysis in which we allow the primordial power spectrum of scalar perturbations to assume a shape that is different from the usual power-law predicted by the simplest models of cosmological inflation. We parameterize the free primordial power spectrum with a ''piecewise cubic Hermite interpolating polynomial'' (PCHIP). We consider a 3+1 neutrino mixing model with a sterile neutrino having a mass at the eV scale, which can explain the anomalies observed in short-baseline neutrino oscillation experiments. We find that the freedom of the primordial power spectrum allows to reconcile the cosmological data with a fully thermalized sterile neutrino in the early Universe. Moreover, the cosmological analysis gives us some information on the shape of the primordial power spectrum, which presents a feature around the wavenumber k=0.002 Mpc{sup −1}.

  20. A Sterile Robotic Mars Soil Analyzer

    NASA Technical Reports Server (NTRS)

    Levin, Gilbert V.; Miller, Joseph D.; Straat, Patricia Ann; Hoover, Richard E.

    2002-01-01

    Since the 1976 Viking Mission to Mars, follow-on efforts to resolve its controversial life detection results have been thwarted by two heretofore insurmountable difficulties: the huge expense of sterilizing the entire spacecraft to protect the integrity of life detection experiments; and the lack of a practical robotic life detection package that could produce results acceptable as unambiguous by the scientific community. We here present a method that assures sterility and the complete integrity of robotic life detection experiments, all at a negligible cost. Second, we propose a candidate set of integrated, highly sensitive experiments that we believe could produce results acceptable to the vast majority of scientists. In addition to the biology-chemistry issue, the extensively debated oxidative state of the Martian surface and other chemical and physical characteristics of the Martian soil would be determined. We present our concept for a miniaturized instrument that could carry out a number of candidate experiments to achieve the objective.

  1. Psychosexual adjustment following sterilization: a prospective study on Chinese women.

    PubMed

    Tang, C S; Chung, T K

    1997-02-01

    The present study aimed to identify significant predictors of Chinese women's psychosexual adjustment after sterilization. One hundred fifteen multiparous Chinese women, aged 25-51 years, were interviewed before and after elective laparoscopic or postpartum sterilization. Eight-seven women were also interviewed about their pshychosexual adjustment at 1 year after sterilization. Results showed that the fear of negative evaluation by others, family cohesion and adaptability, and preoperative psychological distress were robust predictors of adverse psychosexual outcome immediately and 1 year after sterilization. There was significant improvement in women's mental health following sterilization, and their sexual adjustment such as coital frequency and sexual satisfaction were not adversely affected at 1 year follow-up. Women with either elective or postpartum sterilization had similar adjustment throughout, except the latter group tended to experience more physical discomfort at 1 year follow-up. About 3.4% of the women experienced regret at 12 months after sterilization.

  2. The sterilization efficacy of reprocessed single use diathermy pencils.

    PubMed

    Batista Neto, Simone; Graziano, Kazuko Uchikawa; Padoveze, Maria Clara; Kawagoe, Júlia Yaeko

    2010-01-01

    In Brazil, single use diathermy pencils (SUDP) are among the most common reused devices. This study assesses the sterilization efficacy of reprocessing SUDP using two cleansing methods (manual or automated), followed by one of three of the low-temperature sterilization methods: Hydrogen Peroxide Plasma (HPP), Ethylene Oxide (ETO) or Low-Temperature Steam Formaldehyde (LTSF). The sample was composed of 360 SUDP after their first use. The probability of sterilization failure was estimated considering the number of positive microbiological results obtained by cultures of the studied devices. The overall sterilization failure probability for SUDP was 0.26. The sterilization method, which presented the lowest failure probability was the LTSF (0.01), followed by ETO (0.21) and HPP (0.56). Automated cleansing obtained a better result than manual cleansing. This trial demonstrated that the probability of sterilization in reprocessed SUDP is highly dependent on both the type of cleansing and the sterilization method applied.

