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Sample records for adherent lymphokine-activated killer

  1. Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases

    Basse, P; Herberman, R B; Nannmark, U; Johansson, B R; Hokland, M; Wasserman, K; Goldfarb, R H

    1991-01-01

    While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or...... carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45...... tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung...

  2. Tissue distribution of adoptively transferred adherent lymphokine-activated killer cells assessed by different cell labels

    Basse, P; Herberman, R B; Hokland, M;

    1992-01-01

    alternative direct visual methods for identification of the injected cells, such as fluorescent dyes (rhodamine and H33342) or immunohistochemical staining of asialo-GM1-positive cells. The number of i.v. injected A-LAK cells found in the liver by all visual methods ranged from 1% to 5% of the injected dose...... staining of asialo-GM1-positive cells appear to be reliable and essentially equivalent methods for investigations of the fate of adoptively transferred A-LAK cells. Using these methods, we found that only few A-LAK cells redistribute to the liver upon i.v., i.e. systemic, injection, whereas 40%-50% of......Assessment of the tissue distribution of adoptively transferred adherent lymphokine-activated killer A-LAK) cells by use of 51Cr indicated that these effector cells, after an initial phase in the lungs, distributed in high numbers to liver and spleen (30% and 10% of injected dose, respectively...

  3. Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells

    1983-01-01

    Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.

  4. In vivo distribution and tissue localization of highly purified rat lymphokine-activated killer (LAK) cells

    A highly purified population of effector lymphokine-activated killer (LAK) cells was generated by culturing nylon-wool column nonadherent rat splenocytes in the presence of interleukin 2 (IL-2), and the cells which became adherent to the plastic flasks were separated and maintained in culture for a total of 5 days. More than 95% of these cells had the morphology of large granular lymphocytes (LGL), expressed surface phenotypes characteristic of rat natural killer (NK) cells, and were able to kill NK-sensitive and NK-resistant tumor target cells. 51Cr-labeled purified A-LAK cells injected intravenously into syngeneic F344 rats localized primarily in the lungs 2 hr after injection but then redistributed to the liver and the spleen by 24 hr after injection. The effects of various immunological manipulations on the distribution pattern of the isolated LAK cells were evaluated. Treatment of the host with 500 rad total body X-irradiation 24 hr before cell injection resulted in an early uptake of LAK cells into the liver and the spleen, whereas treatment with cyclophosphamide 1 day before cell injection, resulted in an early uptake of LAK cells into the liver but not into the spleen. Treatment of the recipient rats with up to 120,000 units recombinant interleukin-2 intraperitoneally did not result in the accumulation of LAK cells at the site of IL-2 injection, nor did it result in a modulation of the overall distribution pattern or total recovery of radiolabeled LAK cells. Rather, the administration of IL-2 was necessary to maintain the cytotoxic activity of the injected LAK cells isolated from the liver and spleen

  5. Scintigraphy with In-111 labeled lymphokine-activated killer cells of malignant brain tumor

    Itoh, Kazuo; Sawamura, Yutaka; Hosokawa, Masuo; Kobayashi, Hiroshi

    This study was undertaken to assess the in vivo distribution and migration of lymphokine-activated killer (LAK) cells to the target malignant foci in four patients with advanced malignant brain tumor. All four patients had failed to respond to prior adoptive immunotherapy. After the intravenous administration of radiolabeled LAK cells, most of the radiolabeled cells were distributed in the liver and spleen, with lesser radioactivity in the lung and bone marrow. Scintigraphy revealed the target malignant foci in all four patients to be areas of increased radioactivity. The number of radiolabeled LAK cells that accumulated in the intracranial malignant lesions, however, seemed to be insufficient to mediate regression of the solid tumor mass by direct cell-to-cell interaction. We conclude that the failure of adoptive immunotherapy could be accounted for by the poor migration of infused LAK cells to the target malignant foci. We also conclude that radionuclide study with radiolabeled lymphokine-activated culture cells against tumors is likely to be helpful as a means to investigate effective possibilities for subsequent adoptive immunotherapy.

  6. Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma

    Manning, L.S.; Bowman, R.V.; Davis, M.R.; Musk, A.W.; Robinson, B.W. (Queen Elizabeth II Medical Centre, Nedlands (Australia))

    1989-10-01

    Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM (n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls (n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 +/- 3% lysis by controls vs 34 +/- 3% lysis by patients with MM, P less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 +/- 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.

  7. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

    Schellhorn, Melina; Haustein, Maria; Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-01-01

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, ...

  8. Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells

    The authors previously reported that the adoptive transfer of lymphokine-activated killer (LAK) cells plus repetitive injections of recombinant interleukin 2 (IL 2) produced a marked reduction in established pulmonary metastases from a variety of murine sarcomas. The requirement for the exogenous administration of IL 2 prompted a subsequent examination of the role of IL 2 in the in vivo function of transferred LAK cells. The in vivo proliferation and migration patterns of lymphoid cells in C57BL/6 mice were examined after i.v. transfer of LAK cells alone, i.p. injection of IL 2 alone, or the combination of LAK cells and IL 2. A model for in vivo labeling of the DNA of dividing cells was used in which mice were injected with 5-[125I]-iodo-2'-deoxyuridine (125IUdR) and, 20 hr later, their tissues were removed and were counted in a gamma analyzer. A proliferation index (PI) was calculated by dividing the mean cpm of organs of experimentally treated mice by the mean cpm of organs of control mice. In animals given LAK cells alone, the lungs and liver demonstrated little if any uptake of 125IUdR above saline-treated controls, whereas the same organs of mice receiving 6000 U of IL 2 alone displayed higher radiolabel incorporation. When mice were given LAK cells plus 6000 U of IL 2, their tissues showed an additional increase in 125IUdR uptake

  9. Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors

    Nakagawa, Kunio; Kamezaki, Takao; Shibata, Yasushi; Tsunoda, Takashi; Meguro, Kotoo; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    1995-01-01

    The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors. (author).

  10. Cytotoxic mechanisms of murine lymphokine-activated killer cells: functional and biochemical characterization of homogeneous populations of spleen LAK cells.

    Zychlinsky, A; Joag, S; Liu, C C; Young, J D

    1990-04-01

    A highly purified population of murine lymphokine-activated killer (LAK) cells was obtained by selecting plastic-adherent splenocytes after incubation in high doses of recombinant IL-2. The population obtained was shown to be more than 95% positive for the cell marker asialo-GM1, and negative for both Lyt-1 (CD5) and Lyt-2 (CD8). The cells presented typical large granular lymphocyte morphology, and killed NK-susceptible target cells in an exclusively calcium-dependent fashion. A target cell DNA fragmentation activity of LAK cells could be detected even before target cell death. The presence of Hanukkah Factor/granzyme A/serine esterase 1, CTLA-1/granzyme B/serine esterase 2, and pore-forming protein (PFP/perforin) in these LAK cells was demonstrated by Northern blot analysis, suggesting that these markers are not exclusively associated with cytotoxic T lymphocytes. On immunoblots, antibodies specific for a lymphocyte PFP/perforin reacted with a 70-kDa protein of LAK cells. PFP/perforin was localized by immunofluorescence to the cell granules. A 50-kDa protein antigenically related to the macrophage cytokine tumor necrosis factor (TNF) was detected by immunoblotting and localized by immunofluorescence to both the cell granules and the cytosol. No RNA for TNF, however, could be detected using TNF-specific probes, suggesting that LAK cells may contain a cytotoxic factor which is related to, but distinct from, TNF. The work presented here demonstrates that cytotoxic mediators identified in cell lines are also present in primary cell cultures. PMID:1690083

  11. Characterization of lymphokine-activated killer cells from peripheral blood and lymph nodes of non-Hodgkin's lymphoma patients

    Peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) from non-Hodgkin's lymphoma patients were tested for lymphokine-activated killer cells (LAK) cells cytotoxicity using appropriate targets in a short-term 51chromium-release assay. The results showed a significant depression in LNL-LAK activity suggesting the reduced capacity of LNL to generate LAK cells. LNL-LAK cells demonstrated significantly low percentages of cells expressing CD16, CD56 and CD25 as compared to PBL-LAK and healthy donors. The reduced capacity to generate LAK cells in lymph nodes could by due to the presence of low numbers of natural killer cells which are thought to be the main precursors of LAK cells. The IL-2 producing ability of lymph node mononuclear cells was found to by significantly higher than that of peripheral blood mononuclear cells from both healthy donors and and NHL patients. (author)

  12. Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts

    Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant. In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively, as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites

  13. Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells

    1987-01-01

    Interleukin 4 (IL-4) expresses multiple biologic activities, including B cell, mast cell, and T cell stimulation. We showed that the incubation of resting splenocytes from C57BL/6 mice solely in purified native or recombinant mouse IL-4 results in the generation of lymphokine-activated killer (LAK) activity directed against fresh, syngeneic sarcoma cells. The precursor activated by IL-4 expresses surface asialo-GM1. In addition, IL-4 is capable of amplifying the splenic LAK activity induced b...

  14. Influence of transfusion of lymphokine-activated T killer cells on inflammatory responses in dogs after laparotomy.

    Mie, Keiichiro; Tomihari, Mizuki; Hoshi, Kiyotaka; Nakamura, Takashi; Yamaguchi, Tomohiro; Miyahara, Kazuro; Shimada, Terumasa

    2016-05-01

    The influence of transfusion of lymphokine-activated T killer cells (T-LAK) on inflammatory responses was examined in dogs after laparotomy. Plasma C-reactive protein (CRP) level, cell numbers of peripheral blood lymphocytes (PBLs) and T lymphocyte subsets (CD3(+), CD4(+) and CD8(+)) and mRNA expression levels of cytokines including interleukin (IL)-2, IL-12, IL-4, IL-10 and transforming growth factor (TGF)-β in peripheral blood mononuclear cells (PBMCs) were measured in dogs with (T-LAK group) or without (control group) a single T-LAK administration immediately after laparotomy. The plasma CRP level initially increased and then decreased to the normal range at 7 days after laparotomy in the T-LAK group, which was earlier than in the control group. The expression level of IL-10 mRNA showed a marked postoperative increase and was significantly higher than the preoperative level on day 7 (Pimmunity related to cytokine production by PBMCs. PMID:26727638

  15. Induction of lymphokine-activated killer-like cells by cancer chemotherapy

    1988-01-01

    Natural cell-mediated cytotoxicity against NK-resistant target tumor cells was found in the peripheral blood of tumor-bearing patients approximately 1 mo after combined chemotherapy. The recognition specificity of these effector cells was broad and had no restriction. From the experiments of negative selection with mAbs and complements, these newly developed killer cells after chemotherapy were thought to be LAK-like cells. Contribution of these LAK-like cells to the mechanism of action of an...

  16. Anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells

    Our previous studies demonstrated that the incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (RIL 2) resulted in the generation of lymphokine-activated killer (LAK) cells capable of lysing a broad spectrum of fresh tumors in short-term chromium-release assays. Moreover, injections of LAK cells plus RIL 2 were highly effective in eliminating established 3 day metastases in the lung and liver. We have examined several parameters to define whether or not the cytolytic activity of LAK cells as measured in vitro correlated directly with the in vivo anti-tumor efficacy of adoptively transferred LAK cells. LAK cells plus RIL 2 could mediate marked reductions of established pulmonary metastases in mice rendered T cell deficient by adult thymectomy and lethal, total body irradiation followed by reconstitution with T cell-depleted bone marrow and spleen cells. Thus there was no requirement for additional T lymphocytes of host origin for successful therapy with adoptively transferred LAK cells plus RIL 2. Fresh splenocytes depleted of T cells by anti-Thy-1.2 monoclonal antibody plus complement generated LAK cells that were as highly lytic to fresh tumor in vitro and were as effective in reducing established pulmonary metastases as those generated from untreated or complement-treated splenocytes. Thus, the precursor to LAK cells with anti-tumor activity in vitro and in vivo did not express the Thy-1 antigenic marker. In contrast, treatment of LAK effector cells (those generated from a 3-day incubation of fresh, normal splenocytes in RIL 2) with anti-Thy-1.2 antibody plus complement reduced or abolished their in vitro cytolytic activity

  17. Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model

    A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC)

  18. Interleukin-2 (rIL-2)-induced lymphokine-activated killer (LAK) cells and their precursors express the VGO1 antigen

    Precursor and effector cells of recombinant interleukin-2 (r-IL-2)-induced lymphokine-activated killer (LAK) activity were investigated for their expression of VGO1. Peripheral blood lymphocytes (PBL) from normal donors were purified and separated in a FACS 420 into VGO1+- and VGO1- cell fractions before and after culture for 96 hr with 100 U/ml of r-IL-2. Their lytic activity against K 562 and Daudi cells was measured in a 51Cr release assay. The majority, if not all, of the LAK effector and precursor cells was VGO1+ lymphocytes. The expression of VGO1 by LAK precursor cells remained stable under the culture conditions used in our experiments. VGO1- lymphocytes cultured with r-IL-2 demonstrated neither LAK-induced activity nor expression of VGO1 antigen

  19. Change in peripheral blood lymphocyte count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells combined with palliative tumor resection.

    Mie, Keiichiro; Shimada, Terumasa; Akiyoshi, Hideo; Hayashi, Akiyoshi; Ohashi, Fumihito

    2016-09-01

    We evaluated changes in peripheral blood lymphocyte (PBL) count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells (T-LAK) in combination with surgery. Fifteen tumor-bearing dogs treated with T-LAK therapy combined with palliative resection of tumors were enrolled in the present study. T-LAK were generated from autologous peripheral blood mononuclear cells (PBMC) by culture with recombinant human interleukin -2 (rhIL-2) and solid phase anti-canine cluster of differentiation (CD)3 antibody. T-LAK were administrated intravenously at 2-4-week intervals. After the first administration of T-LAK, counts of PBL and T lymphocyte subsets (CD3(+), CD4(+) and CD8(+) cells) increased and the CD4/CD8 ratio decreased, with significant increases in CD8(+) cells (P<0.05). In 8 tumor-bearing dogs that were administered sequential T-LAK, available data on changes in PBL and T lymphocyte phenotypes until the fifth administration were also analyzed. In tumor-bearing dogs administered 5 rounds of T-LAK, CD8(+) cell counts were maintained high until the fifth administration of T-LAK. Moreover, the CD4/CD8 ratio remained low until the fifth administration of T-LAK. These results indicate that T-LAK therapy combined with surgery may increase peripheral blood T lymphocytes, particularly CD8(+) cells, in tumor-bearing dogs. PMID:27436446

  20. Requirement of T-lymphokine-activated killer cell-originated protein kinase for TRAIL resistance of human HeLa cervical cancer cells

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-κB activity. Furthermore, expression of NF-κB-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-κB activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.

  1. Immunotherapy of murine sarcomas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2

    Interleukin-2 (IL-2) at high doses or at low doses in concert with lymphokine-activated killer (LAK) cells can produce regression of established pulmonary and hepatic metastases from a variety of tumors in mice. IL-2 appears to mediate its antitumor effect through the generation of LAK cells in vivo from endogenous lymphocytes and by the stimulation of host and transferred LAK cell proliferation in tissues. In this paper we have investigated different strategies for IL-2 administration to determine which regimen produced maximal in vivo proliferation and optimal immunotherapeutic efficacy of LAK cells. Tissue expansion of lymphoid cells was assessed using an assay of in vivo labeling of dividing cells by the thymidine analogue, 5-[125I]iododeoxyuridine. The therapeutic effect of the different IL-2 administration protocols was determined by evaluating their efficacy in the treatment of established, 3-day pulmonary metastases from sarcomas in mice. The selection of IL-2 injection regimens for evaluation was based upon pharmacokinetic studies of IL-2 in mice. A single i.v. or i.p. dose yielded high peak IL-2 levels that could be measured for only a few hours after injection, while IL-2 given i.p. thrice daily produced titers that were detectable throughout the study periods (greater than or equal to 6 units/ml of serum after 100,000 units of IL-2 i.p. thrice daily). Using the proliferation and therapy models, we tested the same cumulative daily doses of IL-2 administered by i.v. or i.p. once daily, or i.p. thrice daily regimens. The i.p. thrice daily protocol stimulated greater lymphoid cell proliferation in the lungs, for example, than did the other regimens

  2. Human lymphokine-activated killer cell system. V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes

    Culture of human peripheral blood lymphocytes (PBL) in purified natural or recombinant interleukin 2 in the absence of exogenous antigen or mitogen causes the differentiation of nonlytic precursor cells into lymphokine-activated killers (LAK). A titration of purified Jurkat IL-2 (BRMP, FCRC, NIH) IL-2 showed that the relatively low concentration of 5 U/ml was optimal for LAK activation. When the responding PBL were pretreated with either mitomycin C or gamma irradiation, LAK activation did not occur, indicating that proliferation, in addition to differentiation, is required. The spectrum of target cells susceptible to LAK lysis in a 4-hr chromium-51-release assay includes fresh NK-resistant tumor cells and trinitrophenyl (TNP)-modified autologous PBL. Unmodified PBL are not lysed. Cold target inhibition studies indicated that LAK lysis of autologous TNP-PBL is totally inhibited by fresh tumors cells, and that tumor lysis is inhibited by TNP-PBL. Additionally, allogeneic tumors totally inhibit lysis of autologous tumor cells in other cold target studies. These results demonstrate that the lytic activity expressed by LAK is not HLA restricted, is not limited to tumor cells, and is polyspecific as indicated by the cross-reactive recognition of multiple target cell types in these cold target inhibition studies

  3. Anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo

    The authors showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after the i.v. injection of syngeneic tumor cells in C57BL/6 mice. In this report, they analyzed the factors required for successful therapy. Titration analysis in vivo revealed an inverse relationship between the number of pulmonary metastases remaining after treatment and both the number of LAK cells and the amount of RIL 2 administered. Fresh or unstimulated splenocytes had no anti-tumor effect; a 2- to 3-day incubation of splenocytes in RIL 2 was required. LAK cells generated from allogeneic DBA (H-2d) splenocytes were as effective in vivo as syngeneic, C57BL/6 (H-2b) LAK cells. The anti-metastatic capacity of LAK cells was significantly reduced or eliminated when irradiated with 3000 rad before adoptive transfer. The combined therapy of LAK cells plus RIL 2 was shown to be highly effective in mice immunosuppressed by 500 rad total body irradiation and in treating macrometastases established in the lung 10 days after the i.v. injection of sarcoma cells. Further, reduction of both micrometastases and macrometastases could also be achieved by RIL 2 alone when administered at higher levels than were required with LAK cells. The value of LAK cell transfer and of IL 2 administration for the treatment of tumors established at other sites is currently under investigation

  4. Isolation and purification of natural killer cells subpopulations using mononuclear cells

    Mosaffa N

    1999-06-01

    Full Text Available Natural Killer (NK cells are the main lymphocyte population expressing P75 B chain of the IL-2 receptor (IL-2R. Consequently, incubation of peripheral blood lymphocytes with IL-2 induce selective activation of NK cells and results in NK activity and generation of Lymphokine activated killer (LAK cells activity and proliferation. One of the early events during IL-2 activation of peripheral blood lymphocyte in both rodents and humans is adherence of some NK cells to plastic surface. The cells adherence to plastic after 24 hr of culture with IL-2 are almost exclusively CD56+, have the morphology large granular cells to yield a highly entiched population of activated NK cells that have been used for systemic adoptive immunotherapy. To test these hypothesis, we used highly purified population of human peripheral NK cells through the biological and nonimmunclogical phenotyping technique. Blood mononuclear cells were separated by centrifugation of ficol-hypaque gradient from normal blood donor (20-30 years age. We depleted after purification of nonadherent cells with nylonwool. We collected with rosette technique to remove cells with high affinity SRBC receptors. These cells separate in two parts A-NK and NA-NK by mononuclear celss activated supernatant media. The main objective results of this study show that the subpopulation of human NK cell which develope early adherent to plastic surface in the presence of supernatant mononuclear celss activation media was functionally more cytotoxic and killed K562 targets in single cell sytotoxicity manner and LDH activity assay than nonadherent NK cells and resting NK cells

  5. THE EFFECT OF PHENYLACETATE ON THE EXPANSION AND CYTOTOXIC ACTIVITY OF ADHERENT LAK CELLS FROM PATIENTS WITH HEPATOCELLULAR CARCINOMA

    郑宁; 叶胜龙; 孙瑞霞; 赵燕; 汤钊猷

    2002-01-01

    Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods:\tA-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.