  3. Portable Chemical Sterilizer (PCS) for Surgical Instruments

    DTIC Science & Technology

    2004-12-01

    reactions, either individually or in combination, to effect sterilization of contaminated objects. The first system is a scaled up version of the...production by chemical reaction Ti quantities of heat, steam, and chlorine dioxide are produce that act in concert to effect the destruction of the...contaminating microorganisms. In fact, the conditions of heat and humidity created inside the PCS intensify the effectiveness of ClO2 as a lethal

  4. Mechanism for ordinary-sterile neutrino mixing

    SciTech Connect

    Langacker, P.

    1998-11-01

    Efficient oscillations between ordinary (active) and sterile neutrinos can occur only if Dirac and Majorana mass terms exist which are both small and comparable. It is shown that this can occur naturally in a class of string models, in which higher-dimensional operators in the superpotential lead to an intermediate scale expectation value for a scalar field and to suppressed Dirac and Majorana fermion masses. {copyright} {ital 1998} {ital The American Physical Society}

  5. Sterile neutrinos in the early universe

    SciTech Connect

    Malaney, R.A. ); Fuller, G.M. . Dept. of Physics)

    1990-11-14

    We discuss the role played by right-handed sterile neutrinos in the early universe. We show how well known {sup 4}He constraint on the number of relativistic degrees of freedom at early times limits the equilibration of the right handed neutrino sea with the background plasma. We discuss how this allows interesting constraints to be placed on neutrino properties. In particular, a new limit on the Dirac mass of the neutrino is presented. 12 refs.

  6. A Flash Sterilizer using Peracetic Acid

    DTIC Science & Technology

    1976-07-01

    REPORT 7606 / A FLASH STERILIZER USING PERACETIC ACID H. BRUCE CRANFORD, JR. C Reproduced From Best Available Copy US ARMY MEDICAL BIOENGINEERING...Operating Room area whereby an accidentally contaminated Instrument can be * rapidly resterilized using peracetic acid and returned to use was designedand...Pvoperties of Peracetic Acid 5 S..Proposed Design Approach 6 "Equipment 11 SUMM•ARY 17 BIBLIOGRAPHY 19 A*?ENDICES 23 A. Ltr, HQDA. (SGRD-SDM), WASH, DC, A-1

  7. Thermal In-Pouch Microwave Sterilization

    DTIC Science & Technology

    2012-01-09

    chicken piece placed at the cold spot in chicken- dumpling pouches at the end of complete thermal process. PA 3679 # 308 Clos- tridium sporogenes spore ...crop was used to calculate average D-values for the dif- ferent temperatures and determine the z-value of PA 3679 spores in chicken breast. Process...the developed MW sterilization processing delivered expected lethality to C. sporogenes PA 3679 spores . Forty chicken-dumpling pouches processed in

  8. Study on the role of active radicals on plasma sterilization inside small diameter flexible polymeric tubes

    NASA Astrophysics Data System (ADS)

    Mstsuura, Hiroto; Fujiyama, Takatomo; Okuno, Yasuki; Furuta, Masakazu; Okuda, Shuichi; Takemura, Yuichiro

    2015-09-01

    Recently, atmospheric pressure discharge plasma has gathered attention in various fields. Among them, plasma sterilization with many types of plasma source has studied for decades and its mechanism is still an open question. If active radicals produced in plasma has main contribution of killing bacterias, direct contact of the so-called plasma flame might not be necessary. To confirm this, sterilization inside small diameter flexible polymeric tubes is studied in present work. DBD type plasma jet is produce by flowing helium gas in a glass tube. A long polymeric tube is connected and plasma jet is introduced into it. Plasma flame length depends on helium gas flow rate, but limited to about 10 cm in our experimental condition. E.colis set at the exit plasma source is easily killed during 10 min irradiation. At the tube end (about 20 cm away from plasma source exit), sterilization is possible with 30 min operation. This result shows that active radical is produced with helium plasma and mist contained in sample, and it can be transferred more than 20 cm during it life time. More plasma diagnostic data will also be shown at the conference. This work was partially supported by the ''ZE Research Program, IAE(ZE27B-4).

  9. Sterilization of women: benefits vs risks.

    PubMed

    Rioux, J E

    Voluntary sterilization is the birth control method most widely practiced throughout the world. The last ten years have witnessed great improvements in techniques and perfection of innovations, explaining the important role that it now plays in the regulation of fertility. Different methods are examined and it is concluded that hysterectomy is the best, if medically indicated; conventional laparotomy is not justified unless required by concomitant intraabdominal pathology; minilaparotomy is mostly suitable postpartum; colpotomy is better left to specialists; laparoscopy is ideal for nonpregnant patients; culdoscopy is a relic of the past; and hysteroscopy, although still experimental, may be the way of the future. The advantages of voluntary sterilization lie in its remarkable and immediate efficiency, freedom from ongoing motivation, the convenience of a one-time operation, the absence of side effects and the reduction of total costs. Its disadvantages are the complexity of any surgical intervention for a woman, its indisputable finality, its uncertain legality and the risks inherent in any operation. Hysterectomy and tubal ligation are practically never fatal, so this argument does not influence the choice of either method. However, incidence of morbidity is higher following hysterectomies, which must therefore be justified. The balance is clearly in favor of voluntary sterilization for the woman who is convinced that the size of her family is complete.

  10. Sterilization of laparoscopes. Is soaking sufficient?

    PubMed

    Corson, S L; Block, S; Mintz, C; Dole, M; Wainwright, A

    1979-08-01

    Controversy exists over the proper methods of sterilizing laparoscopic telescopes. An edict requiring gas sterilization rather than solution soaking of these instruments is in force in all federal hospitals. This rule has necessitated capital investments for new instruments and has led to a severe reduction in the number of cases of laparoscopy that may be scheduled in one day. Fear of contamination is based on theoretical considerations and rusn counter to the actual, observed safety record seen with laparoscopes soaked in activated glutaraldehyde between cases. In an effort to dispassionately approach this problem, cultures of the umbilical area, the laparoscope and the pelvic serosal surfaces were taken to document the type of organisms commonly encountered under clinical conditions. Cultures for aerobic and anaerobic bacteria as well as for fungi were taken after soaking the telescope in activated glutaraldehyde. The results demonstrated growth of common skin organisms even after skin preparation with povidone-iodine and ethyl alcohol. Similar organisms were recovered in some cases from the laparoscope and the pelvic surfaces. The actual degree of contamination suggested by a colony count falls well within the range of the healthy peritoneum to cope with these organisms. Recommendations for laparoscopic sterilization or disinfection are based on the results obtained.

  11. Plasma sterilization using the RF glow discharge

    NASA Astrophysics Data System (ADS)

    Yang, Liqing; Chen, Jierong; Gao, Junling; Guo, Yafei

    2009-08-01

    In the present work, glow discharge oxygen plasma was used to sterilize the Pseudomonas aeruginosa on the polyethylene terephthalate (PET) sheets. In a self-designed plasma reaction equipment, active species (electron, ion, radical, UV light, etc.) were separated effectively, and the discharge area, afterglow area and remote area were plotted out in the plasma field. Before and after plasma treatment the cell morphology was studied by scanning electron microscopy (SEM). The results showed that after treatment of 30 s the germicidal effect is 4.26, 3. 84, 2.61, respectively in the three areas on the following conditions: discharge power was 40 W and gas flux was 20 cm 3/min. SEM results revealed the cell morphology before and after plasma treatment. The walls or cell membrane cracking was testified by determining the content of protein using coomassie light blue technique. The results from electron spin resonance spectroscopy (ESR) and double Langmuir electron probe showed that electron, ion and oxygen free radical played important roles in sterilization in the discharge area, but only oxygen radicals acted to sterilize the bacteria in the afterglow area and the remote area.