  6. Adherence to HeLa cells, typing by killer toxins and susceptibility to antifungal agents of Candida dubliniensis strains Adesão a células HeLa, tipagem pelas toxinas "killer" e sensibilidade a antifúngicos de cepas de Candida dubliniensis

    Gismari Miranda da Silva

    2007-03-01

    Full Text Available The aim of this study was to evaluate the adherence capability to HeLa cells, the susceptibility to killer toxins and the in vitro susceptibility to antifungal agents (eTest? method - AB Biodisk, Solna, Sweden of 9 Candida dubliniensis isolates recovered from HIV+ and AIDS patients. The adherence test was strongly positive for strain ATCC 777 and positive for all other strains. Typing by killer toxins revealed two different biotypes among the 9 isolates studied: 888 and 688. Only biotype 688 (ATCC 777 was susceptible to the K2 toxin. There was a significant inverse correlation between adherence and killer toxin susceptibility (r = -0.8525 - p = 0.0035. No strains presented resistance to fluconazole, itraconazole, ketoconazole, voriconazole, flucytosine or amphotericin-B. With the exception of ATCC 777, all the other isolates presented similar behavior.O objetivo do presente trabalho foi avaliar o comportamento de cepas de Candida dubliniensis recuperadas de pacientes HIV+ e com AIDS por meio da pesquisa de capacidade de adesão a células HeLa, susceptibilidade a toxinas "Killer" e resistência in vitro a antifúngicos (eTest® AB Biodisk, Solna, Suécia. O ensaio de adesão foi fortemente aderente para a amostra padrão ATCC 777, e aderente para os demais isolados. Os testes de tipagem das amostras frente às cepas-padr��o produtoras de toxinas "Killer" mostraram dois biótipos diferentes dos 9 isolados estudados: 888 e 688. Somente o biótipo 688 (ATCC 777 de C. dubliniensis foi sensível à toxina K2. Houve correlação inversa significativa entre adesão e sensibilidade a toxinas "killer" (r = -0,8525 - p = 0,0035. Em relação à pesquisa de resistência a antifúngicos, as amostras de C. dubliniensis foram sensíveis ao fluconazol, itraconazol, cetoconazol, voriconazol, à flucitosina e anfotericina B. Com exceção da amostra ATCC 777, todas as demais mostraram comportamento similar.

  7. Present and future of allogeneic natural killer cell therapy

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  8. The Mechanism of Organophosphorus Pesticide-Induced Inhibition of Cytolytic Activity of Killer Cells

    Qing Li; Tomoyuki Kawada

    2006-01-01

    The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect immune responses including effects on antibody production, IL-2 production,T cell proliferation, decreasement of CD5 cells, and increasement of CD26 cells and autoantibodies. However, there have been few papers investigating the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews the new mechanism of OP-induced inhibition of activities of natural killer (NK),lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL). NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain perforin, granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas !igand (Fas-L)/Fas pathway. To date, it has been reported that OPs inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes, and by decreasing the intracellular level of perforin, granzyme A and granulysin, which was mediated by inducing degranulation of NK cells and by inhibiting the transcript of mRNA of perforin, granzyme A and granulysin; 2)OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional; 3) OPs induce apoptosis of immune cells.

  9. Killer "Killer Examples" for Design Patterns

    Caspersen, Michael Edelgaard; Alphonce, Carl; Decker, Adrienne

    2007-01-01

    Giving students an appreciation of the benefits of using design patterns and an ability to use them effectively in developing code presents several interesting pedagogical challenges. This paper discusses pedagogical lessons learned at the "Killer Examples" for Design Patterns and Objects First s...

  10. Grass and weed killer poisoning

    ... medlineplus.gov/ency/article/002838.htm Grass and weed killer poisoning To use the sharing features on this page, please enable JavaScript. Many weed killers contain dangerous chemicals that are harmful if swallowed. ...

  11. Rethinking adherence.

    Steiner, John F

    2012-10-16

    In 2012, the Centers for Medicare & Medicaid Services (CMS) will introduce measures of adherence to oral hypoglycemic, antihypertensive, and cholesterol-lowering drugs into its Medicare Advantage quality program. To meet these quality goals, delivery systems will need to develop and disseminate strategies to improve adherence. The design of adherence interventions has too often been guided by the mistaken assumptions that adherence is a single behavior that can be predicted from readily available patient characteristics and that individual clinicians alone can improve adherence at the population level.Effective interventions require recognition that adherence is a set of interacting behaviors influenced by individual, social, and environmental forces; adherence interventions must be broadly based, rather than targeted to specific population subgroups; and counseling with a trusted clinician needs to be complemented by outreach interventions and removal of structural and organizational barriers. To achieve the adherence goals set by CMS, front-line clinicians, interdisciplinary teams, organizational leaders, and policymakers will need to coordinate efforts in ways that exemplify the underlying principles of health care reform. PMID:23070491

  12. Biology Myth-Killers

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  13. Suppressing the killer instinct.

    Campbell, Kerry S

    2016-01-01

    Natural killer (NK) cells are innate lymphoid cells that have adopted activating and inhibitory signaling mechanisms enabling them to be tolerant of normal cells but to distinguish and eliminate tumor cells and virus-infected cells. In this issue of Science Signaling, Matalon et al show how inhibitory receptors disrupt NK cell activation by stimulating dephosphorylation of the adaptor protein LAT (linker of activated T cells) and phospholipase C-γ by the phosphatase SHP-1 [Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1], as well as ubiquitylation of LAT by Cbl family E3 ubiquitin ligases. PMID:27221707

  14. HIV Medication Adherence

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  15. Effects of Ganoderma lucidum polysaccharides on proliferation and cytotoxicity of cytokine-induced killer cells

    Xiao-ling ZHU; Zhi-bin LIN

    2005-01-01

    Aim: To study the effects (and the mechanisms thereof) of Ganoderma lucidum polysaccharides (Gl-PS) on the proliferation and the anti-tumor activity of cytokineinduced killer (CIK) cells, and to make use of CIK cells as a means to investigate the interactions between Gl-PS and cytokines. Methods: CIK cells were prepared by using the standard protocol as a positive control. Experimental groups also underwent the standard protocol, except that Gl-PS (400 mg/L or 100 mg/L) was added and the dose of anti-CD3 and interleukin-2 they received was reduced by 50% and 75%, respectively. For negative controls, Gl- PS in the experimental protocol was replaced with soluble starch or methylcellulose (400 mg/L or 100 mg/L).CIK cell proliferation, cytotoxicity, and phenotype weredetermined by using the Trypan blue exclusion method, MTT assay, and flow cytometry. Results: By synergizing cytokines, Gl-PS (400 mg/L or 100 mg/L) could decrease the amount of cytokine in lymphokine activated killer (LAK) cells and CIK cells culture, but had no significant effect on the proliferation, cytotoxicity, or phenotype of LAK cells, or CIK cells induced by cytokines at higher doses alone, in which CIK cells expanded about 80-fold and the main effectors, CD3+NK1.1+ cells, expanded by more than 15%. The cytotoxicity of CIK cells in experimental groups was 79.3%±4.7%, 76.9%±6.8% versus the positive control 80.7%±6.8% against P815 (P>0.05)and 88.9%±5.5%, 84.7%±7.9% versus the positive control 89.8%±4.5% against YAC-1 (P>0.05). The activity of Gl-PS could mostly be blocked by anti-CR3.Conclusion: Gl-PS was shown to be a promising biological response modifier and immune potentiator. The effect of Gl-PS on CIK cells is possibly mediated primarily through complement receptor type 3.

  16. Arsenic: The Silent Killer

    Foster, Andrea (USGS)

    2006-02-28

    Andrea Foster uses x-rays to determine the forms of potentially toxic elements in environmentally-important matrices such as water, sediments, plants, and microorganisms. In this free public lecture, Foster will discuss her research on arsenic, which is called the silent killer because dissolved in water, it is colorless, odorless, and tasteless, yet consumption of relatively small doses of this element in its most toxic forms can cause rapid and violent death. Arsenic is a well-known poison, and has been used as such since ancient times. Less well known is the fact that much lower doses of the element, consumed over years, can lead to a variety of skin and internal cancers that can also be fatal. Currently, what has been called the largest mass poisoning in history is occurring in Bangladesh, where most people are by necessity drinking ground water that is contaminated with arsenic far in excess of the maximum amounts determined to be safe by the World Health Organization. This presentation will review the long and complicated history with arsenic, describe how x-rays have helped explain the high yet spatially variable arsenic concentrations in Bangladesh, discuss the ways in which land use in Bangladesh may be exacerbating the problem, and summarize the impact of this silent killer on drinking water systems worldwide.

  17. Natural killer cells in psoriasis.

    Tobin, A M

    2012-02-01

    Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-alpha, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known to be involved in psoriatic lesions, natural killer and natural killer T cells appear to have a unique role. We review the evidence supporting a role for natural killer cells in psoriasis.

  18. Killer Whale Genetic Data - Southern resident killer whale pedigree analysis

    National Oceanic and Atmospheric Administration, Department of Commerce — In this project, we are using genetic variation to infer mating patterns in the southern killer whale community. In Canada, this population was listed as threatened...

  19. Adherence to Antidepressant Medication

    Åkerblad, Ann-Charlotte

    2007-01-01

    Non-adherence to medication is a major obstacle in the treatment of depression. The objectives of the present study were to explore the effect of two interventions aiming to increase antidepressant treatment adherence, and to examine long-term consequences and costs of depression in adherent and non-adherent primary care patients. A randomised controlled design was used to assess the respective effects of a written educational adherence enhancing programme and therapeutic drug monitoring in ...

  20. Keiko, Killer Whale. [Lesson Plan].

    Discovery Communications, Inc., Bethesda, MD.

    This lesson plan presents activities designed to help students understand that Keiko, the killer whale, lived for a long time in an aquarium and had to be taught to live independently; and that computer users can get updates on how Keiko is doing. The main activity of the lesson involves middle school students working in small groups to produce a…

  1. Killer whale prey - Determining prey selection by southern resident killer whales (SRKW)

    National Oceanic and Atmospheric Administration, Department of Commerce — Prey selectivity by southern resident killer whales is being determined by analyses of fish scales and tissue from predation events and feces. Information on killer...

  2. An Industrial THz Killer Application?

    van Mechelen, Dook

    2015-01-01

    Terahertz technology is mature enough for large-volume sensing applications. However, Dook van Mechelen says there are a few hurdles preventing its industrial debut. THz spectroscopy has a number of advantages that point to abundant industrial applications, in areas such quality control, security and biomedical imaging. Yet despite those advantages, the search for a THz "killer application"--a novel, innovative use with a business case strong enough to bring the technology into the industrial mainstream--has remained fruitless, and even the hope of finding such an application has begun to falter. Why has a killer app for THz radiation been so elusive? And how can the road to industrial application of this versatile technology be cleared?

  3. An Industrial THz Killer Application?

    van Mechelen, Dook

    2015-01-01

    Terahertz technology is mature enough for large-volume sensing applications. However, Dook van Mechelen says there are a few hurdles preventing its industrial debut. THz spectroscopy has a number of advantages that point to abundant industrial applications, in areas such quality control, security and biomedical imaging. Yet despite those advantages, the search for a THz "killer application"--a novel, innovative use with a business case strong enough to bring the technology into the industrial...

  4. Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed

    Serebrovskaya, Ekaterina O.; Ryumina, Alina P.; Boulina, Maria E.; Shirmanova, Marina V.; Zagaynova, Elena V.; Bogdanova, Ekaterina A.; Lukyanov, Sergey A.; Lukyanov, Konstantin A.

    2014-07-01

    KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane-localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Time-lapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis.

  5. Adherence to antidepressants

    Abimbola Farinde

    2013-01-01

    Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.

  6. Structural Basis for Phototoxicity of the Genetically Encoded Photosensitizer KillerRed

    Pletnev, Sergei; Gurskaya, Nadya G.; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Chudakov, Dmitri M.; Martynov, Vladimir I.; Popov, Vladimir O.; Kovalchuk, Mikhail V.; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Vladimir; (SOIBC); (Russ. Acad. Sci.); (NCI)

    2009-11-23

    KillerRed is the only known fluorescent protein that demonstrates notable phototoxicity, exceeding that of the other green and red fluorescent proteins by at least 1,000-fold. KillerRed could serve as an instrument to inactivate target proteins or to kill cell populations in photodynamic therapy. However, the nature of KillerRed phototoxicity has remained unclear, impeding the development of more phototoxic variants. Here we present the results of a high resolution crystallographic study of KillerRed in the active fluorescent and in the photobleached non-fluorescent states. A unique and striking feature of the structure is a water-filled channel reaching the chromophore area from the end cap of the {beta}-barrel that is probably one of the key structural features responsible for phototoxicity. A study of the structure-function relationship of KillerRed, supported by structure-based, site-directed mutagenesis, has also revealed the key residues most likely responsible for the phototoxic effect. In particular, Glu68 and Ser119, located adjacent to the chromophore, have been assigned as the primary trigger of the reaction chain.

  7. Notorious Cases of Serial Killers

    Iosub Elena-Cătălina

    2014-05-01

    Full Text Available The reconstruction of a death scene provides an overall picture of the crime and will indicate the murder as an event or one of a series of events and also the criminal. But when the criminal is declared a serial killer, many questions are raised up. How could a person kill some else without a reason or why people react in such a disorganized way and become so brutal or what made them act like that and so many questions with also so many answers. This project explains the psychology of a murderer, his own way of thinking and acting by presuming that we may accurately discover what is in their minds when they kill. It is about a very complex issue regarding murder investigations, biological factors and psychological profile of a serial killer. Dealing with this problem we will at last reach to the question that could solve finally the puzzle: ―Are serial murderers distorted reflections of society's own values?

  8. Persistence in the shadow of killers.

    Sinclair, Robert M

    2014-01-01

    Killing is perhaps the most definite form of communication possible. Microbes such as yeasts and gut bacteria have been shown to exhibit killer phenotypes. The killer strains are able to kill other microbes occupying the same ecological niche, and do so with impunity. It would therefore be expected that, wherever a killer phenotype has arisen, all members of the population would soon be killers or dead. Surprisingly, (1) one can find both killer and sensitive strains in coexistence, both in the wild and in in vitro experiments, and (2) the absolute fitness cost of the killer phenotype often seems to be very small. We present an explicit model of such coexistence in a fragmented or discrete environment. A killer strain may kill all sensitive cells in one patch (one piece of rotting fruit, one cave or one human gut, for example), allowing sensitives to exist only in the absence of killer strains on the same patch. In our model, populations spread easily between patches, but in a stochastic manner: one can imagine spores borne by the wind over a field of untended apple trees, or enteric disease transmission in a region in which travel is effectively unrestricted. What we show is that coexistence is not only possible, but that it is possible even if the absolute fitness advantage of the sensitive strain over the killer strain is arbitrarily small. We do this by performing a specifically targeted mathematical analysis on our model, rather than via simulations. Our model does not assume large population densities, and may thus be useful in the context of understanding the ecology of extreme environments. PMID:25071753

  9. Deficient natural killer cell function in preeclampsia

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour 51Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder

  10. Deficient natural killer cell function in preeclampsia

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  11. Construction of Killer Wine Yeast Strain

    Seki, Tetsuji; Choi, Eon-Ho; Ryu, Dewey

    1985-01-01

    A double-stranded RNA plasmid which confers the superkiller phenotype was transferred into a wine yeast (Montrachet strain 522) and its leucine-requiring derivative (strain 694) by cytoduction, using the protoplast fusion technique. The killer wine yeast constructed completely suppressed the growth of killer-sensitive strains of Saccharomyces cerevisiae in yeast extract-peptone-glucose medium at pH 4.5, whereas the killer effect was somewhat decreased at pH 3.5. The wine yeast harboring the k...

  12. Natural killer cells in leukemogenesis

    In order to relate a reduced natural killer (NK) cell function to leukemogenesis, NK cells in the spleen and peritoneal exudate cells, with and without stimulation by Corynebacterium parvum, were tested in mice of various strains after split dose irradiation and after leukemogenic treatment with butyl- and methylnitrosourea. The investigations included also mice submitted to non-leukemogenic irradiation (1 x 1.5 and 1 x 4.5 Gy) and mice submitted to an additional treatment with hydrocortisone, which delays leukemia development after methylnitrosourea. There was, indeed, a NK-cell depression, but no major differences were seen between mice prone to leukemia development and those after cytotoxic, but nonleukemogenic, treatment. (author)

  13. Natural killer cell activity during measles.

    Griffin, D E; Ward, B J; Jauregui, E; Johnson, R T; Vaisberg, A

    1990-01-01

    Natural killer cells are postulated to play an important role in host anti-viral defences. We measured natural killer cell activity in 30 individuals with acute measles (73 +/- 21 lytic units (LU)/10(7) cells) and 16 individuals with other infectious diseases (149 +/- 95 LU) and found it reduced compared with values for adults (375 +/- 70 LU; P less than 0.001) or children (300 +/- 73 LU, P less than 0.01) without infection. Reduced natural killer cell activity was found in measles patients with (84 +/- 30 LU) and without (55 +/- 18 LU) complications and was present for at least 3 weeks after the onset of the rash. Activity was increased by in vitro exposure of cells to interleukin-2. Depressed natural killer cell activity parallels in time the suppression of other parameters of cell-mediated immunity that occurs during measles. PMID:1696863

  14. Killer whales and whaling: the scavenging hypothesis

    Whitehead, Hal; Reeves, Randall

    2005-01-01

    Killer whales (Orcinus orca) frequently scavenged from the carcasses produced by whalers. This practice became especially prominent with large-scale mechanical whaling in the twentieth century, which provided temporally and spatially clustered floating carcasses associated with loud acoustic signals. The carcasses were often of species of large whale preferred by killer whales but that normally sink beyond their diving range. In the middle years of the twentieth century floating whaled carcas...