  12. Sterile Neutrino Search with the PROSPECT Experiment

    NASA Astrophysics Data System (ADS)

    Surukuchi Venkata, Pranava Teja

    2017-01-01

    PROSPECT is a multi-phased short-baseline reactor antineutrino experiment with primary goals of performing a search for sterile neutrinos and making a precise measurement of 235U reactor antineutrino spectrum from the High Flux Isotope Reactor at Oak Ridge National Laboratory. PROSPECT will provide a model independent oscillation measurement of electron antineutrinos by performing relative spectral comparison between a wide range of baselines. By covering the baselines of 7-12 m with Phase-I and extending the coverage to 19m with Phase-II, the PROSPECT experiment will be able to address the current eV-scale sterile neutrino oscillation best-fit region within a single year of data-taking and covers a major portion of suggested parameter space within 3 years of Phase-II data-taking. Additionally, with a Phase-II detector PROSPECT will be able to distinguish between 3+1 mixing, 3+N mixing and other non-standard oscillations. In this talk, we describe the PROSPECT oscillation fitting framework and expected detector sensitivity to the oscillations arising from eV-scale sterile neutrinos. DOE

  13. Post-ablation-tubal sterilization syndrome.

    PubMed

    Townsend, D E; McCausland, V; McCausland, A; Fields, G; Kauffman, K

    1993-09-01

    To determine the cause of unilateral or bilateral pelvic pain associated with vaginal spotting in women who had previously undergone tubal ligation followed by roller-ball endometrial ablation. Women who had undergone previous tubal sterilization followed by rollerball endometrial ablation were evaluated laparoscopically and hysteroscopically when they presented with a symptom complex of intermittent vaginal bleeding associated with severe cramping pain in the lower abdomen. During a 1.5-year observation period, six women with the symptom complex had laparoscopy and hysteroscopy. In all cases, marked endometrial scarring was noted. In every case, the proximal portions of either one or both fallopian tubes were swollen, and two cases had the appearance of an early ectopic pregnancy. In the remaining cases, the fallopian tubes were rubbery and swollen to as much as twice normal size. Symptoms in five of six patients subsided after laparoscopic removal of the oviduct. It appears that women who have had a tubal sterilization followed by endometrial ablation are at risk of developing an ectopic-like symptom complex. Salpingectomy appears to be effective in relieving symptoms. Whether this represents a new syndrome or just an unusual association between tubal sterilization and endometrial ablation remains to be seen.

  14. Radiation Sterilization of Prototype Military Foods

    PubMed Central

    Anellis, Abe; Berkowitz, D.; Jarboe, C.; El-Bisi, H. M.

    1967-01-01

    Ten lots of diced cured ham, packed in cans, were inoculated with approximately 106Clostridium botulinum spores per can. Each lot was seeded with a different strain (five type A and five type B strains). All cans were irradiated to various dose levels with Co60. Evidence provided by swelling, toxicity, and recoverable C. botulinum with 6,350 cans demonstrated that: (i) 4.5 Mrad was more than adequate as a sterilization dose; (ii) the minimal experimental sterilizing dose (ESD) based on nonswollen nontoxic endpoints was 2.0 < ESD ≤ 2.5 Mrad, and based on non-spoiled sterile cans was 3.0 < ESD ≤ 3.5 Mrad (the latter was supported by the computed theoretical 12D dose); (iii) D values calculated from botulinal survival data indicated that, as a group, the type A strains were more radioresistant than type B strains; strains 12885A and 41B, with respective D values of 0.242 and 0.175, represented the most resistant of each type; (iv) swollen cans did not always contain toxin, nor were toxic cans always swollen; (v) viable C. botulinum can exist for 6 months at 30 C without producing visible or toxic spoilage at doses of 3.0 Mrad and lower, including, in some instances, 0.0 Mrad; and (vi) a phenomenon similar to heat activation of spores occurred at sublethal radiation doses. Images Fig. 1 PMID:5340164

  15. [Principles of antisepsis, disinfection and sterilization].

    PubMed

    Hernández-Navarrete, María-Jesús; Celorrio-Pascual, José-Miguel; Lapresta Moros, Carlos; Solano Bernad, Victor-Manuel

    2014-12-01

    This article aims to provide a brief review of the main concepts on which the prevention and control of infection are based. Antisepsis comprises a set of techniques aimed at the total sterilization, or at most, disinfection, removing germs that contaminate an environment. Both procedures must be preceded by an environmental cleanup in the location in which they intend to be applied. The disinfection is carried out using biocides or germicides. Antimicrobial chemicals, that have mechanisms of action and resistances very similar to antibiotics, are generating concern due to the possibility of crossing genetic information that aggravates the problem of bacterial resistance. Most biocides can act as antiseptics, and applied to skin tissue, or disinfectants on inanimate materials. The spectrum of action of germicides depends on the product itself and external controllable factors: temperature, concentration, exposure time, etc. Sterilization techniques are primarily physical, by exposing the material to steam, or sterilizing gas, using autoclaves. Major advances are the use of low temperatures with shorter exposure times, in parallel with technological advances in instrumentation in order to avoid high temperatures and high use rotations due to workload. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Sterile neutrinos as subdominant warm dark matter

    SciTech Connect

    Palazzo, A.; Cumberbatch, D.; Slosar, A.; Silk, J.

    2007-11-15

    In light of recent findings which seem to disfavor a scenario with (warm) dark matter entirely constituted of sterile neutrinos produced via the Dodelson-Widrow mechanism, we investigate the constraints attainable for this mechanism by relaxing the usual hypothesis that the relic neutrino abundance must necessarily account for all of the dark matter. We first study how to reinterpret the limits attainable from x-ray nondetection and Lyman-{alpha} forest measurements in the case that sterile neutrinos constitute only a fraction f{sub s} of the total amount of dark matter. Then, assuming that sterile neutrinos are generated in the early universe solely through the Dodelson-Widrow mechanism, we show how the x-ray and Lyman-{alpha} results jointly constrain the mass-mixing parameters governing their production. Furthermore, we show how the same data allow us to set a robust upper limit f{sub s} < or approx. 0.7 at the 2{sigma} level, rejecting the case of dominant dark matter (f{sub s}=1) at the {approx}3{sigma} level.

  17. Theory of oscillations and sterile neutrinos

    NASA Astrophysics Data System (ADS)

    Palazzo, Antonio

    2014-11-01

    We present a concise review of the theoretical status of neutrino oscillations within the (standard) 3-flavor framework and the (non-standard) 4-flavor scheme endowed with one additional sterile species (the so-called 3+1 scheme). We emphasize the slight overall preference that recently emerged for CP-violation in the 3-flavor analysis and highlight the unique role of the global data combination in the near future. After a brief introduction of the motivations for light (eV) sterile neutrinos, we discuss the bounds on their mixing with the electron neutrinos, attainable from the solar sector. The upper limit so obtained is independent of the reactor neutrino fluxes, whose calculations are affected by systematic uncertainties not completely under control. Finally, we highlight the possibility to explore sub-eV "super-light" sterile neutrinos exploiting the θ13-dedicated reactor experiments also commenting on the robustness of the 3- flavor results within the enlarged 3+1 scheme.