  15. Persistence in the Shadow of Killers

    Robert Michael Sinclair

    2014-07-01

    Full Text Available Killing is perhaps the most definite form of communication possible. Microbes such as yeasts and gutbacteria have been shown to exhibit killer phenotypes. The killer strains are able to kill othermicrobes occupying the same ecological niche, and do so with impunity. It would therefore beexpected that, wherever a killer phenotype has arisen, all members of the population would soon bekillers or dead. Surprisingly, (i one can find both killer and sensitive strains in coexistence, both inthe wild and in in-vitro experiments, and (ii the absolute fitness cost of the killer phenotype oftenseems to be very small. We present an explicit model of such coexistence in a fragmented or discreteenvironment. A killer strain may kill all sensitive cells in one patch (one piece of rotting fruit, onecave or one human gut, for example, allowing sensitives to exist only in the absence of killer strainson the same patch. In our model, populations spread easily between patches, but in a stochasticmanner: One can imagine spores borne by the wind over a field of untended apple trees, or entericdisease transmission in a region in which travel is effectively unrestricted. What we show is thatcoexistence is not only possible, but that it is possible even if the absolute fitness advantage of thesensitive strain over the killer strain is arbitrarily small. We do this by performing a specificallytargeted mathematical analysis on our model, rather than via simulations. Our model does not assumelarge population densities, and may thus be useful in the context of understanding the ecology ofextreme environments.

  16. Adherence to Sublingual Immunotherapy.

    Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia

    2016-02-01

    Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865

  17. DETERMINATION OF KILLER CHARACTER OF WINE YEAST ISOLATED FROM ISTRA

    Sandi ORLIC; POGAČIĆ, Martina; Ana JEROMEL; Marko KAROGLAN; Kozina, Bernard; IACUMIN, Lucilla; Redžepović, Sulejman

    2008-01-01

    Wild wine yeasts with killer phenotype are widespread in many wine regions of the world. The presence of killer yeasts may become particularly important in wine fermentations conducted by inoculation with selected strains of Saccharomyces cerevisiae. Wild killer yeasts may suppress selected sensitive yeasts inoculated into the must during the fermentation. The goal of this investigation was to identify killer yeast in Istra region using physiological and molecular methods. In total 50 S.cerev...

  18. Killer toxin from a novel killer yeast Pichia kudriavzevii RY55 with idiosyncratic antibacterial activity.

    Bajaj, Bijender Kumar; Raina, Sandeepu; Singh, Satbir

    2013-08-01

    The killer phenomenon of yeast may have technological implications in many areas like beverage fermentation, food technology, biological control in agriculture, and in medicine. In the present study the killer phenomenon in Pichia kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P. kudriavzevii RY55 toxin exhibited excellent antibacterial activity against several pathogens of human health significance such as Escherichia coli, Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity by using ammonium sulphate precipitation and ion exchange chromatography and characterized for few properties. P. kudriavzevii RY55 killer toxin may be of vast significance in the development of novel antimicrobial chemotherapeutic agents, new bio-based safer candidates for food preservation and biocontrol, and starter cultures for fermentation industries. PMID:22961241

  19. Medication adherence in the elderly

    Angela Frances Yap, BSc (Pharm) (Hons); Thiru Thirumoorthy, MBBS, FRCP (London), FAMS; Yu Heng Kwan, BSc (Pharm) (Hons)

    2016-01-01

    Medication adherence is a crucial component in the treatment of chronic diseases. In the elderly, clinicians are faced with a unique set of problems associated with adherence that they may not have been adequately trained for. In this paper, we demonstrate the importance of medication adherence in the elderly through a case study. The different factors affecting medication adherence in the elderly are highlighted: patient, medication, health care providers, health care system, and socioeconom...

  20. Influence of human cytomegalvirus on the expression of natural-killer group 2-members receptors on the natural killer cells

    顾绍庆

    2014-01-01

    Objective To examine the effect of human cytomegalovirus(CMV)on the expressions of natural-killer group2-members(NKG2),including natural-killer group 2-member A(NKG2A),natural-killer group 2-member C(NKG2C)and natural-killer group 2-member D(NKG2D)receptors on the natural killer(NK)cells.Methods NK cells were isolated from the peripheral blood mononuclear cells of 20 healthy individuals using

  1. Killer plasma ready to devour the Earth

    Uhlig, R; Highfield, R

    2001-01-01

    A chance fluctuation of the 'vacuum universe' could disintegrate all atoms, according to CERN associate, Dr Allanach. Alternatively, so-called killer strangelets could "eat up the universe from the inside out". Should either of these scenarios occur, the most likely starting point is the Relativistic Heavy Ion Collider in Long Island, New York state (1 page).

  2. Positive selection on the killer whale mitogenome

    Foote, Andrew David; Morin, Phillip A; Durban, John W;

    2011-01-01

    Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches...

  3. Patient adherence with COPD therapy

    C. S. Rand

    2005-12-01

    Full Text Available Although there are very few published studies on adherence to treatment regimens in chronic obstructive pulmonary disease (COPD, the evidence that exists suggests that, as with asthma therapy, adherence is poor. Patient beliefs about COPD, as well as their motivation and expectations about the likelihood of success of medical interventions, can influence adherence rates. Other critical factors include the patient's understanding of their illness and therapy, and the complexity of the prescribed treatment regimen. Incorrect inhaler technique is also a common failing. When prescribing in primary or specialist care, healthcare professionals should address adherence as a vital part of the patient consultation. Improved patient education may also increase adherence rates.

  4. 'Killer' character of yeasts isolated from ethanolic fermentations

    Ceccato-Antonini Sandra Regina

    1999-01-01

    Full Text Available The number of killer, neutral and sensitive yeasts was determined from strains isolated from substrates related to alcoholic fermentations. From 113 isolates, 24 showed killer activity against NCYC 1006 (standard sensitive strain, while 30 were sensitive to NCYC 738 (standard killer strain, and 59 had no reaction in assays at 25-27°C. Two wild yeast strains of Saccharomyces cerevisiae and one of Candida colliculosa were tested against 10 standard killer strains and one standard sensitive strain in a cell x cell and well-test assays at four different pHs. None of the isolates displayed strong killer activity or were sensitive to the standard strains. All belonged to the neutral type. It was concluded that although the number of killer strains was high, this character cannot be used to protect ethanol fermentation processes against yeast contaminants like those which form cell clusters.

  5. Stochastic modeling of a serial killer

    Simkin, M V

    2012-01-01

    We analyze the time pattern of the activity of a serial killer, who during twelve years had murdered 53 people. The plot of the cumulative number of murders as a function of time is of "Devil's staircase" type. The distribution of the intervals between murders (step length) follows a power law with the exponent of 1.4. We propose a model according to which the serial killer commits murders when neuronal excitation in his brain exceeds certain threshold. We model this neural activity as a branching process, which in turn is approximated by a random walk. As the distribution of the random walk return times is a power law with the exponent 1.5, the distribution of the inter-murder intervals is thus explained. We confirm analytical results by numerical simulation.

  6. Improving adherence to antiretroviral therapy

    Nischal K; Khopkar Uday; Saple D

    2005-01-01

    Antiretroviral therapy (ART) has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in dise...

  7. Antihypertension medication adherence and associated factors at Dessie Hospital, North East Ethiopia, Ethiopia

    Legese Chelkeba

    2013-06-01

    Full Text Available Hypertension is an overwhelming global challenge. Despite the development of many effective anti hypertensive drugs, target to reduce morbidity and mortality due to high blood pressures are reached in only a minor of patients in clinical practice. Poor adherence is one of the biggest obstacles in therapeutic control of blood pressures. There are complaints from patients and physicians that the poor result of actual antihypertensive drug therapies. Many people with age indifference are attacked by this “silent killer” or which results in target organ damage as a complication. The aim of this study was to assess the magnitude of adherence and the factors associated with non-adherence to anti-hypertensive medication. Cross sectional exclusively convenient study was conducted by using structured questionnaires consisting of open and closed-ended questions on patients diagnosed for hypertension and have already been on anti hypertensive medications at least for three months at Dessie Referral hospital from 20/01/2012 to 29/01/2012. A total of hundred hypertensive patients were screened from hundred six cases by the exclusive criteria and the overall incidence of anti-hypertensive medication non adherence was 26%. The study identifies reasons why patients don’t adherent with the drug regiments. Among Factors associated with non adherence were health system and health care provider poor interaction with patient and therapy factors like frustration and unwanted effect of the medication in the long run. There was indication of non adherence from the study area. Great emphasis should be placed on intervention strategies such as patient counseling and increasing awareness of the physicians, all other prescribers and health care providers at large about the non adherence of anti hypertensive drugs as well as the complication what comes due to this medication non adherence. [Int J Res Med Sci 2013; 1(3.000: 191-197

  8. Suppression of natural killer cell activity by surgical stress in cancer patients and the underlying mechanisms.

    Yoshihara,Hisashi

    1986-04-01

    Full Text Available The influence of surgical stress on the natural killer (NK activity of peripheral blood lymphocytes in patients with carcinoma of the lung or gastrointestinal system was studied. The peripheral blood lymphocytes of the patients showed a marked decrease in NK activity against K-562 cells as target cells 1-2 days after surgery. The activity remained lowered for 2 weeks after thoractomy and for 1 week after laparotomy. No appreciable suppression of NK activity was observed with normal human peripheral blood lymphocytes preincubated with postoperative patient sera. Peripheral blood mononuclear cells obtained postoperatively from patients lost NK activity after ultraviolet irradiation, without any detectable loss of viability. Such irradiated mononuclear cells showed inhibition of NK activity after a 24-hour preincubation with peripheral blood lymphocytes from normal subjects. Similar suppressive activity was demonstrable in a fraction of mononuclear cells with adhesiveness to plastic petri dishes, while non-adherent cells had no such activity. When added immediately to the cytotoxicity assay system without the 24-hour preincubation, patient mononuclear cells caused no inhibition of NK activity, whereas adherent cells from normal subjects enhanced NK activity. The findings seems to indicate that, following surgical stress, plastic dish-adherent peripheral blood mononuclear cells become deprived of NK helper activity and exert suppression, thus causing postoperative depression of NK activity.

  9. Metabolic imaging of the tumor treated by KillerRed fluorescent protein-based photodynamic therapy in mice

    Sha, Shuang; Qin, Lingsong; Wang, Anle; Liu, Zheng; Yang, Fei; Jin, Honglin; Zhang, Zhihong

    2014-02-01

    KillerRed is a unique red fluorescent protein exhibiting excellent phototoxic properties. It has the ability to produce reactive oxygen species (ROS), for killing tumor cells in vitro upon laser irradiation and has the potential to act as a photosensitizer in the application of tumor therapy. Here, we investigated the effects of KillerRed-based photodynamic therapy (PDT) on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of pyridine nucleotide (PN) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed that the tumor was scabbed in response to 561 nm laser irradiation at 80 mV for 3 min, and the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. More importantly, a home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The flavoprotein was remarkable elevated and the PN was seldom increased with concomitant photobleaching of KillerRed fluorescence after irradiation, suggesting that flavoprotein and PN were oxidized in the course of KillerRed-based PDT.

  10. [Adherence to psychopharmacological treatment: Psychotherapeutic strategies to enhance adherence].

    Lencer, R; Korn, D

    2015-05-01

    Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50%. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. PMID:25903501

  11. Improved adherence with contingency management.

    Rosen, Marc I; Dieckhaus, Kevin; McMahon, Thomas J; Valdes, Barbara; Petry, Nancy M; Cramer, Joyce; Rounsaville, Bruce

    2007-01-01

    Contingency management (CM) based interventions that reinforce adherence to prescribed medications have shown promise in a variety of disadvantaged populations. Fifty-six participants with histories of illicit substance use who were prescribed antiretroviral medication but evidenced suboptimal adherence during a baseline assessment were randomly assigned to 16 weeks of weekly CM-based counseling or supportive counseling, followed by 16 additional weeks of data collection and adherence feedback to providers. The CM intervention involved review of data generated by electronic pill-bottle caps that record bottle opening (MEMS) and brief substance abuse counseling. CM participants were reinforced for MEMS-measured adherence with drawings from a bowl for prizes and bonus drawings for consecutive weeks of perfect adherence. Potential total earnings averaged $800. Mean MEMS-measured adherence to the reinforced medication increased from 61% at baseline to 76% during the 16-week treatment phase and was significantly increased relative to the supportive counseling group (p = 0.01). Furthermore, mean log-transformed viral load was significantly lower in the CM group. However, by the end of the 16-week follow-up phase, differences between groups in adherence and viral load were no longer significantly different. Proportions of positive urine toxicology tests did not differ significantly between the two groups at any phase. A brief CM-based intervention was associated with significantly higher adherence and lower viral loads. Future studies should evaluate methods to extend effects for longer term benefits. PMID:17263651

  12. 75 FR 2853 - False Killer Whale Take Reduction Team Meeting

    2010-01-19

    ... under the ESA is warranted (75 FR 316, January 5, 2010). Based on the overlap between the Insular and... National Oceanic and Atmospheric Administration RIN 0648-XT76 False Killer Whale Take Reduction Team... (NOAA), Department of Commerce. ACTION: Notice of establishment of a False Killer Whale Take...

  13. Pichia acaciae Killer System: Genetic Analysis of Toxin Immunity▿

    Paluszynski, John P.; Klassen, Roland; Meinhardt, Friedhelm

    2007-01-01

    The gene responsible for self-protection in the Pichia acaciae killer plasmid system was identified by heterologous expression in Saccharomyces cerevisiae. Resistance profiling and conditional toxin/immunity coexpression analysis revealed dose-independent protection by pPac1-2 ORF4 and intracellular interference with toxin function, suggesting toxin reinternalization in immune killer cells.

  14. Viral Evasion of Natural Killer Cell Activation

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-01-01

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections. PMID:27077876

  15. Adherence and Readiness to Antiretroviral Treatment

    Södergård, Björn

    2006-01-01

    Antiretroviral therapy places extraordinarily high demands on adherence, since non-adherence affects both individuals and society due to the spread of resistant viral strains. The aims of the thesis were to investigate the prevalence of adherence in Swedish HIV-infected patients, changes in adherence over time, and factors associated with adherence, including patients’ readiness to adhere. Further, to investigate the collaboration between nurses, doctors and pharmacists after the introduction...

  16. The influence of Pichia killer toxins on the wine spoilage yeasts

    Urszula Błaszczyk; Pawel Satora; Pawel Sroka

    2015-01-01

    Killer yeasts are able to produce toxins that antagonize the growth of susceptible yeasts cells of the same species or the ones that are related to them. Killer strains are resistant to their own toxins but can be sensitive to killer proteins of other yeasts. The killer proteins of Pichia spp. are known for its broad spectrum of antifungal activity including pathogens such as Candida albicans. The aim of the study was to investigate the potential of the partly purified killer toxi...

  17. Occurrence of Killer Yeast Strains in Fruit and Berry Wine Yeast Populations

    Gulbiniene, Gintare; Kondratiene, Laima; Jokantaite, Tautvile; Serviene, Elena; Melvydas, Vytautas; Petkuniene, Giedre

    2004-01-01

    Apple, cranberry, chokeberry and Lithuanian red grape wine yeast populations were used for the determination of killer yeast occurrence. According to the tests of the killer characteristics and immunity the isolated strains were divided into seven groups. In this work the activity of killer toxins purified from some typical strains was evaluated. The analysed strains produced different amounts of active killer toxin and some of them possessed new industrially significant killer properties. To...

  18. Ecotypic variation and predatory behavior among killer whales (Orcinus orca) off the eastern Aleutian Islands, Alaska

    Matkin, Craig O.; Barrett-Lennard, Lance G.; Yurk, Harald; Ellifrit, David; Andrew W Trites

    2007-01-01

    From 2001 to 2004 in the eastern Aleutian Islands, Alaska, killer whales (Orcinus orca) were encountered 250 times during 421 days of surveys that covered a total of 22,491 miles. Three killer whale groups (resident, transient, and offshore) were identified acoustically and genetically. Resident killer whales were found 12 times more frequently than transient killer whales, and offshore killer whales were encountered only once. A minimum of 901 photographically identified resident wh...

  19. Improving adherence to antiretroviral therapy

    Nischal K

    2005-01-01

    Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

  20. From Pichia anomala killer toxin through killer antibodies to killer peptides for a comprehensive anti-infective strategy.

    Polonelli, Luciano; Magliani, Walter; Ciociola, Tecla; Giovati, Laura; Conti, Stefania

    2011-01-01

    "Antibiobodies", antibodies (Abs) with antibiotic activity, internal image of a Pichia anomala killer toxin (PaKT) characterized by microbicidal activity against microorganisms expressing β-glucans cell-wall receptors (PaKTRs), were produced by idiotypic vaccination with a PaKT-neutralizing monoclonal Ab (PaKT-like Abs) or induced by a protein-conjugated β-glucan. Human natural PaKT-like Abs (PaKTAbs) were found in the vaginal fluid of women infected with KT-sensitive microorganisms. Monoclonal and recombinant PaKT-like Abs, and PaKTAbs proved to be protective against experimental candidiasis, cryptococcosis and aspergillosis. A killer decapeptide (KP), synthesized from the sequence of a recombinant PaKT-like Ab or produced in transgenic plants, showed a microbicidal activity in vitro, neutralized by β-glucans, a therapeutic effect in vivo, against experimental mucosal and systemic mycoses, and a prophylactic role in planta, against phytopathogenic microorganisms, respectively. KP showed fungicidal properties against all the defective mutants of a Saccharomyces cerevisiae library, inclusive of strains recognized to be resistant to conventional antifungal drugs. KP inhibited in vitro, ex vivo and/or in vivo HIV-1 and Influenza A virus replication, owing to down-regulation of CCR5 co-receptors, physical block of the gp120-receptor interaction and reduction in the synthesis of glycoproteins, HA and M1 in particular. KP modulated the expression of costimulatory and MHC molecules on murine dendritic cells, improving their capacity to induce lymphocyte proliferation. KP, proven to be devoid of cytotoxicity on human cells, showed self-assembly-releasing hydrogel-like properties, catalyzed by β 1,3 glucan. PaKT's biotechnological derivatives may represent the prototypes of novel antifungal vaccines and anti-infective drugs characterized by different mechanisms of action. PMID:20714805

  1. Positive selection on the killer whale mitogenome.

    Foote, Andrew D; Morin, Phillip A; Durban, John W; Pitman, Robert L; Wade, Paul; Willerslev, Eske; Gilbert, M Thomas P; da Fonseca, Rute R

    2011-02-23

    Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches. It is therefore a suitable organism for testing this hypothesis. We compared a global dataset of the complete mitochondrial genomes of 139 individuals for amino acid changes that were associated with radical physico-chemical property changes and were influenced by positive selection. Two such selected non-synonymous amino acid changes were found; one in each of two ecotypes that inhabit the Antarctic pack ice. Both substitutions were associated with changes in local polarity, increased steric constraints and α-helical tendencies that could influence overall metabolic performance, suggesting a functional change. PMID:20810427

  2. Antiproton cell experiment: antimatter is a better killer

    2006-01-01

    "European Organization for Nuclear Research is reporting that results from a three year study of antiprotons for neoplasm irrdiation showed a better cellular killer with a smaller lethal dose." (1,5 page)

  3. Gulf of Mexico killer whale photo-ID catalog

    National Oceanic and Atmospheric Administration, Department of Commerce — Photo-identification data on killer whales occupying the northern Gulf of Mexico have been collected in association with large vessel surveys since 1991....