  18. Dental burs and endodontic files: are routine sterilization procedures effective?

    PubMed

    Morrison, Archie; Conrod, Susan

    2009-02-01

    The complex miniature architecture of dental burs and endodontic files makes precleaning and sterilization difficult. Devising a sterilization protocol for endodontic files and dental burs requires care, and some have suggested that these instruments be considered single-use devices. One purpose of this study was to determine the effectiveness of various sterilization techniques currently used in dentistry for the resterilization of dental burs and endodontic files. The second aim was to determine whether new dental burs and endodontic files, as supplied in packages from the manufacturer, are sterile. The sterility of new (unused) and used dental burs and endodontic files before and after various sterilization procedures was analyzed. New burs and files were tested immediately after removal from manufacturers" packaging, with or without prior sterilization. Burs and files that had been used in various dental offices were precleaned, packaged, resterilized and then tested for various pathogens. Each item was individually removed from the sterilization packaging, transferred by sterile technique into Todd-Hewitt broth, incubated at 37 degrees C for 72 hours and observed for bacterial growth. Sterilization procedures were 100% effective for unused burs and unused files but were less than 100% effective for all other test groups. Contamination rates following sterilization ranged from 15% for one group of used burs (p = 0.01) to 58% for one group of used files (p < 0.001). Dental burs and endodontic files, as packaged by the manufacturer, are not sterile and should therefore be sterilized before first use. The resterilization procedures tested here were not adequate, and more rigorous sterilization procedures are needed. If such procedures cannot be devised, these instruments should perhaps be considered single-use devices.

  19. Surgical sterilization: an underutilized procedure for evaluating the merits of induced sterility

    USGS Publications Warehouse

    Kennelly, James J.; Converse, Kathryn A.

    1993-01-01

    Despite more than 4 decades of effort, development of effective wildlife damage control programs based on sterilization of target species has met with limited success. This is partly due to the fact that investigators have assumed, rather than empirically tested, whether the reproductive strategies of the target populations were vulnerable to the planned treatment. Equally important, methods selected to include sterility usually involve a chemical agent that can affect sociosexual behaviors of the nuisance population. In this report, we illustrate how surgically induced sterility circumvents both problems--how the concept without the potentially confounding secondary effects of a chemical. We assessed the merits of initiating research to develop a male chemosterilant for Norway rats, red-winged blackbirds, beaver, and Canada geese by inducing sterility surgically. The infidelity of many red-winged females to their polygynous territorial male was surprising and argued against searching for a male sterilant. On the other hand, beaver and Canada goose studies confirmed previous reports that both form par-bonds and are monogamous. Both should be vulnerable to a male chemosterilant approach, and research toward this goal is justified.

  20. [Calcium distribution in fertile and sterile anthers of a genic male sterile Chinese cabbage].

    PubMed

    Xie, Chao-Tian; Yang, Yan-Hong; Qiu, Yi-Lan; Ge, Li-Li; Tian, Hui-Qiao

    2005-12-01

    Potassium antimonite was used to locate calcium in the fertile and sterile anthers of a genic male sterile Chinese cabbage (Brassica campestris L. ssp. chinensis Makino) to probe the relation between Ca(2+) and fertility and sterility of anthers of the cabbage. During fertile anther development, calcium granules increase in number in anther wall cells after meiosis, and then appeared also in locule, suggesting a calcium influx into locule from anther wall cells (Plate I-4). Then the number of calcium granules in microspore cytoplasm also increased at early stage (Plate II-1), accumulated mainly on the membrane of small vacuoles which were fusing to form big ones to make a polarity in the cell and to prepare asymmetric division of microspore (Plate II-3,4). After microspore division and the big vacuole decomposition, many calcium granules accumulated again on the membrane of the vacuoles (Plate III-1,2), displaying calcium regulates vacuole formation and decomposition during pollen development. In sterile anthers, abnormal distribution of calcium granules first appeared in callus wall of microspore mother cell (Plate IV-1). However, only a few calcium granules appeared in early microspores, which then could not form small vacuoles and finally a big vacuole (Plate IV-2,3). The aborting microspores degenerate by cytoplasm shrinking (Plate IV-5,6). The difference pattern of distribution of calcium granules between the fertile and sterile anthers indicates that anomalies in the distribution of calcium accumulation are correlated with the failure of pollen development and pollen abortion.