  4. Final Critical Habitat for Southern Resident Killer Whales

    US Fish and Wildlife Service, Department of the Interior — A geospatial data set depicting the boundaries of marine areas designated as critical habitat under the Endangered Species Act (ESA) for Southern Resident killer...

  5. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model

    Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena

    2015-01-01

    The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation. PMID:26657001

  6. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    Marina Shirmanova

    Full Text Available The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm and pulsed laser (584 nm, 10 Hz, 18 ns modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

  7. The challenge of patient adherence.

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin

    2005-09-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  8. Inhibition of bacteria contaminating alcoholic fermentations by killer yeasts

    Maria Cristina Meneghin; Vanda Renata Reis; Sandra Regina Ceccato-Antonini

    2010-01-01

    The aim of this work was to study the in vitro antibacterial activity possessed by killer yeast strains against bacteria contaminating alcoholic fermentation (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides), in cell X cell and cell X crude toxin preparations. The bacteria were not inhibited by any S. cerevisiae killer strains (5 out of 11). The inhibition caused by two crude toxin preparations (Trichosporon figueirae and Candida sp) against L...

  9. Production and characterization of yeast killer toxin monoclonal antibodies

    Polonelli, L; Morace, G

    1987-01-01

    Monoclonal antibodies were obtained after fusion of mouse myeloma cells with spleen cells isolated from mice primed with a crude extract of yeast killer toxin produced by a strain of Hansenula anomala. Hybridomas were selected by specific immunoassay reaction of their fluid with crude yeast killer toxin extract. Among the monoclonal antibodies, which were characterized by the Western blot technique, one (designated KT4) proved to have precipitating properties, thus permitting the neutralizati...

  10. Evolution of male-killer suppression in a natural population.

    Emily A Hornett

    2006-09-01

    Full Text Available Male-killing bacteria are widespread in arthropods, and can profoundly alter the reproductive biology of their host species. Here we detail the first case of complete suppression of a male killer. The nymphalid butterfly Hypolimnas bolina is infected with a strain of the bacterium Wolbachia, wBol1, which kills male host embryos in Polynesian populations, but does not do so in many areas of Southeast Asia, where both males and female adults are naturally infected, and wBol1-infected females produce a 1:1 sex ratio. We demonstrate that absence of male killing by wBol1 is associated with dominant zygotic suppression of the action of the male killer. Simulations demonstrate host suppressors of male-killer action can spread very rapidly, and historical data indicating the presence of male killing in Southeast Asia in the very recent past suggests suppressor spread has been a very recent occurrence. Thus, male killer/host interactions are much more dynamic than previously recognised, with rapid and dramatic loss of the phenotype. Our results also indicate that suppression can render male killers completely quiescent, leading to the conclusion that some species that do not currently express a male killer may have done so in the past, and thus that more species have had their biology affected by these parasites than previously believed.

  11. Transient killer whale range - Satellite tagging of West Coast transient killer whales to determine range and movement patterns

    National Oceanic and Atmospheric Administration, Department of Commerce — Transient killers whales inhabit the West Coast of the United States. Their range and movement patterns are difficult to ascertain, but are vital to understanding...

  12. In vitro augmentation of natural killer cell activity by manganese chloride

    The in vitro cultivation of murine spleen cells with MnCl2 resulted in the enhancement of natural killer (NK) cell activity as measured in a 4-h 51Cr-release assay. Optimal enhancement of NK activity was observed at concentrations of 10-20 μg MnCl2/culture (72-144 μM Mn2+). Enhancement of NK activity by MnCl2 was not associated with any changes in the number or viability of cells following culture. The addition of antiasialo GM1 antibody and complement to spleen cell cultures completely abrogated the enhancement of NK activity by MnCl2. The enhancement of NK activity by MnCl2 in vitro was accompanied by interferon induction. The addition of rabbit antimouse interferon to spleen cells cultured with MnCl2 reduced NK activity. NK activity in cultures treated with MnCl2 was also reduced upon removal of plastic adherent cells. However, restoration of enhanced NK activity by addition of adherent cells to nonadherent cells in the presence of MnCl2 was not observed. Similar effects of NK activity were observed with polyinosinic-polycytidylic acid (Poly I x C), a known interferon inducer and NK enhancer. The results demonstrate that murine splenic NK activity is enhanced in vitro by MnCl2 and that this enhancement may be mediated by interferon induction. The results also suggest that in vitro enhancement of NK activity by MnCl2, as with Poly I x C, may require participation of an adherent cell population for NK augmentation

  13. Positioning Effects of KillerRed inside of Cells correlate with DNA Strand Breaks after Activation with Visible Light

    Waldeck, Waldemar; Mueller, Gabriele; Wiessler, Manfred; Tóth, Katalin; Braun, Klaus

    2011-01-01

    Fluorescent proteins (FPs) are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED), used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS) resulting in photokilling processes. It is a given that the extent of...

  14. Adherence with Preventive Medication in Childhood Asthma

    Scott Burgess

    2011-01-01

    Full Text Available Suboptimal adherence with preventive medication is common and often unrecognised as a cause of poor asthma control. A number of risk factors for nonadherence have emerged from well-conducted studies. Unfortunately, patient report a physician's estimation of adherence and knowledge of these risk factors may not assist in determining whether non-adherence is a significant factor. Electronic monitoring devices are likely to be more frequently used to remind patients to take medication, as a strategy to motivate patients to maintain adherence, and a tool to evaluate adherence in subjects with poor disease control. The aim of this paper is to review non-adherence with preventive medication in childhood asthma, its impact on asthma control, methods of evaluating non-adherence, risk factors for suboptimal adherence, and strategies to enhance adherence.

  15. UV-killed protoplast fusion as a method for breeding killer yeasts

    A simple method for breeding killer yeasts without changing the nuclear genotype was described. Killer plasmids were introduced into recipient cells just after killing the protoplasts carrying killer plasmids with UV-rays. For the donors, UV-sensitive strains harboring killer plasmids having 100 base pair deletion and drug resistant mitochondria were constructed. Almost all fusants obtained showed the same nuclear phenotype as the recipient but had killer activity and drug resistance. Killer sake yeast were bred using a commercial strain, Kyokai 7,as the recipient, and they were confirmend to produce sake of the same quality as that produced with strain Kyokai 7 with no contamination by wild yeast

  16. Drug resistance in rat colon cancer cell lines is associated with minor changes in susceptibility to cytotoxic cells

    W. van de Vrie (Wim); S.A.M. van der Heyden (Sylke); E.E.O. Gheuens (Eric); H.H. Bijma (Hilmar); E.A. de Bruijn (Ernst); R.L. Marquet (Richard); A.T. van Oosterom (Allan); A.M.M. Eggermont (Alexander)

    1993-01-01

    textabstractThe development of resistance to anticancer drugs urges the search for different treatment modalities. Several investigators have reported the concomitant development of drug resistance and resistance to natural killer (NK), lymphokine-activated killer (LAK) or monocyte/macrophage cell l

  17. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...

  18. Inhibition of bacteria contaminating alcoholic fermentations by killer yeasts

    Maria Cristina Meneghin

    2010-10-01

    Full Text Available The aim of this work was to study the in vitro antibacterial activity possessed by killer yeast strains against bacteria contaminating alcoholic fermentation (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides, in cell X cell and cell X crude toxin preparations. The bacteria were not inhibited by any S. cerevisiae killer strains (5 out of 11. The inhibition caused by two crude toxin preparations (Trichosporon figueirae and Candida sp against L. plantarum was surprisingly high but not in the same extent for B. subtilis, especially with three killer strains (Candida glabrata, Pichia anomala and Candida sp. L. mesenteroides and L. fermentum strains were neither inhibited in cell X cell nor crude toxin X cell tests. The results suggested that killer activity of yeasts might operate over bacteria and it could be used for the biocontrol of contaminating bacteria from alcoholic fermentation if additional tests on toxin application in fermentation shown to be successful. A wider panel of S. cerevisiae killer strains should be used to confirm that they were really unable to control the growth of these Gram-positive bacteria.Este estudo mostrou a atividade antibacteriana in vitro de linhagens de leveduras killer contra bactérias contaminantes da fermentação alcoólica (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides, em testes célula X célula e célula X toxina bruta. As bactérias não foram inibidas por linhagens killer de Saccharomyces cerevisiae (5 dentre 11. Os preparados brutos de toxina de duas leveduras (Trichosporon figueirae e Candida sp causaram uma alta inibição no crescimento de L. plantarum, mas não na mesma extensão para B. subtilis, especialmente para três leveduras killer (Candida glabrata, Pichia anomala e Candida sp. Linhagens de L. mesenteroides e L. fermentum não foram inibidas em nenhum dos testes. Os resultados obtidos neste

  19. KillerRed and miniSOG as genetically encoded photosensitizers for photodynamic therapy of cancer

    Shirmanova, Marina V.; Serebrovskaya, Ekaterina O.; Snopova, Ludmila B.; Kuznetsova, Maria M.; Ryumina, Alina P.; Turchin, Ilya V.; Sergeeva, Ekaterina A.; Ignatova, Nadezhda I.; Klementieva, Natalia V.; Lukyanov, Konstantin A.; Lukyanov, Sergey A.; Zagaynova, Elena V.

    2013-06-01

    Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.

  20. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

    Gianfranco ePittari

    2015-05-01

    Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  1. Transtornos de personalidade, psicopatia e serial killers Personality disorders, psychopathy and serial killers

    Hilda C P Morana

    2006-10-01

    Full Text Available OBJETIVO: Apresentar as características básicas dos diversos transtornos específicos de personalidade, mas centrando-se no transtorno de personalidade anti-social, fazendo sua diferenciação com psicopatia. O estudo ainda se propõe a abordar a figura do serial killer, apontando a presença de aspectos psicopáticos no homicídio seriado. MÉTODO: Uma revisão bibliográfica foi feita no sentido de se abordar convergências e divergências entre diversos autores sobre um assunto tão polêmico, sobretudo quanto à viabilidade de tratamento dessa clientela forense. RESULTADOS: Enquanto o transtorno de personalidade anti-social é um diagnóstico médico, pode-se entender o termo "psicopatia", pertencente à esfera psiquiátrico-forense, como um "diagnóstico legal". Não se pode falar ainda de tratamento eficaz para os chamados "serial killers". CONCLUSÃO: Os transtornos de personalidade, especialmente o tipo anti-social, representam ainda hoje um verdadeiro desafio para a psiquiatria forense. O local mais adequado e justo para seus portadores, bem como recomendação homogênea e padronizada de tratamento são questões ainda não respondidas.OBJECTIVE: To illustrate the basic characteristics of several specific personality disorders, focusing mainly in antisocial personality disorder. The differences between antisocial personality disorder and psychopathy are highlighted. Serial killers and its psychopathic aspects are also discussed. METHOD: A bibliographic review was completed in order to outline convergences and divergences among different authors about this controversial issue, especially those concerning the possibility of treatment. RESULTS: While anti-social personality disorder is a medical diagnosis, the term "psychopathy" (which belongs to the sphere of forensic psychiatry may be understood as a "legal diagnosis". It is not still possible to identify an effective treatment for serial killers. CONCLUSION: Personality disorders

  2. Transtornos de personalidade, psicopatia e serial killers Personality disorders, psychopathy and serial killers

    Hilda C P Morana; Stone, Michael H.; Elias Abdalla-Filho

    2006-01-01

    OBJETIVO: Apresentar as características básicas dos diversos transtornos específicos de personalidade, mas centrando-se no transtorno de personalidade anti-social, fazendo sua diferenciação com psicopatia. O estudo ainda se propõe a abordar a figura do serial killer, apontando a presença de aspectos psicopáticos no homicídio seriado. MÉTODO: Uma revisão bibliográfica foi feita no sentido de se abordar convergências e divergências entre diversos autores sobre um assunto tão polêmico, sobretudo...

  3. Models for Natural Killer Cell Repertoire Formation

    Ramit Mehr

    2003-01-01

    Full Text Available Natural killer (NK cells lyse only cells that do not express sufficient levels of self class I MHC molecules. Inhibition of lysis is mediated by inhibitory receptors expressed by NK cells, such as the murine Ly49 receptors, that bind to MHC class I molecules. Since inhibitory receptor genes and MHC class I genes are located on different chromosomes, and are hence not automatically co-inherited, NK cells apparently adapt to the MHC environment during their development. Two models have been proposed to account for this “education” process of NK cells. The two-step selection model postulates that developing NK cells initiate the stable expression of a random set of Ly49 genes, and then undergo two selection steps, one for cells that express a sufficient number of self-MHC receptors, and one against cells that express too many inhibitory receptors. The sequential model postulates that a cell keeps initiating the stable expression of additional inhibitory receptors until a sufficient expression level of self-MHC specific receptors is reached, and the cell matures. In this study we implement both models in computer simulations, and compare simulation results to experimental data, in order to evaluate the relative plausibility of the two models.

  4. Natural Killer cells and liver fibrosis

    Frank eFasbender

    2016-01-01

    Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

  5. SRKW seasonal occurence - Patterns of seasonal occurrence of Southern Resident Killer Whales

    National Oceanic and Atmospheric Administration, Department of Commerce — Patterns of seasonal occurrence of Southern Resident Killer Whales (SRKW) throughout their range. Southern Resident Killer Whales are listed as a Distinct...

  6. Introducing the Adherence Strategy Engineering Framework (ASEF)

    Wagner, Stefan Rahr; Toftegaard, Thomas Skjødeberg; Bertelsen, Olav W.

    2013-01-01

    resulting in reduced data quality and suboptimal treatment. Objectives: The aim of this paper is to introduce the Adherence Strategy Engineering Framework (ASEF) as a method for developing novel technology-based adherence strategies to assess and improve patient adherence levels in the unsupervised setting...

  7. Enhancing Adherence in Clinical Exercise Trials.

    O'Neal, Heather A.; Blair, Steven N.

    2001-01-01

    Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…

  8. 50 CFR 226.206 - Critical habitat for the Southern Resident killer whale (Orcinus orca).

    2010-10-01

    ... killer whale (Orcinus orca). 226.206 Section 226.206 Wildlife and Fisheries NATIONAL MARINE FISHERIES... CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section. The...

  9. File list: ALL.Bld.10.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  13. File list: DNS.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available DNS.Bld.50.AllAg.Natural_Killer_Cells mm9 DNase-seq Blood Natural Killer Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.Natural_Killer_Cells.bed ...

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  20. File list: Pol.Bld.05.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  1. File list: ALL.Bld.05.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available ALL.Bld.05.AllAg.Natural_Killer_Cells mm9 All antigens Blood Natural Killer Cells S...48,SRX485450 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Natural_Killer_Cells.bed ...

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  3. File list: DNS.Bld.20.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  4. File list: ALL.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  5. File list: Unc.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  6. File list: Pol.Bld.20.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  7. File list: DNS.Bld.10.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  8. File list: Unc.Bld.05.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  9. File list: Pol.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  10. File list: His.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available His.Bld.50.AllAg.Natural_Killer_Cells mm9 Histone Blood Natural Killer Cells SRX485...58404,SRX658418,SRX658388,SRX338033 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Natural_Killer_Cells.bed ...

  11. Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes

    Hejazi, Maryam; Manser, Angela R.; Fröbel, Julia; Kündgen, Andrea; Zhao, Xiaoyi; Schönberg, Kathrin; Germing, Ulrich; Haas, Rainer; Gattermann, Norbert; Uhrberg, Markus

    2015-01-01

    Natural killer cells are well known to mediate anti-leukemic responses in myeloid leukemia but their role in myelodysplastic syndromes is not well understood. Here, in a cohort of newly diagnosed patients (n=75), widespread structural and functional natural killer cell defects were identified. One subgroup of patients (13%) had a selective deficiency of peripheral natural killer cells (count

  12. How can we improve adherence?

    Price, Patricia

    2016-01-01

    Many patients with wound healing difficulties are also coping with the management of a chronic disease or chronic condition that requires them to make lifestyle behaviour changes, for example, managing glucose levels through diet and exercise and regular foot inspection. Many find it difficult to make such changes and often experience feelings of powerlessness when faced with a lifetime of behavioural and psychological change. This article will explore the importance of understanding the patient difficulties associated with adherence to a regime and how life changes can be difficult to maintain over sustained periods of time. However, the article will also discuss the importance of this topic in trying to understand the clinical evidence base for treatment--as many clinical trials investigating treatments for the diabetic foot do not include information on the extent to which patients in the trial conformed to the trial protocol. The article gives an overview of recent developments--including lessons we can learn from other chronic conditions where permanent life changes are required--in particular the need to keep health messages simple, tailored to the individual and repeated frequently. The evidence to date suggests that no one single form of adherence intervention will work with all patients; this is not surprising given complex and multifactorial nature of adherence and the myriad of barriers that exist that patients and health care professionals need to overcome. PMID:26453542

  13. Adherence and health care costs

    Iuga AO

    2014-02-01

    Full Text Available Aurel O Iuga,1,2 Maura J McGuire3,4 1Johns Hopkins Bloomberg School of Public Health, 2Johns Hopkins University, 3Johns Hopkins Community Physicians, 4Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Medication nonadherence is an important public health consideration, affecting health outcomes and overall health care costs. This review considers the most recent developments in adherence research with a focus on the impact of medication adherence on health care costs in the US health system. We describe the magnitude of the nonadherence problem and related costs, with an extensive discussion of the mechanisms underlying the impact of nonadherence on costs. Specifically, we summarize the impact of nonadherence on health care costs in several chronic diseases, such as diabetes and asthma. A brief analysis of existing research study designs, along with suggestions for future research focus, is provided. Finally, given the ongoing changes in the US health care system, we also address some of the most relevant and current trends in health care, including pharmacist-led medication therapy management and electronic (e-prescribing. Keywords: patient, medication, adherence, compliance, nonadherence, noncompliance, cost

  14. Transplantation and innate immunity: the lesson of natural killer cells

    Moretta Lorenzo

    2009-12-01

    Full Text Available Abstract Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor. In particular, donor-derived natural killer cells, which are alloreactive (i.e. KIR/HLA mismatched towards recipient cells, significantly contribute to the eradication of leukemia blasts escaping the preparative regimen to transplantation. A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months. This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.

  15. Adherence and quality of care in IBD

    Bager, Palle; Julsgaard, Mette; Vestergaard, Thea;

    2016-01-01

    different aspects of adherence and to identify predictors of non-adherence, including the quality of care, for outpatients with IBD. MATERIALS AND METHODS: An anonymous electronic questionnaire was used to investigate different aspects of adherence, the quality of care, patient involvement and shared...... decision making among 377 IBD outpatients. RESULTS: Three hundred (80%) filled in the questionnaire. The overall adherence rate was 93%. Young age (< 35 years old) and smoking were significantly associated with non-adherence (prevalence odds ratio (POR) 2.98, 95% CI 1.04-8.52, p < 0.05 and POR 3.88, 95% CI...

  16. Natural killer cell activity during premedication, anaesthesia and surgery

    Tønnesen, E; Mickley, H; Grunnet, N

    1983-01-01

    Natural killer (NK) cell activity of peripheral blood mononuclear cells was measured against K-562 target cells in a 51Cr release assay in eight patients undergoing total hip replacement surgery. Eight consecutive blood samples were taken from each patient. A significant increase of NK cell...... days. The findings of this study indicate that premedication, anaesthesia and surgery cause a rapid and transient increase in NK cell activity, followed by a decline in activity postoperatively. The transient increase in activity may be explained by mobilization of natural killer cells from extravasal...

  17. Adaptive prolonged postreproductive life span in killer whales.

    Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

    2012-09-14

    Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals. PMID:22984064

  18. Asthma and Adherence to Inhaled Corticosteroids

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli

    2015-01-01

    Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means to...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, < 12 y of formal education, and poor communication with the health-care provider, whereas improved adherence was associated with...... asthma-related hospitalizations could be attributed to poor adherence. Most studies have reported an increase in adherence following focused interventions, followed by an improvement in quality of life, symptoms, FEV1, and oral corticosteroid use. However, 2 studies found no difference in health...

  19. Adherence to Methotrexate therapy in Rheumatoid Arthritis

    Arshad, Nasim; Ahmad, Nighat Mir; Saeed, Muhammad Ahmed; Khan, Saira; Batool, Shabnam; Farman, Sumaira

    2016-01-01

    Objective: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. Methods: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. Result: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. Conclusion: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group.

  20. Ultrasonic whistles of killer whales (Orcinus orca) recorded in the North Pacific (L).

    Filatova, Olga A; Ford, John K B; Matkin, Craig O; Barrett-Lennard, Lance G; Burdin, Alexander M; Hoyt, Erich

    2012-12-01

    Ultrasonic whistles were previously found in North Atlantic killer whales and were suggested to occur in eastern North Pacific killer whales based on the data from autonomous recorders. In this study ultrasonic whistles were found in the recordings from two encounters with the eastern North Pacific offshore ecotype killer whales and one encounter with the western North Pacific killer whales of unknown ecotype. All ultrasonic whistles were highly stereotyped and all but two had downsweep contours. These results demonstrate that specific sound categories can be shared by killer whales from different ocean basins. PMID:23231094

  1. Effects of ultraviolet irradiation on natural killer cell function in systemic lupus erythematosus

    In vitro irradiation with long wavelength ultraviolet light (UV-A), in clinically relevant dosages, of a natural killer cell line containing cell preparations from 17 control subjects reduced natural killer cell cytotoxicity with the cell line K562 as target. The spontaneous function of natural killer cells from 12 patients with systematic lupus erythematosus (SLE) correlated inversely with the one hour erythrocyte sedimentation rate, but not with glucocorticoid doses. After UV-A exposure, natural killer cells from patients with SLE exert either increased or decreased cytotoxicity, and the direction of change is inversely correlated with the spontaneous natural killer cell function. (Author)

  2. Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes.

    Hejazi, Maryam; Manser, Angela R; Fröbel, Julia; Kündgen, Andrea; Zhao, Xiaoyi; Schönberg, Kathrin; Germing, Ulrich; Haas, Rainer; Gattermann, Norbert; Uhrberg, Markus

    2015-05-01

    Natural killer cells are well known to mediate anti-leukemic responses in myeloid leukemia but their role in myelodysplastic syndromes is not well understood. Here, in a cohort of newly diagnosed patients (n=75), widespread structural and functional natural killer cell defects were identified. One subgroup of patients (13%) had a selective deficiency of peripheral natural killer cells (count <10/mm(3) blood) with normal frequencies of T and natural killer-like T cells. Natural killer cell-deficient patients were predominantly found in high-risk subgroups and deficiency of these cells was significantly associated with poor prognosis. In the second subgroup, comprising the majority of patients (76%), natural killer cells were present but exhibited poor cytotoxicity. The defect was strongly associated with reduced levels of perforin and granzyme B. Notably, natural killer cell function and arming of cytotoxic granules could be fully reconstituted by in vitro stimulation. Further phenotypic analysis of these patients revealed an immature natural killer cell compartment that was biased towards CD56(bright) cells. The residual CD56(dim) cells exhibited a significant increase of the unlicensed NKG2A(-)KIR(-) subset and a striking reduction in complexity of the repertoire of killer cell immunoglobulin-like receptors. Taken together, these results suggest that the widespread defects in natural killer cell function occurring in patients with myelodysplastic syndromes are mostly due to either unsuccessful or inefficient generation of mature, functionally competent natural killer cells, which might contribute to disease progression through impaired immune surveillance. PMID:25682594

  3. Adherence of Pseudomonas aeruginosa to contact lenses

    The purpose of this research was to examined the interactions of P. aeruginosa with hydrogel contact lenses and other substrata, and characterize adherence to lenses under various physiological and physicochemical conditions. Isolates adhered to polystyrene, glass, and hydrogel lenses. With certain lens types, radiolabeled cells showed decreased adherence with increasing water content of the lenses, however, this correlation with not found for all lenses. Adherence to rigid gas permeable lenses was markedly greater than adherence to hydrogels. Best adherence occurred near pH 7 and at a sodium chloride concentration of 50 mM. Passive adhesion of heat-killed cells to hydrogels was lower than the adherence obtained of viable cells. Adherence to hydrogels was enhanced by mucin, lactoferrin, lysozyme, IgA, bovine serum albumin, and a mixture of these macromolecules. Adherence to coated and uncoated lenses was greater with a daily-wear hydrogel when compared with an extended-wear hydrogel of similar polymer composition. Greater adherence was attributed to a higher concentration of adsorbed macromolecules on the 45% water-content lens in comparison to the 55% water-content lens

  4. Proteomics of membrane microdomains from activated human natural killer cells

    Man, Petr; Pompach, Petr; Vančurová, Markéta; Novák, Petr; Kavan, Daniel; Mrázek, Hynek; Bezouška, Karel

    Bremen : German Society for Mass Spectrometry, 2009. s. 128-128. [International Mass Spectrometry Conference /18./. 30.08.2009-04.09.2009, Bremen] R&D Projects: GA MŠk LC07017; GA AV ČR KJB500200612 Institutional research plan: CEZ:AV0Z50200510 Keywords : mass spectrometry * natural killer cells Subject RIV: EE - Microbiology, Virology

  5. Defective Natural Killer cell antiviral capacity in paediatric HBV infection

    Heiberg, Ida Louise; Laura J., Pallett; Winther, Thilde Nordmann;

    2015-01-01

    Natural Killer (NK) cells exhibit dysregulated effector function in adult chronic HBV infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK...

  6. Depressed natural killer cell activity in acute myocardial infarction

    Klarlund, K; Pedersen, B K; Theander, T G;

    1987-01-01

    Natural killer (NK) cell activity against K562 target cells was measured in patients within 24 h of acute myocardial infarction (AMI) and regularly thereafter for 6 weeks. NK cell activity was suppressed on days 1, 3, and 7 (P less than 0.01), day 14 (P less than 0.05) and at 6 weeks (P = 0...

  7. Life history evolution: what does a menopausal killer whale do?

    Whitehead, Hal

    2015-03-16

    Menopause evolved in humans and whales, presumably because older females can help their kin. But how do they help? New research shows that post-menopausal female killer whales lead foraging groups. This leadership is most significant when food is scarce. PMID:25784039

  8. EFFECT OF NICKEL AND MANGANESE ON NATURAL KILLER CELL ACTIVITY

    A single intramuscular injection of NiCl2 causes a suppression of natural killer (NK) cell activity, while a single injection of MnCl2 enhances NK activity. When injected together Mn preempts the suppressive effect of Ni on NK activity.

  9. Measurement complexity of adherence to medication

    Galato D; Schuelter-Trevisol F; Piovezan AP

    2012-01-01

    Dayani Galato, Fabiana Schuelter-Trevisol, Anna Paula PiovezanMaster Program in Health Sciences, University of Southern Santa Catarina (Unisul) Tubarão, Santa Catarina, BrazilAdherence to pharmacologic therapy is a major challenge for the rational use of medicines, particularly when it comes to antiretroviral drugs that require adherence to at least 95% of prescribed doses.1 Studies in this area are always important and contribute to medication adherence understanding, even though ...

  10. Family interaction and treatment adherence after stroke.

    Evans, R L; Bishop, D S; Matlock, A L; Stranahan, S; Smith, G G; Halar, E M

    1987-08-01

    Caregivers of 60 stroke patients were assessed five months after patient discharge from a stroke care unit to determine the relationship between family function and poststroke treatment adherence. Areas of family interaction which were significantly related to ratings of treatment adherence included problem solving, communication, and affective involvement. Better functioning families were consistently high on signs of treatment adherence. Findings suggest that families with specific dysfunction may not be as capable of helping patients comply with rehabilitation efforts as families who function more effectively. Thorough family assessment to identify which areas of family interaction are most problematic in relation to adherence issues is recommended. PMID:3619615

  11. Plasmodium vivax adherence to placental glycosaminoglycans.

    Kesinee Chotivanich

    Full Text Available BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

  12. Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression.

    Guan, P; Bassiri, H; Patel, N P; Nichols, K E; Das, R

    2016-05-01

    Invariant natural killer T cells (iNKTs) are innate-like lipid-reactive T lymphocytes that express an invariant T-cell receptor (TCR). Following engagement of the iTCR, iNKTs rapidly secrete copious amounts of Th1 and Th2 cytokines and promote the functions of several immune cells including NK, T, B and dendritic cells. Accordingly, iNKTs bridge the innate and adaptive immune responses and modulate susceptibility to autoimmunity, infection, allergy and cancer. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective treatments for patients with hematologic malignancies. However, the beneficial graft versus leukemia (GvL) effect mediated by the conventional T cells contained within the allograft is often hampered by the concurrent occurrence of graft versus host disease (GvHD). Thus, developing strategies that can dissociate GvHD from GvL remain clinically challenging. Several preclinical and clinical studies demonstrate that iNKTs significantly attenuate GvHD without abrogating the GvL effect. Besides preserving the GvL activity of the donor graft, iNKTs themselves exert antitumor immune responses via direct and indirect mechanisms. Herein, we review the various mechanisms by which iNKTs provide antitumor immunity and discuss their roles in GvHD suppression. We also highlight the opportunities and obstacles in manipulating iNKTs for use in the cellular therapy of hematologic malignancies. PMID:26878658

  13. Adherence to vitamin supplementation following adolescent bariatric surgery

    Modi, Avani C.; Zeller, Meg H.; Xanthakos, Stavra A.; Jenkins, Todd M.; Inge, Thomas H.

    2013-01-01

    Adolescents with extreme obesity, who have undergone bariatric surgery, must adhere to many lifestyle and nutritional recommendations, including multivitamin therapy. Little is know about multivitamin adherence following adolescent bariatric surgery. The present study aims to document self-reported and electronically-monitored adherence to multivitamins, determine convergence between self-report and electronic monitoring adherence for multivitamins, and identify barriers to multivitamin adher...

  14. Predicting asthma exacerbations employing remotely monitored adherence.

    Killane, Isabelle; Sulaiman, Imran; MacHale, Elaine; Breathnach, Aoife; Taylor, Terence E; Holmes, Martin S; Reilly, Richard B; Costello, Richard W

    2016-03-01

    This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events. PMID:27222733

  15. Phylogenomics of the killer whale indicates ecotype divergence in sympatry.

    Moura, A E; Kenny, J G; Chaudhuri, R R; Hughes, M A; Reisinger, R R; de Bruyn, P J N; Dahlheim, M E; Hall, N; Hoelzel, A R

    2015-01-01

    For many highly mobile species, the marine environment presents few obvious barriers to gene flow. Even so, there is considerable diversity within and among species, referred to by some as the 'marine speciation paradox'. The recent and diverse radiation of delphinid cetaceans (dolphins) represents a good example of this. Delphinids are capable of extensive dispersion and yet many show fine-scale genetic differentiation among populations. Proposed mechanisms include the division and isolation of populations based on habitat dependence and resource specializations, and habitat release or changing dispersal corridors during glacial cycles. Here we use a phylogenomic approach to investigate the origin of differentiated sympatric populations of killer whales (Orcinus orca). Killer whales show strong specialization on prey choice in populations of stable matrifocal social groups (ecotypes), associated with genetic and phenotypic differentiation. Our data suggest evolution in sympatry among populations of resource specialists. PMID:25052415

  16. Uterine Natural Killer Cells: Their Choices, Their Missions

    Jianhong Zhang; B Anne Croy; Zhigang Tian

    2005-01-01

    Uterine natural killer (uNK) cells, sharing many characters with peripheral blood natural killer (pNK) cells, are a major uterine lymphocyte population at early gestational stages during normal pregnancy in placental mammals.The functions of uNK cells include cytokine production and cytotoxcity that are regulated by signals through activating and inhibitory receptors. UNK cells differ from pNK cells however and contribute to the structural changes that accompany the differentiation of the maternal-fetal interface. Immunological mechanisms must provide a balanced environment for uNK cell proliferation, differentiation and activation through intricate signaling pathways. An improved knowledge of mechanisms regulating uNK cells development and the cytokine network at the maternal-fetal interface of mice and humans might be useful to harness the power of these cells for maintenance of pregnancy. Cellular & Molecular Immunology. 2005;2(2):123-129.

  17. Offshore killer whale tracking using multiple hydrophone arrays.

    Gassmann, Martin; Henderson, E Elizabeth; Wiggins, Sean M; Roch, Marie A; Hildebrand, John A

    2013-11-01

    To study delphinid near surface movements and behavior, two L-shaped hydrophone arrays and one vertical hydrophone line array were deployed at shallow depths (Orcinus orca) using their emitted clicks. In addition, killer whale pulsed calls and high-frequency modulated (HFM) signals were localized using other standard techniques. Based on these tracks sound source levels for the killer whales were estimated. The peak to peak source levels for echolocation clicks vary between 170-205 dB re 1 μPa @ 1 m, for HFM calls between 185-193 dB re 1 μPa @ 1 m, and for pulsed calls between 146-158 dB re 1 μPa @ 1 m. PMID:24180762

  18. Sounds produced by Norwegian killer whales, Orcinus orca, during capture

    van Parijs, Sofie M.; Leyssen, Teo; Similä, Tiu

    2004-07-01

    To date very little is still known about the acoustic behavior of Norwegian killer whales, in particular that of individual whales. In this study a unique opportunity was presented to document the sounds produced by five captured killer whales in the Vestfjord area, northern Norway. Individuals produced 14 discrete and 7 compound calls. Two call types were used both by individuals 16178 and 23365 suggesting that they may belong to the same pod. Comparisons with calls documented in Strager (1993) showed that none of the call types used by the captured individuals were present. The lack of these calls in the available literature suggests that call variability within individuals is likely to be large. This short note adds to our knowledge of the vocal repertoire of this population and demonstrates the need for further studies to provide behavioural context to these sounds.

  19. The influence of Pichia killer toxins on the wine spoilage yeasts

    Urszula Błaszczyk

    2015-08-01

    Full Text Available Killer yeasts are able to produce toxins that antagonize the growth of susceptible yeasts cells of the same species or the ones that are related to them. Killer strains are resistant to their own toxins but can be sensitive to killer proteins of other yeasts. The killer proteins of Pichia spp. are known for its broad spectrum of antifungal activity including pathogens such as Candida albicans. The aim of the study was to investigate the potential of the partly purified killer toxins to inhibit the growth of selected yeast strains which can contribute to wine spoilage. Three Pichia killer yeast strains (CBS 1982, CBS 5759, CBS 7373 were used in the study. The killer protein secreted by Pichia anomala CBS 1982 was characterized by the highest antifungal activity. The most pronounced effect of the reduction of cell proliferation by killer toxin preparations was found after 2 and 20 h cultivation. Among the 13 tested strains, all Pichia killer toxin preparations inhibited the growth of Rhodotorula graminis Rg, Rhodotorula mucilaginosa Rm and Schizosaccharomyces pombe DSM 70576. Killer toxins produced by Pichia anomala CBS 1982 (K8 and CBS 5759 (K4 limited the growth of Candida pulcherrima K5 and Hanseniaspora guillermondii DSM 3432 after 2, 20 and 168 h of incubation. A significant reduction of Debaryomyces hansenii DSM 3428 biomass was observed in medium with the addition of one toxin preparation (Pichia anomala CBS 1982. The growth limitation of Candida glabrata DSM 6425, Hanseniaspora uvarum DSM 2768, Metchnikowia pulcherrima DSM 70321 and Cryptococcus laurentii DSM 70766 was noticed only after 2 hours cultivation in presence of killer protein preparations. The killer toxins could be used in the food industry as selective tools to control infections during the fermentation of wine and improve the quality of the final product.

  20. Stable isotopes of captive Cetaceans (Killer Whales and Bottlenose dolphins)

    Caut, Stéphane; Laran, Sophie; Garcia-Hartmann, Emmanuel; Das, Krishna

    2011-01-01

    There is currently a great deal of interest in using stable-isotope methods to investigate diet, trophic level and migration movement in wild cetaceans. Fundamental to the interpretation of these methods is the need to understand how diet isotopic values are reflected in consumer tissues. In this study, we investigated patterns of isotopic discrimination between diet and blood constituents of two species of cetaceans (killer whale, Orcinus orca and 19 bottlenose dolphin, Tursiops truncutus) f...

  1. STAT4-associated natural killer cell tolerance following liver transplantation

    Jamil, K M; Hydes, T.J.; Cheent, K.S.; Cassidy, S A; Traherne, J. A.; Jayaraman, J.; Trowsdale, J.; Alexander, G J; Little, A M; McFarlane, H.; Heneghan, M. A.; Purbhoo, M.A.; Khakoo, S I

    2016-01-01

    Objective: Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. Design: Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using ...

  2. Modeling cognitive and tactical aspects in hunter-killer missions

    Berman, Ohad

    2006-01-01

    Approved for public release; distribution is unlimited In this thesis, we present a Markov-based probability model for a human operated system of aerial hunter-killers attacking time-sensitive targets. We explore the effect of two resources -- time and supply of munitions -- and some cognitive aspects of the human operator on the performance of the system in different operational scenarios. We model the combat mission as a sequence of engagements; each of which includes a classificati...

  3. Toxicity of a plant based mosquito repellent/killer

    Singh, Bhoopendra; Singh, Prakash Raj; Mohanty, Manoj Kumar

    2012-01-01

    The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant base...

  4. Role of inositol phospholipid signaling in natural killer cell biology

    Gumbleton, Matthew; Kerr, William G.

    2013-01-01

    Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...

  5. Natural killer cells in non-hematopoietic malignancies

    Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie

    2012-01-01

    Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for...

  6. Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis

    Jaeger, B. N.; Donadieu, J.; Cognet, C.; Bernat, C.; Ordonez-Rueda, D.; Barlogis, V.; Mahlaoui, N.; Fenis, A.; Narni-Mancinelli, E.; Beaupain, B.; Bellanne-Chantelot, C.; Bajenoff, M.; Malissen, B.; Malissen, M; Vivier, E.

    2012-01-01

    Natural killer (NK) cells are bone marrow (BM)–derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation...

  7. Polyfunctionality of natural killer cell in healthy donors

    Yupanun WUTTI-IN; Preeyanat VONGCHAN; Thananchai, Hathairat

    2016-01-01

    Background: Natural killer (NK) cells are important guards of the innate immune system, which act by performing as primary effector cells in viral infections. NK cell function is regulated by the engagement of activating and/or inhibitory receptors on individual NK cell surfaces. Subsequent to activation, the release of preformed cytolytic granules or cytokines occurs. Recently, the polyfunctionality of NK cells has been described as a potent NK cell subset that mediates antiviral response in...

  8. Experimental evidence for action imitation in killer whales (Orcinus orca).

    Abramson, José Z; Hernández-Lloreda, Victoria; Call, Josep; Colmenares, Fernando

    2013-01-01

    Comparative experimental studies of imitative learning have focused mainly on primates and birds. However, cetaceans are promising candidates to display imitative learning as they have evolved in socioecological settings that have selected for large brains, complex sociality, and coordinated predatory tactics. Here we tested imitative learning in killer whales, Orcinus orca. We used a 'do-as-other-does' paradigm in which 3 subjects witnessed a conspecific demonstrator's performance that included 15 familiar and 4 novel behaviours. The three subjects (1) learned the copy command signal 'Do that' very quickly, that is, 20 trials on average; (2) copied 100 % of the demonstrator's familiar and novel actions; (3) achieved full matches in the first attempt for 8-13 familiar behaviours (out of 15) and for the 2 novel behaviours (out of 2) in one subject; and (4) took no longer than 8 trials to accurately copy any familiar behaviour, and no longer than 16 trials to copy any novel behaviour. This study provides experimental evidence for body imitation, including production imitation, in killer whales that is comparable to that observed in dolphins tested under similar conditions. These findings suggest that imitative learning may underpin some of the group-specific traditions reported in killer whales in the field. PMID:22875725

  9. Divergence of a stereotyped call in northern resident killer whales.

    Grebner, Dawn M; Parks, Susan E; Bradley, David L; Miksis-Olds, Jennifer L; Capone, Dean E; Ford, John K B

    2011-02-01

    Northern resident killer whale pods (Orcinus orca) have distinctive stereotyped pulsed call repertoires that can be used to distinguish groups acoustically. Repertoires are generally stable, with the same call types comprising the repertoire of a given pod over a period of years to decades. Previous studies have shown that some discrete pulsed calls can be subdivided into variants or subtypes. This study suggests that new stereotyped calls may result from the gradual modification of existing call types through subtypes. Vocalizations of individuals and small groups of killer whales were collected using a bottom-mounted hydrophone array in Johnstone Strait, British Columbia in 2006 and 2007. Discriminant analysis of slope variations of a predominant call type, N4, revealed the presence of four distinct call subtypes. Similar to previous studies, there was a divergence of the N4 call between members of different matrilines of the same pod. However, this study reveals that individual killer whales produced multiple subtypes of the N4 call, indicating that divergence in the N4 call is not the result of individual differences, but rather may indicate the gradual evolution of a new stereotyped call. PMID:21361462

  10. Involvement of cell wall beta-glucan in the action of HM-1 killer toxin.

    Kasahara, S; Ben Inoue, S; Mio, T; Yamada, T; Nakajima, T; Ichishima, E; Furuichi, Y; Yamada, H

    1994-07-01

    HM-1 killer toxin secreted from Hansenula mrakii inhibits the growth of Saccharomyces cerevisiae cells by interfering with beta-1,3-glucan synthesis. We found that HM-1 killer toxin killed intact cells but not protoplasts. In addition, cells lacking the functional KRE6 allele (kre6 delta) became resistant to higher concentration of HM-1 killer toxin. As reported by Roemer and Bussey [(1991) Proc. Natl. Acad. Sci. 88 11295-11299], cells lacking functional KRE6 had a reduced level of the cell wall beta-1,6-glucan compared to that in cells harboring the normal KRE6. These results suggest that the cell wall beta-glucan is involved in the action of HM-1 killer toxin. Addition of HM-1 killer toxin with several kinds of oligosaccharides revealed that either beta-1,3- or beta-1,6-glucan blocked the cytocidal action of HM-1 killer toxin whereas alpha-1,4-glucan and chitin did not. Mannan also interfered with HM-1 killer toxin action, but this inhibitory effect was much weaker than that observed with beta-1,3- or beta-1,6-glucans. Thus, it appears that the cell wall beta-glucan interacts with HM-1 killer toxin, and that this toxin-beta-glucan commitment is required for the action of HM-1 killer toxin. PMID:8026578

  11. Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions

    Song, Haifeng; Josleyn, Nicole; Janosko, Krisztina; Skinner, Jeff; Reeves, R. Keith; Cohen, Melanie; Jett, Catherine; Johnson, Reed; Blaney, Joseph E.; Bollinger, Laura; Jennings, Gerald; Jahrling, Peter B

    2013-01-01

    Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta), we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results show...

  12. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F.I.; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L. J. M.

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposur...

  13. ASSESSMENT OF MEDICATION ADHERENCE AND FACTORS AFFECTING TO MEDIACTION ADHERENCE IN ASTHMA PATIENTS BY CLINICAL PHARMACIST

    Hinchageri S. S

    2012-03-01

    Full Text Available Asthma is a major public health problem affecting a large number of individuals of all ages. The effectiveness of medications depends not only on the efficacy and appropriateness of the drugs used, but also on patient adherence to the intended regimen. Adherence with medication regimens is essential for attaining maximal therapeutic benefits. The main objective of the study was to assess the medication adherence and to identify the reasons for non-adherence to prescribed therapy. The medication adherence was assessed by using Morisky Medication Adherence Assessment questionnaires. Assessment of patient’s adherence from baseline to first follow up showed a mean increase in medication adherence level of 2.735 ± 0.1762 and P < 0.0001 which is statistically significant. Assessment of patient’s adherence from baselines to second follow up shows a mean increase of 3.211 ± 0.172 and P < 0.0001 which is statistically significant. The study concludes that pharmacist provided patient counseling found to have significant influence on improvement in the patient’s adherence to prescribed therapy.

  14. On World Religion Adherence Distribution Evolution

    Ausloos, M.; Petroni, F.

    2008-01-01

    Religious adherence can be considered as a degree of freedom, in a statistical physics sense, for a human agent belonging to a population. The distribution, performance and life time of religions can thus be studied having in mind heterogeneous interacting agent modeling in mind. We present a comprehensive analysis of 58 so called religion (to be better defined in the main text) evolutions, as measured through their number of adherents between 1900 and 2000, - data taken from the World Christ...

  15. Adherence of Staphylococcus epidermidis to intraocular lenses.

    Griffiths, P G; Elliot, T. S.; McTaggart, L

    1989-01-01

    We have demonstrated, with an in vitro model, that Staphylococcus epidermidis is able to colonise intraocular lenses. Adherent organisms were quantitated by light microscopy, scanning electron microscopy, and viable counting. Bacterial adherence was associated with production of a polysaccharide glycocalyx. Organisms which were attached to the lenses were resistant to apparently bactericidal concentrations of antibiotics, as determined by conventional testing. We speculate on the role of colo...

  16. Adenomyosis in pregnancy mimicking morbidly adherent placenta

    Tongsong, Theera; Khunamornpong, Surapan; Sirikunalai, Panarat; Jatavan, Thanate

    2014-01-01

    The objective of this study was to illustrate a false-positive diagnosis of adherent placenta due to underlying adenomyosis. A 34-year-old woman was diagnosed for placenta previa totalis with adherent placenta at 33 weeks, based on the findings of loss of clear space or distinguishing outline separating the placenta and uterine wall, presence of intraplacental lacunae and densely atypical vessels in the lesion. Caesarean hysterectomy was performed at 35 weeks. Pathological findings revealed p...

  17. Motivational factors of adherence to cardiac rehabilitation

    Shahsavari, Hooman; Shahriari, Mohsen; Alimohammadi, Nasrollah

    2012-01-01

    Background: Main suggested theories about patients’ adherence to treatment regimens recognize the importance of motivation in positive changes in behaviors. Since cardiac diseases are chronic and common, cardiac rehabilitation as an effective prevention program is crucial in management of these diseases. There is always concern about the patients’ adherence to cardiac rehabilitation. The aim of this study was to describe the motivational factors affecting the patients’ participation and compl...

  18. Effect of UV radiation on the killer phenotype in the wine yeast-saccharomycetes and spontaneous variation of this character

    Spontaneous and ultraviolet-induced changeabilities of wine yeasts from the killer state to sensitive one have been studied. Observed often spontaneous changes of killer and neutral phenotypes under laboratory store conditions as well as high mutation frequency of genetic elements responsible for the killer indication on ultraviolet irradiation testify that often encounterability in nature and in the production of sensitive yeasts is attributed to high frequency of mutation changes of the killer and neutral phenotypes to the sensitive state

  19. Understanding how adherence goals promote adherence behaviours: a repeated measure observational study with HIV seropositive patients

    Jones Gareth; Hawkins Kim; Mullin Rebecca; Nepusz Tamás; Naughton Declan P; Sheeran Paschal; Petróczi Andrea

    2012-01-01

    Abstract Background The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95%) of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80%) of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investiga...

  20. Microbicide clinical trial adherence: insights for introduction.

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

    2013-01-01

    After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044

  1. Microbicide clinical trial adherence: insights for introduction

    Cynthia Woodsong

    2013-04-01

    Full Text Available After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1 Adherence measurement in clinical trials, (2 Comprehension of use instructions/Instructions for use, (3 Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4 Partner influence on use, (5 Retention and continuation and (6 Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

  2. File list: InP.Bld.20.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available InP.Bld.20.AllAg.Natural_Killer_Cells mm9 Input control Blood Natural Killer Cells ...SRX338032,SRX338020,SRX338022,SRX338031 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Natural_Killer_Cells.bed ...

  3. File list: InP.Bld.05.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available InP.Bld.05.AllAg.Natural_Killer_Cells mm9 Input control Blood Natural Killer Cells ...SRX338020,SRX338031,SRX338032,SRX338022 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Natural_Killer_Cells.bed ...

  4. File list: InP.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available InP.Bld.50.AllAg.Natural_Killer_Cells mm9 Input control Blood Natural Killer Cells ...SRX338032,SRX338020,SRX338022,SRX338031 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Natural_Killer_Cells.bed ...

  5. File list: NoD.Bld.50.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

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  6. File list: NoD.Bld.10.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available NoD.Bld.10.AllAg.Natural_Killer_Cells mm9 No description Blood Natural Killer Cells... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.10.AllAg.Natural_Killer_Cells.bed ...

  7. File list: NoD.Bld.05.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available NoD.Bld.05.AllAg.Natural_Killer_Cells mm9 No description Blood Natural Killer Cells... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.05.AllAg.Natural_Killer_Cells.bed ...

  8. File list: NoD.Bld.20.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available NoD.Bld.20.AllAg.Natural_Killer_Cells mm9 No description Blood Natural Killer Cells... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.20.AllAg.Natural_Killer_Cells.bed ...

  9. File list: InP.Bld.10.AllAg.Natural_Killer_Cells [Chip-atlas[Archive

    Full Text Available InP.Bld.10.AllAg.Natural_Killer_Cells mm9 Input control Blood Natural Killer Cells ...SRX338032,SRX338022,SRX338020,SRX338031 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.Natural_Killer_Cells.bed ...

  10. Production of functional killer protein in batch cultures upon a shift from aerobic to anaerobic conditions

    Gildo Almeida da Silva

    2011-06-01

    Full Text Available The aim of this work was to study the production of functional protein in yeast culture. The cells of Saccharomyces cerevisiae Embrapa 1B (K+R+ killed a strain of Saccharomyces cerevisiae Embrapa 26B (K-R-in grape must and YEPD media. The lethal effect of toxin-containing supernatant and the effect of aeration upon functional killer production and the correlation between the products of anaerobic metabolism and the functional toxin formation were evaluated. The results showed that at low sugar concentration, the toxin of the killer strain of Sacch. cerevisiae was only produced under anaerobic conditions . The system of killer protein production showed to be regulated by Pasteur and Crabtree effects. As soon as the ethanol was formed, the functional killer toxin was produced. The synthesis of the active killer toxin seemed to be somewhat associated with the switch to fermentation process and with concomitant alcohol dehydrogenase (ADH activity.

  11. Construction of killer industrial yeast Saccharomyces cerevisiae HAU-1 and its fermentation performance

    Bijender K. Bajaj

    2010-06-01

    Full Text Available Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of the desirable fermentation characteristics like fast growth and fermentation rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to ferment at elevated temperatures etc. However, this yeast was found to be sensitive against the killer strains of Saccharomyces cerevisiae. In the present study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by protoplast fusion with Saccharomyces cerevisiae MTCC 475, a killer strain. The resultant fusants were characterized for desirable fermentation characteristics. All the technologically important characteristics of distillery yeast Saccharomyces cerevisiae HAU-1 were retained in the fusants, and in addition the killer trait was also introduced into them. Further, the killer activity was found to be stably maintained during hostile conditions of ethanol fermentations in dextrose or molasses, and even during biomass recycling.

  12. Yeast killer toxin-like anti-idiotypic antibodies.

    POLONELLI, L.; Morace, G

    1988-01-01

    Anti-idiotypic antibodies (anti-Ids) were raised in a rabbit against a murine monoclonal antibody (MAb) neutralizing the yeast killer toxin produced by a strain of Pichia (Hansenula) anomala. In an immunodiffusion test, the anti-Ids produced in the rabbit recognized the antigen-binding site of the MAb used as the immunogen (KT4) but not that of another heterologous MAb. The absence of any significant cross-reactivity among the anti-Ids raised in a rabbit for a heterologous MAb suggested that ...

  13. Google+ is Google's Facebook killer doomed to fail?

    Dino, G

    2012-01-01

    Do you have a Facebook profile? How about a Google+ page? Which do you prefer: Facebook or Google+? You may have both, but not use one as often as the other. You may have just one while waiting for the right time to join the other. The question is: When is the right time? Are you waiting to see which one is the better product? This issue has been the talk of the cybersphere since Google+ was released - will it be the Facebook killer that a number of other social media sites in the past have failed to become?

  14. A novel cell subset: Interferon-producing killer dendritic cells

    WANG JiongKun; XING FeiYue

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells (IKDCs). IKDCs not only secret type Ⅰ and type Ⅱ interferons to recognize and kill tumor cells effectively, but also express MHC-Ⅱ molecules to present antigens. Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  15. A novel cell subset:Interferon-producing killer dendritic cells

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  16. Natural killer T-cell lymphoma originating from the orbit

    DAI Wei; ZHONG Ming; SHEN Wei; ZOU Ke; BAI Chen-guang

    2012-01-01

    Natural killer T-cell lymphoma (NKTL) is a malignant neoplasm which usually involves the nasal cavity or paranasal sinuses,while an orbit origin is extremely rare.Here we report the clinical,radiological and histopathologic features of a patient with NKTL originating from the orbit.We analyzed the clinical and radiologic records in the whole course of the disease.We also reviewed the morphology and immunohistochemistry of the neoplasm biopsy,including the presence of CD56,CD3 and cytotoxic molecules.This case demonstrated that nasal-type NKTL with a poor prognosis can originate from the orbit.

  17. SoftKiller, a particle-level pileup removal method

    Cacciari, Matteo [Universite Paris Diderot, Paris (France); Sorbonne Universites, UPMC Univ Paris 06, UMR 7589, LPTHE, Paris (France); CNRS, UMR 7589, LPTHE, Paris (France); Salam, Gavin P. [CERN, PH-TH, Geneva 23 (Switzerland); Soyez, Gregory [IPhT, CEA Saclay, CNRS URA 2306, Gif-sur-Yvette Cedex (France)

    2015-02-01

    Existing widely used pileup removal approaches correct the momenta of individual jets. In this article we introduce an event-level, particle-based pileup correction procedure, SoftKiller. It removes the softest particles in an event, up to a transverse momentum threshold that is determined dynamically on an event-by-event basis. In simulations, this simple procedure appears to be reasonably robust and brings superior jet resolution performance compared to existing jet-based approaches. It is also nearly two orders of magnitude faster than methods based on jet areas. (orig.)

  18. Road Traffic Accidents - The Number One Killer in Libya

    Abdulmajid Ahmed Ali

    2007-01-01

    Full Text Available To The Editor: It is estimated that 1.26 million people worldwide died in 2000 from road traffic accidents, 90% of them in low and middle-income countries. In 2000, the road traffic injury mortality rate for the world was 20.8 per 100,000 populations (30.8 in males, 11.0 in females [1].The Arab population constitutes 3.6% of the world’s population and it owns 1% of the world’s vehicles. Its human losses as a result of road traffic accidents (RTA account for 4.8% of that of the world’s losses [2]. It is estimated that the annual cost of road crashes is about 1% of the Gross National Product (GNP in developing countries, 1.5 in transitional countries and 2% in highly motorised countries [3].In Libya the situation is worse. It is a sad fact that road traffic accidents are the number one killer in Libya. As a matter of fact I consider it to be an ‘epidemic’ in all sectors of the Libyan society. There is not a day that goes by in Libya without us hearing about families, young men, women and children getting killed in horrific car accidents.It is alarming that young children are knocked down on a daily basis by speeding young drivers, whose understanding of driving skills may have been acquired from "playstation games"! (You can watch some of the shameful video clips sent by some of these drivers on this link http://www.youtube.com/watch?v=doWEDjiHlVoI feel it is our responsibility as physicians observing the situation to raise awareness about the scale of the problem, possible causes, and how to tackle it. POSSIBLE CAUSES:• A driving licence in Libya is not issued on the basis of how much you know. Therefore the majority of drivers know little or nothing about the law.• Wearing seat belts is not compulsory in most parts of Libya. In some places, especially in the Eastern part of Libya, you could be penalised for wearing one. I was stopped many years ago by the traffic police in the Eastern part of Libya because I was wearing sunglasses

  19. Invariant natural killer T cell–natural killer cell interactions dictate transplantation outcome after α-galactosylceramide administration

    Kuns, Rachel D.; Morris, Edward S.; MacDonald, Kelli P.A.; Markey, Kate A.; Helen M. Morris; Raffelt, Neil C.; Banovic, Tatjana; Don, Alistair L. J.; Rowe, Vanessa; Burman, Angela C.; Clouston, Andrew D; Farah, Camile; Besra, Gurdyal S.; Illarionov, Petr A.; Smyth, Mark J

    2009-01-01

    Invariant natural killer T cells (iNKT cells) have pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. iNKT cells are activated through their T-cell receptors by glycolipid moieties (typically the α-galactosylceramide [α-GalCer] derivative KRN7000) presented within CD1d. We investigated the ability of modified α-GalCer molecules to differentially modulate alloreactivity and GVL. KRN7000 and the N-acyl variant, C20:2, were administered in multiple well-es...

  20. Echolocation signals of foraging killer whales (Orcinus orca)

    Au, Whitlow W. L.; Ford, John K. B.; Allman, Kelly A.

    2002-05-01

    Fish eating resident killer whales that frequent the coastal waters of Vancouver Island, Canada have a strong preference for chinook salmon. The whales in Johnston Strait often forage along the steep cliffs that extend into the water, echolocating their prey. Echolocation signals were measured with a four hydrophone symmetrical star array and the signals were simultaneous digitized at a sample rate of 500 kHz using a lunch-box PC. A portable VCR recorded the images from an underwater camera located close to the array center. Only signals emanated from close to the beam axis (1185 total) were chosen for a detailed analysis. Killer whales project very broad band echolocation signals (Q 1.3 to 1.5) that tend to have a bimodal frequency structure. Ninety seven percent of the signals had center frequencies between 45 and 80 kHz with a band-width between 35 and 50 kHz. The peak-to-peak source level of the echolocation signal decreased as a function of the one way transmission loss to the array. Source levels varied between 200 and 225 dB re 1 μPa. Using a model of target strength for chinook salmons, the echo levels from the echolocation signals are estimated for different ranges between whale and salmon.

  1. Stable isotopes of captive cetaceans (killer whales and bottlenose dolphins).

    Caut, Stéphane; Laran, Sophie; Garcia-Hartmann, Emmanuel; Das, Krishna

    2011-02-15

    There is currently a great deal of interest in using stable isotope methods to investigate diet, trophic level and migration in wild cetaceans. In order to correctly interpret the results stemming from these methods, it is crucial to understand how diet isotopic values are reflected in consumer tissues. In this study, we investigated patterns of isotopic discrimination between diet and blood constituents of two species of cetaceans (killer whale, Orcinus orca, and bottlenose dolphin, Tursiops truncatus) fed controlled diets over 308 and 312 days, respectively. Diet discrimination factors (Δ; mean ± s.d.) for plasma were estimated to Δ(13)C=2.3±0.6‰ and Δ(15)N=1.8±0.3‰, respectively, for both species and to Δ(13)C=2.7±0.3‰ and Δ(15)N=0.5±0.1‰ for red blood cells. Delipidation did not have a significant effect on carbon and nitrogen isotopic values of blood constituents, confirming that cetacean blood does not serve as a reservoir of lipids. In contrast, carbon isotopic values were higher in delipidated samples of blubber, liver and muscle from killer whales. The potential for conflict between fisheries and cetaceans has heightened the need for trophic information about these taxa. These results provide the first published stable isotope incorporation data for cetaceans, which are essential if conclusions are to be drawn on issues concerning trophic structures, carbon sources and diet reconstruction. PMID:21270301

  2. Disseminated mycosis in a killer whale (Orcinus orca).

    Abdo, Walied; Kawachi, Takeshi; Sakai, Hiroki; Fukushi, Hideto; Kano, Rui; Shibahara, Tomoyuki; Shirouzu, Hiroshi; Kakizoe, Yuko; Tuji, Hajime; Yanai, Tokuma

    2012-01-01

    Hematological findings in a female killer whale (Orcinus orca) undergoing rehabilitation after sudden severe anorexia revealed continuing increases in serum lactate dehydrogenase and aspartate aminotransferase activities as well as fibrinogen concentration. Serologic evidence of herpesvirus infection and skin vesicles were detected 2 weeks into the treatment regimen of antibiotics and corticosteroids. The whale showed signs of improvement after treatment with anti-herpesvirus drugs, but sudden severe anorexia reappeared, along with marked elevation of fibrinogen concentration that continued until the death. Postmortem examination revealed multiple light tan foci of necrosis in the skeletal and cardiac muscles, and lung consolidation. Microscopic findings indicated disseminated fungal granulomas in the skeletal and cardiac muscles, as well as myocarditis, mycotic embolic thromboarteritis of cardiac blood vessels, and bronchopneumonia with numerous typical Aspergillus-like fungi. Mucor-like structures in granulomas in the heart and skeletal muscle and Aspergillus-like fungi in the lungs were identified using periodic acid-Schiff, Gomori methenamine silver stain, and immunohistochemistry. The present case involves dual infection with Mucor and Aspergillus species in a killer whale with concurrent herpesvirus. PMID:22362957

  3. Cytokine-induced killer cell transplantation: an innovative adoptive therapy

    Binh Thanh Vu

    2016-03-01

    Full Text Available Cytokine-induced killer (CIK cells areeffector immune cells with anti-tumor potency of T lymphocytes as well as non-major histocompatibility complex restricted elimination of natural killer cells. Preclinical models have shown that CIK cells have strong anti-tumor killing capacity against a variety of blood cancers and solid tumors. Clinical studies confirm the advantages of CIK cells, including the safety of CIK cell therapy in patients with advanced cancer. A preeminent property of CIK cells, which may help them to overcome some of the limitations of other adoptive immunotherapy strategies, is their ability to be expanded ex vivo to high numbers. Their robust in vitro proliferation provides adequate quantity for multiple adoptive infusions. The tumor-killing capacity of CIK cells is mainly based on the interaction between NKG2D molecules on CIK cells and MIC A/B or ULBP molecules on tumor cells. Moreover, CIK cells have a reduced allo-reactivity across HLA-barriers. This review summarizes the clinical applications of CIK cells and updates of combining CIK cells with other therapies. This review highlights the benefits of CIK cell use in clinical treatment of cancer. [Biomed Res Ther 2016; 3(3.000: 533-541

  4. RNA polymerase of the killer virus of yeast

    The L/sub A/ and M double-stranded (ds) RNA segments of the cytoplasmically inherited killer virus of Saccharomyces cerevisiae are encapsidated in virions that contain a DNA-independent transcriptase activity. This enzyme catalyzes the synthesis of full-length (+) stranded copies of the genomic dsRNA segments, denoted l/sub A/ and m. The L/sub A/ dsRNA segment appears to encode the major capsid protein in which both dsRNA molecules are encapsidated, while M dsRNA encodes products responsible for the two killer phenotypes of toxin production and resistance to toxin. Proteins extracted from transcriptionally active virions fail to cross-react with antibody to yeast DNA-dependent RNA polymerases, suggesting that none of the subunits of the host cell polymerases are active in viral transcription. Sequence analysis of the in vitro transcripts reveals neither to be 3'-terminally polyadenylated, although m contains an apparent internal polyA-like tract. In the presence of any three ribonucleoside triphosphates (0.5 mM), the fourth ribonucleoside triphosphate shows an optimal rate of incorporation into transcript at a concentration of 20 μM. However, in a 3-hour reaction, the yield of a product RNA increases with the concentration of the limiting ribonucleotide up to 0.5 mM. Gel electrophoresis of the reaction products reveals that increasing the substrate concentration accelerates the appearance of radioactivity in full-length l/sub A/ and m transcripts

  5. Impact of Adherence Counseling Dose on Antiretroviral Adherence and HIV Viral Load among HIV-Infected Methadone Maintained Drug Users

    Cooperman, Nina A.; Heo, Moonseong; Berg, Karina M.; Li, Xuan; Litwin, Alain H.; Nahvi, Shadi; Arnsten, Julia H.

    2012-01-01

    Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence couns...

  6. Improving medication adherence in patients with hypertension

    Hedegaard, Ulla; Kjeldsen, Lene Juel; Pottegård, Anton; Henriksen, Jan Erik; Lambrectsen, Jess; Hangaard, Jørgen; Hallas, Jesper

    2015-01-01

    medication adherence in hypertensive patients. Motivational interviewing was a key element of the intervention. METHODS: Patients (N=532) were recruited from 3 hospital outpatient clinics and randomized to usual care or a 6-month pharmacist intervention comprising collaborative care, medication review......, tailored adherence counselling including motivational interviewing and telephone follow-ups. The primary outcome was composite medication possession ratio (MPR) to antihypertensive and lipid-lowering agents, at one-year follow-up, assessed by analyzing pharmacy records. Secondary outcomes at 12 months...... included persistence to medications, blood pressure, hospitals admission and a combined clinical endpoint of cardiovascular death, stroke or acute myocardial infarction. RESULTS: At 12 months, 20.3% of the patients in the intervention group (N=231) were non-adherent (MPR < 0.80) compared with 30.2% in the...

  7. Low-frequency signals produced by Northeast Atlantic killer whales (Orcinus orca).

    Samarra, Filipa I P; Deecke, Volker B; Miller, Patrick J O

    2016-03-01

    Killer whale acoustic behavior has been extensively investigated; however, most studies have focused on pulsed calls and whistles. This study reports the production of low-frequency signals by killer whales at frequencies below 300 Hz. Recordings were made in Iceland and Norway when killer whales were observed feeding on herring and no other marine mammal species were nearby. Low-frequency sounds were identified in Iceland and ranged in duration between 0.14 and 2.77 s and in frequency between 50 and 270 Hz, well below the previously reported lower limit for killer whale tonal sounds of 500 Hz. Low-frequency sounds appeared to be produced close in time to tail slaps, which are indicative of feeding attempts, suggesting that these sounds may be related to a feeding context. However, their precise function is unknown, and they could be the by-product of a non-vocal behavior rather than a vocal signal deliberately produced by the whales. Although killer whales in Norway exhibit similar feeding behavior, this sound has not been detected in recordings from Norway to date. This study suggests that, like other delphinids, killer whales produce low-frequency sounds, but further studies will be required to understand whether similar sounds exist in other killer whale populations. PMID:27036251

  8. Genistein inhibits human TNF-α-induced porcine endothelial cell adhesiveness for human monocytes and natural killer cells

    2002-01-01

    Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We investigated the role of protein tyrosine phosphorylation in the induction of expression of E-sclectin and vascular cell adhesion molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells (PBNK), after rhTNF-α-stimulation of porcine aortic endothelial cells (PAEC) in vitro, rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated activation of protein tyrosine kinases (PTKs) in PAEC in a dose-dependent manner. Flow cytometric analysis showed that genistein inhibited the upregulation of E-selectin and VCAM-1 by rhTNF-α. These results suggest that PTKs may regulate the expression of E-selectin and VCAM-1 on PAEC and the adherence of PBMo and PBNK induced by rhTNF-α. Moreover, dietary genistein, used as an adhesion antagonist, may contribute to managing the cell-mediated rejection in the clinical application.

  9. [Adherence to statins: updates and practical proposals].

    Bauwens, Marine; Schneider, Marie-paule; Nanchen, David

    2016-03-01

    Statins are an established treatment for dyslipidemia, because they were shown to decrease the cardiovascular risk by 25%. However, one third of patients using statins don't take them regularly. Statin intolerance is an important risk factor for nonadherence, but health literacy and lack of education regarding the cardiovascular benefits are also important triggers for poor adherence to statins. A better communication between the caregiver and his patient, by taking patient's perspectives into account could help find effective solutions. This article reviews the issue of statins adherence and suggests solutions to improve it. PMID:27089601

  10. Positioning Effects of KillerRed inside of Cells correlate with DNA Strand Breaks after Activation with Visible Light

    Waldemar Waldeck, Gabriele Mueller, Manfred Wiessler, Katalin Tóth, Klaus Braun

    2011-01-01

    Full Text Available Fluorescent proteins (FPs are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED, used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS resulting in photokilling processes. It is a given that the extent of the KRED's cell toxicity depends on its subcellular localization. Evidences are documented that the nuclear lamina as well as especially the chromatin are critical targets for KRED-mediated ROS-based DNA damaging. Here we investigated the damaging effects of the KRED protein fused to the nuclear lamina and to the histone H2A DNA-binding protein. We detected a frequency of DNA strand breaks, dependent first on the illumination time, and second on the spatial distance between the localization at the chromatin and the site of ROS production. As a consequence we could identify defined DNA bands with 200, 400 and (600 bps as most prominent degradation products, presumably representing an internucleosomal DNA cleavage induced by KRED. These findings are not restricted to the detection of programmed cell death processes in the therapeutic field like PDT, but they can also contribute to a better understanding of the structure-function relations in the epigenomic world.

  11. Positioning Effects of KillerRed inside of Cells correlate with DNA Strand Breaks after Activation with Visible Light

    Waldeck, Waldemar; Mueller, Gabriele; Wiessler, Manfred; Tóth, Katalin; Braun, Klaus

    2011-01-01

    Fluorescent proteins (FPs) are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED), used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS) resulting in photokilling processes. It is a given that the extent of the KRED's cell toxicity depends on its subcellular localization. Evidences are documented that the nuclear lamina as well as especially the chromatin are critical targets for KRED-mediated ROS-based DNA damaging. Here we investigated the damaging effects of the KRED protein fused to the nuclear lamina and to the histone H2A DNA-binding protein. We detected a frequency of DNA strand breaks, dependent first on the illumination time, and second on the spatial distance between the localization at the chromatin and the site of ROS production. As a consequence we could identify defined DNA bands with 200, 400 and (600) bps as most prominent degradation products, presumably representing an internucleosomal DNA cleavage induced by KRED. These findings are not restricted to the detection of programmed cell death processes in the therapeutic field like PDT, but they can also contribute to a better understanding of the structure-function relations in the epigenomic world. PMID:21278894

  12. The Patient's Perspective: Adherence or Non-adherence to Asthma Controller Therapy?

    Ulrik, Charlotte Suppli; Backer, V; Soes-Petersen, U; Lange, Peter; Harving, H; Plaschke, PP

    2006-01-01

    STUDY OBJECTIVE: Adherence with controller therapy poses a major challenge to the effective management of persistent asthma. The aim of this study was to explore the patient-related aspects of adherence among adult asthmatics. DESIGN AND PARTICIPANTS: The participants (n = 509 adult asthmatics......), recruited from all parts of Denmark, answered the questionnaire concerning asthma knowledge, attitudes, adherence, and treatment through the Internet. RESULTS: A total of 67% of the patients were prescribed inhaled corticosteroids (ICS). However, according to Global Initiative for Asthma (GINA...

  13. Adherence to physiotherapy clinical guideline acute ankle injury and determinants of adherence: a cohort study

    van Beers Hans

    2007-05-01

    Full Text Available Abstract Background Clinical guidelines are considered important instruments to improve quality in health care. In physiotherapy, insight in adherence to guidelines is limited. Knowledge of adherence is important to identify barriers and to enhance implementation. Purpose of this study is to investigate the ability to adherence to recommendations of the guideline Acute ankle injury, and to identify patient characteristics that determine adherence to the guideline. Methods Twenty-two physiotherapists collected data of 174 patients in a prospective cohort study, in which the course of treatment was systematically registered. Indicators were used to investigate adherence to recommendations. Patient characteristics were used to identify prognostic factors that may determine adherence to the guideline. Correlation between patient characteristics and adherence to outcome-indicators (treatment sessions, functioning of patient, accomplished goals was calculated using univariate logistic regression. To calculate explained variance of combined patient characteristics, multivariate analysis was performed. Results Adherence to individual recommendations varied from 71% to 100%. In 99 patients (57% the physiotherapists showed adherence to all indicators. Adherence to preset maximum of six treatment sessions for patients with severe ankle injury was 81% (132 patients. The odds to receive more than six sessions were statistically significant for three patient characteristics: females (OR:3.89; 95%CI: 1.41–10.72, recurrent sprain (OR: 6.90; 95%CI: 2.34 – 20.37, co-morbidity (OR: 25.92; 95% CI: 6.79 – 98.93. All factors together explained 40% of the variance. Inclusion of physiotherapist characteristics in the regression model showed that work-experience reduced the odds to receive more than six sessions (OR: 0.2; 95%CI: 0.06 – 0.77, and increased explained variance to 45%. Conclusion Adherence to the clinical guideline Acute ankle sprain showed that the

  14. Primary non-adherence to prescribed medication in general practice

    Linnet, Kristján; Halldórsson, Matthías; Thengilsdóttir, Gudrún;

    2013-01-01

    Primary non-adherence refers to the patient not redeeming a prescribed medication at some point during drug therapy. Research has mainly focused on secondary non-adherence. Prior to this study, the overall rate of primary non-adherence in general practice in Iceland was not known.......Primary non-adherence refers to the patient not redeeming a prescribed medication at some point during drug therapy. Research has mainly focused on secondary non-adherence. Prior to this study, the overall rate of primary non-adherence in general practice in Iceland was not known....

  15. Comparison of europium and chromium release assays: cytotoxicity in healthy individuals and patients with cervical carcinoma.

    von Zons, P; Crowley-Nowick, P; Friberg, D; Bell, M.; Koldovsky, U; Whiteside, T L

    1997-01-01

    Natural killer (NK) and lymphokine-activated killer (LAK) cell activities were measured in peripheral blood obtained from healthy women to compare a standard 51Cr release assay with a nonradioactive europium (Eu3+) release assay based on time-resolved fluorescence. The two types of cytotoxicity assays were first compared in paired determinations performed on 28 samples of peripheral blood mononuclear cells obtained from healthy women who had normal pap smears or no biopsy evidence of cervical...

  16. Adherence to methotrexate in rheumatoid arthritis

    Bliddal, Henning; Eriksen, Stine A; Christensen, Robin;

    2015-01-01

    Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis/contact, with at...

  17. Adherence to Exercise and Physical Activity: Preface.

    Morgan, William P.; Dishman, Rod K.

    2001-01-01

    Introduces a collection of papers on adherence to exercise programs and physical activity from the 2000 American Academy of Kinesiology and Physical Education conference, which included research on middle school boys and girls, college men and women, and men and women in the later years, as well as on the more traditional subject of middle aged…

  18. Barriers to adherence in cystic fibrosis

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

    Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack of...

  19. E-health strategies to support adherence

    Adherence to healthy behaviors and self-care strategies is a concern among clinicians. E-health applications, such as the internet, personal communication devices, electronic health records and web portals, and electronic games, may be a way to provide health information in a way that is reliable, c...

  20. Understanding adherence to web-based interventions

    Kelders, S.M.

    2012-01-01

    Although eHealth technologies and especially web-based interventions for the promotion of health and health related behavior have been shown to be effective, the impact is hindered by non-adherence: while many eHealth interventions reach a large group of participants, not all of these participants c

  1. Activation of Natural Killer cells during microbial infections

    Amir eHorowitz

    2012-01-01

    Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.

  2. Operational Performance Analysis of Passive Acoustic Monitoring for Killer Whales

    Matzner, Shari; Fu, Tao; Ren, Huiying; Deng, Zhiqun; Sun, Yannan; Carlson, Thomas J.

    2011-09-30

    For the planned tidal turbine site in Puget Sound, WA, the main concern is to protect Southern Resident Killer Whales (SRKW) due to their Endangered Species Act status. A passive acoustic monitoring system is proposed because the whales emit vocalizations that can be detected by a passive system. The algorithm for detection is implemented in two stages. The first stage is an energy detector designed to detect candidate signals. The second stage is a spectral classifier that is designed to reduce false alarms. The evaluation presented here of the detection algorithm incorporates behavioral models of the species of interest, environmental models of noise levels and potential false alarm sources to provide a realistic characterization of expected operational performance.

  3. Impact of polysialylated CD56 on natural killer cell cytotoxicity

    Kaltschmidt Christian

    2007-08-01

    Full Text Available Abstract Background Siglec-7, a sialic acid binding inhibitory receptor expressed by NK cells is masked in vivo by a so far unknown ligand. It shows a strong binding prevalence for α-2,8-linked disialic acids in vitro. Results Here we describe the expression of PSA-NCAM (α-2,8-linked polysialic acid modified NCAM on functional adult peripheral blood natural killer cells and examine its possible role in masking Siglec-7. Unmasking of Siglec-7 using Clostridium perfringens neuraminidase massively reduces NK cell cytotoxicity. By contrast a specific removal of PSA using Endo-NF does not lead to a reduction of NK cell cytotoxicity. Conclusion The results presented here therefore indicate that PSA-NCAM is not involved in masking Siglec-7.

  4. Prolonged treatment response in aggressive natural killer cell leukemia.

    Osuji, N; Matutes, E; Morilla, A; Del Giudice, I; Wotherspoon, A; Catovsky, D

    2005-05-01

    We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly. The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis. Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow). The subsequent clinical course has been indolent, but this may have been influenced by treatment. Treatment consisted sequentially of splenectomy, intravenous pentostatin and the combination of cyclosporine A and recombinant human erythropoietin and has resulted in survival of over 48 months. We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders. PMID:16019515

  5. Vulnerability of a killer whale social network to disease outbreaks

    Guimarães, Paulo R., Jr.; de Menezes, Márcio Argollo; Baird, Robin W.; Lusseau, David; Guimarães, Paulo; Dos Reis, Sérgio F.

    2007-10-01

    Emerging infectious diseases are among the main threats to conservation of biological diversity. A crucial task facing epidemiologists is to predict the vulnerability of populations of endangered animals to disease outbreaks. In this context, the network structure of social interactions within animal populations may affect disease spreading. However, endangered animal populations are often small and to investigate the dynamics of small networks is a difficult task. Using network theory, we show that the social structure of an endangered population of mammal-eating killer whales is vulnerable to disease outbreaks. This feature was found to be a consequence of the combined effects of the topology and strength of social links among individuals. Our results uncover a serious challenge for conservation of the species and its ecosystem. In addition, this study shows that the network approach can be useful to study dynamical processes in very small networks.

  6. Hepatic steatosis: A benign disease or a silent killer

    2008-01-01

    Steatosis is a common feature of many liver diseases, namely non-alcoholic steatohepatitis (NASH) and hepatitis C virus (HCV) infection, but the pathogenic mechanisms differ. Insulin resistance (IR), a key feature of metabolic syndrome, is crucial for NASH development, associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis. This may have potential implications for new drug therapy. In HCV-related disease, steatosis impacts both fibrosis progression and response to treatment. Steatosis in HCV-related disease relates to both viral factors (HCV genotype 3), and host factors (alcohol consumption, overweight, hyperlipidemia, diabetes). Among others, IR is a recognized factor. Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors. Thus, hepatic steatosis should not be considered a benign feature, but rather a silent killer.

  7. Distribution of natural killer cell receptors in HIV infected individuals

    JIANG Yong-jun; SHANG Hong; ZHANG Zi-ning; DIAO Ying-ying; GENG Wen-qing; DAI Di; LIU Jing; WANG Ya-nan; ZHANG Min; HAN Xiao-xu

    2007-01-01

    @@ Natural killer (NK) cells are bone marrow derived,large granular lymphocytes, comprising approximately 10% to 20% of the mononuclear cell fraction in normal peripheral blood. They form a part of the first line defense mechanism against tumoural and viral spreading.1-4 Unlike T and B cells, NK cells do not require gene rearrangement for assembly of their receptor genes; rather, NK cells discriminate potential target cells based on the levels of self major histocompatibility complex (MHC) class Ⅰ expression on such cells.5,6 There are two kinds of NK cell receptors.2,7,8 Inhibitory receptors recognize MHC class Ⅰ molecules and deliver a downregulatory signal that inactivates the lyric machinery of NK cells. Stimulatory receptors expressed by NK cells deliver an activation signal.

  8. Natural killer cells: walking three paths down memory lane.

    Min-Oo, Gundula; Kamimura, Yosuke; Hendricks, Deborah W; Nabekura, Tsukasa; Lanier, Lewis L

    2013-06-01

    Immunological memory has traditionally been regarded as a unique feature of the adaptive immune response, mediated in an antigen-specific manner by T and B lymphocytes. All other hematopoietic cells, including natural killer (NK) cells, are classified as innate immune cells, which have been considered short-lived but can respond rapidly against pathogens in a manner not thought to be driven by antigen. Interestingly, NK cells have recently been shown to survive long term after antigen exposure and subsequently mediate antigen-specific recall responses. In this review, we address the similarities between, and the controversies surrounding, three major viewpoints of NK memory that have arisen from these recent studies: (i) mouse cytomegalovirus (MCMV)-induced memory; (ii) cytokine-induced memory; and (iii) liver-restricted memory cells. PMID:23499559

  9. Natural killer cells: Biology, functions and clinical relevance

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction. Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1 killer immunoglobulin like receptors-KIR, 2 C-type lectin receptors,3natural citotoxicity receptors-NCR and 4 Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

  10. Regulation of Natural Killer Cell Function by STAT3

    Nicholas eCacalano

    2016-04-01

    Full Text Available Natural killer (NK cells, key members of a distinct hempatopoietic lineage, innate lymphoid cells (ILCs, are critical effectors that mediate cytotoxicity toward tumor and virally-infected cells but also regulate inflammation, antigen presentation and the adaptive immune response. It has been shown that NK cells can regulate the development and activation of many other components of the immune response such as dendritic cells, which in turn, modulate the function of NK cells in multiple synergistic feed back loops driven by cell-cell contact and the secretion of cytokines and chemokines that control effector function and migration of cells to sites of immune activation. The Signal Transducer and Activator of Transcription (STAT-3 is involved in driving almost all of the pathways that control NK cytolytic activity as well as the reciprocal regulatory interactions between NK cells and other components of the immune system. In the context of tumor immunology, NK cells are a first line of defense that eliminates pre-cancerous and transformed cells early in the process of carcinogenesis, through a mechanism of immune surveillance. Even after tumors become established, NK cells are critical components of anti-cancer immunity: dysfunctional NK cells are often found in the peripheral blood of cancer patients and the lack of NK cells in the tumor microenvironment often correlates with poor prognosis. The pathways and soluble factors activated in tumor-associated NK cells, cancer cells, and regulatory myeloid cells which determine the outcome of cancer immunity are all critically regulated by STAT3. Using the tumor microenvironment as a paradigm, we present here an overview of the research that has revealed fundamental mechanisms through which STAT3 regulates all aspects of natural killer cell biology, including NK development, activation, target cell killing, and fine tuning of the innate and adaptive immune responses.

  11. Quantitation of natural killer cell precursors in man.

    Gharehbaghian, Ahmad; Haque, K M Gausul; Truman, Carol; Newman, John; Bradley, Benjamin A

    2002-02-01

    A technique was developed to measure the frequency of natural killer cell precursors (NKpf) in human peripheral blood mononuclear cell (PBMC) samples. Functional maturity of NK cells was reflected in their ability to lyse target cells from the K562 cell line. During the development of the technique, venous blood was taken from one healthy adult and assayed at different times to avoid individual variation. The technique was based on the principle of limiting dilution analysis. The NKpf assay was set up with a range of cell dilutions from 40,000 to 625 per 100 microl/well in 96-well culture plates. At the end of the culture period, the K562 cell line labelled with europium (Eu-K562) was added and the Eu-release was measured in culture supernatants using time-resolved fluorometry. The NKpf value differed between individuals and was influenced by the length of time in culture, being maximal at day 5. Maturation of NKp required the continuous presence of recombinant interleukin 2 (rIL-2), or rIL-15, both being equally effective. In the absence of cytokines, the functional NK cells declined rapidly beyond 24 h in culture. Irradiated allogeneic cells appeared to substitute in part for cytokines, but the numbers of allo-activated NKpf were lower than those observed when allo-activated NKpf were cultured with rIL-2. This suggested selective activation by the allogeneic stimulus of subsets of NKp or rIL-2-rescue of NKp subsets destined for apoptotic cell death. Alternatively, the increased frequency could have been attributable to activation of precursors of natural killer-T cells (NK-Tp). This assay is suitable for estimating the total number of precursors of functional NK cells in the blood of patients. PMID:11792377

  12. Hepatitis C Now Leading Infectious Disease Killer in U.S.

    ... nlm.nih.gov/medlineplus/news/fullstory_158651.html Hepatitis C Now Leading Infectious Disease Killer in U.S. ... May 4, 2016 (HealthDay News) -- The number of hepatitis C-linked deaths in the United States reached ...

  13. On the communicative significance of whistles in wild killer whales (Orcinus orca)

    Thomsen, Frank; Franck, Dierk; Ford, John

    2002-08-01

    Killer whales (Orcinus orca) use pulsed calls and whistles in underwater communication. Unlike pulsed calls, whistles have received little study and thus their function is poorly known. In this study, whistle activities of groups of individually known killer whales were compared quantitatively across behavioural categories. Acoustic recordings and simultaneous behavioural observations were made of northern resident killer whales off Vancouver Island in 1996 and 1997. Whistles were produced at greater rates than discrete calls during close-range behavioural activities than during long-range activities. They were the predominant sound-type recorded during socializing. The number of whistles per animal per minute was significantly higher during close-range behavioural activities than during long-range activities. Evidently, whistles play an important role in the close-range acoustic communication in northern resident killer whales.

  14. Hepatitis C Now Leading Infectious Disease Killer in U.S.

    ... Hepatitis C Now Leading Infectious Disease Killer in U.S. CDC notes that nearly 20,000 Americans died ... deaths in 2014, according to preliminary data from U.S. Centers for Disease Control and Prevention. Those tragically ...

  15. Adherent bacterial populations on the bovine rumen wall: distribution patterns of adherent bacteria.

    McCowan, R P; Cheng, K J; Costerton, J W

    1980-01-01

    Fourteen tissue sites from the bovine reticulo-rumen were examined by scanning electron microscopy to determine the distribution patterns of bacterial populations adhering to the epithelium. Although diet variations did not appear to influence the total number of tissue-adherent bacteria present in adult Herefords, diet affected their distribution. It appeared that the distribution of the bacterial populations may be directly affected by the physical state of the digesta. The digesta may be m...

  16. An Introductory Pharmacy Practice Experience on Improving Medication Adherence

    Darbishire, Patricia L.; Plake, Kimberly S.; Kiersma, Mary E.; White, Jessalynn K.

    2012-01-01

    Objective. To evaluate the impact of a medication adherence activity on introductory pharmacy practice experience students’ perceptions of patient adherence as well as student development of empathy and confidence in patient counseling.

  17. Target Strength of Southern Resident Killer Whales (Orcinus orca): Measurement and Modeling

    Xu, Jinshan; Deng, Zhiqun; Carlson, Thomas J.; Moore, Brian

    2012-04-04

    A major criterion for tidal power licensing in Washington’s Puget Sound is the management of the risk of injury to killer whales due to collision with moving turbine blades. An active monitoring system is being proposed for killer whale detection, tracking, and alerting that links to and triggers temporary turbine shutdown when there is risk of collision. Target strength (TS) modeling of the killer whale is critical to the design and application of any active monitoring system. A 1996 study performed a high-resolution measurement of acoustic reflectivity as a function of frequency of a female bottlenose dolphin (2.2 m length) at broadside aspect and TS as a function of incident angle at 67 kHz frequency. Assuming that killer whales share similar morphology structure with the bottlenose dolphin, we extrapolated the TS of an adult killer whale 7.5 m in length at 67 kHz frequency with -8 dB at broadside aspect and -28 dB at tail side. The backscattering data from three Southern Resident killer whales were analyzed to obtain the TS measurement. These data were collected at Lime Kiln State Park using a split-beam system deployed from a boat. The TS of the killer whale at higher frequency (200 kHz) was estimated based on a three-layer model for plane wave reflection from the lung of the whale. The TS data of killer whales were in good agreement with our model. In this paper, we also discuss and explain possible causes for measurement estimation error.

  18. Optogenetic in vivo cell manipulation in KillerRed-expressing zebrafish transgenics

    Shidlovsky Konstantin; Sek Jun-Yan; Mamedov Ilgar Z; Poon Kar-Lai; Chudakov Dmitry M; Teh Cathleen; Lukyanov Sergey; Korzh Vladimir

    2010-01-01

    Abstract Background KillerRed (KR) is a novel photosensitizer that efficiently generates reactive oxygen species (ROS) in KR-expressing cells upon intense green or white light illumination in vitro, resulting in damage to their plasma membrane and cell death. Results We report an in vivo modification of this technique using a fluorescent microscope and membrane-tagged KR (mem-KR)-expressing transgenic zebrafish. We generated several stable zebrafish Tol2 transposon-mediated enhancer-trap (ET)...

  19. Population dynamics and distribution of northern Norwegian killer whales in relation to wintering herring

    Kuningas, Sanna

    2014-01-01

    The northern Norwegian killer whale (Orcinus orca) is an important predator but little is known about its population dynamics, particular in response to changes in its main prey, the highly dynamic Norwegian spring spawning (NSS) herring (Clupea harengus). The main aims of this thesis were to estimate killer whale population parameters, to explore the future viability of the population, and to explore the response of this predator to changes in distribution and abundance of its main prey over...

  20. Competing conservation objectives for predators and prey: estimating killer whale prey requirements for Chinook salmon.

    Rob Williams

    Full Text Available Ecosystem-based management (EBM of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca and their primary prey, Chinook salmon (Oncorhynchus tshawytscha. Both species have at-risk conservation status and transboundary (Canada-US ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of

  1. Construction of Killer Industrial Yeast Saccharomyces Cerevisiae Hau-1 and its Fermentation Performance

    Bajaj, Bijender K.; S Sharma

    2010-01-01

    Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of the desirable fermentation characteristics like fast growth and fermentation rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to ferment at elevated temperatures etc. However, this yeast was found to be sensitive against the killer strains of Saccharomyces cerevisiae. In the present study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by protoplast fusion with Saccha...

  2. Construction of killer industrial yeast Saccharomyces cerevisiae HAU-1 and its fermentation performance

    Bajaj, Bijender K.; S Sharma

    2010-01-01

    Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of the desirable fermentation characteristics like fast growth and fermentation rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to ferment at elevated temperatures etc. However, this yeast was found to be sensitive against the killer strains of Saccharomyces cerevisiae. In the present study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by protoplast fusion with Saccha...

  3. Aggressive natural killer-cell leukemia: Classical presentation of a rare disease

    Priya M Jacob

    2014-01-01

    Full Text Available Aggressive natural killer-cell leukaemia is a rare aggressive form of natural killer-cell neoplasm. We report a case of a 40-year-old male who presented with jaundice, raised blood counts,generalised lymphadenopathy and hepatosplenomegaly. The diagnosis was established by flow cytometric analysis of bone marrow aspirate. The patient, however, succumbed to his illness within 2 weeks of starting chemotherapy. To the best of our knowledge, this is the third reported case from India.

  4. Understanding Patient Management: the Need for Medication Adherence and Persistence

    2008-01-01

    Poor patient adherence to medication is one of the major factors contributing to poor disease control, in particular in asymptomatic chronic diseases like hypertension and dyslipidaemia. The physical and economic burden on patients and the health care system as a result of non-adherence is great. It is estimated that poor adherence to hypertension medication accounts for as many as 7.1 million preventable deaths annually. Hence recognising and identifying non-adherence is the first step to ad...

  5. Predictors of Low Clopidogrel Adherence Following Percutaneous Coronary Intervention

    Muntner, Paul; Mann, Devin M.; Woodward, Mark; Choi, James W.; Stoler, Robert C; Shimbo, Daichi; Farkouh, Michael E.; Kim, Michael C.

    2011-01-01

    Few data are available on factors associated with low adherence or early clopidogrel discontinuation following percutaneous coronary intervention (PCI). Patients (n=284) were evaluated prior to hospital discharge following PCI to identify factors associated with low adherence to clopidogrel 30 days later. Pre-PCI adherence to daily medications was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low, medium, or high (scores

  6. Estimates of adherence to treatment of vivax malaria

    Almeida, Eduardo D; Rodrigues, Luiz Carlos S; Vieira, José Luiz F

    2014-01-01

    Background The relation between therapeutic failure and non-adherence to treatment of malaria has been clearly established. Several measures have been used to estimate adherence to Plasmodium vivax therapy, but few protocols have been validated to ensure reliability of the estimates of adherence. The objective of this study was to validate a five-item-reported-questionnaire derived from original Morisky four-item scale to estimate adherence to P. vivax malaria therapy. Methods A five-item-rep...

  7. Antiretroviral Therapy Adherence Among Transgender Women Living with HIV

    Sevelius, Jae M.; Carrico, Adam; Johnson, Mallory O.

    2010-01-01

    Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral treatment (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence including depression, adherence self-efficacy, patient perceptio...

  8. Supporting patients : pharmacy based interventions to improve medication adherence

    Kooij, M. J.

    2015-01-01

    For many patients it is not easy to adhere to the agreed treatment with medication. Adherence has been defined as “the extent to which a person’s behaviour - taking medication - corresponds with agreed recommendations from a health care provider”. Numerous factors influence this taking behaviour and non-adherence must not be seen as the patients’ problem only. Health care providers, including pharmacists, should support patients to adhere. The overall aim of this thesis was to evaluate interv...

  9. Adherence to Diet in Youth with Type 1 Diabetes

    Patton, Susana R.

    2011-01-01

    This paper reviewed current findings on dietary adherence in youth with type 1 diabetes mellitus (T1DM), discussed factors predicting dietary adherence, and presented directions for future research. The search terms were: type 1 diabetes mellitus; youth (0-22 years); diet; dietary adherence; nutrition; dietary intake; obesity; and complications. The studies involved youth with T1DM, presented dietary adherence data specifically, and/or described usual dietary patterns in youth. Articles that ...

  10. Pollen Killer Gene S35 Function Requires Interaction with an Activator That Maps Close to S24, Another Pollen Killer Gene in Rice

    Takahiko Kubo

    2016-05-01

    Full Text Available Pollen killer genes disable noncarrier pollens, and are responsible for male sterility and segregation distortion in hybrid populations of distantly related plant species. The genetic networks and the molecular mechanisms underlying the pollen killer system remain largely unknown. Two pollen killer genes, S24 and S35, have been found in an intersubspecific cross of Oryza sativa ssp. indica and japonica. The effect of S24 is counteracted by an unlinked locus EFS. Additionally, S35 has been proposed to interact with S24 to induce pollen sterility. These genetic interactions are suggestive of a single S24-centric genetic pathway (EFS–S24–S35 for the pollen killer system. To examine this hypothetical genetic pathway, the S35 and the S24 regions were further characterized and genetically dissected in this study. Our results indicated that S35 causes pollen sterility independently of both the EFS and S24 genes, but is dependent on a novel gene close to the S24 locus, named incentive for killing pollen (INK. We confirmed the phenotypic effect of the INK gene separately from the S24 gene, and identified the INK locus within an interval of less than 0.6 Mb on rice chromosome 5. This study characterized the genetic effect of the two independent genetic pathways of INK–S35 and EFS–S24 in indica–japonica hybrid progeny. Our results provide clear evidence that hybrid male sterility in rice is caused by several pollen killer networks with multiple factors positively and negatively regulating pollen killer genes.