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Sample records for lethally irradiated animals

  1. Skin allografts in lethally irradiated animals repopulated with syngeneic hemopoietic cells

    SciTech Connect

    Schwadron, R.B.

    1983-01-01

    Total body irradiation and repopulation with syngeneic hemopoietic cells can be used to induce tolerance to major histocompatibility complex (MHC) mismatched heart and kidney grafts in rats and mice. However, this protocol does not work for MHC mismatched skin grafts in rats or mice. Furthermore, LEW rats that accept WF cardiac allografts after irradiation and repopulation reject subsequent WF skin grafts. Treatment of skin allograft donors with methotrexate prior to grafting onto irradiated and reconstituted mice resulted in doubling of the mean survival time. Analysis of which antigens provoked skin graft rejection by irradiation and reconstituted animals revealed the importance of I region antigens. Cardiac allograft acceptance by irradiated and reconstituted animals is mediated by suppressor cells found in the spleen. Adoptively tolerant LEW rats accepted WF skin grafts in 50% of grafted animals. Analysis of this phenomenon revealed that the adoptive transfer procedure itself was important in achieving skin allograft acceptance by these animals. In general, it seems that the lack of ability of irradiated and reconstituted animals to accept fully MHC disparate skin grafts results from the inability of these animals to suppress lymph node effector cells against I region antigen seen on highly immunogenic allogeneic Langerhans cells in the skin.

  2. Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

    PubMed Central

    Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

    2015-01-01

    Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

  3. Necrostatin-1 rescues mice from lethal irradiation.

    PubMed

    Huang, Zhentai; Epperly, Michael; Watkins, Simon C; Greenberger, Joel S; Kagan, Valerian E; Bayır, Hülya

    2016-04-01

    There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFα levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L-tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. PMID:26802452

  4. Podophyllum hexandrum-Mediated Survival Protection and Restoration of Other Cellular Injuries in Lethally Irradiated Mice.

    PubMed

    Sankhwar, Sanghmitra; Gupta, Manju Lata; Gupta, Vanita; Verma, Savita; Suri, Krishna Avtar; Devi, Memita; Sharma, Punita; Khan, Ehsan Ahmed; Alam, M Sarwar

    2011-01-01

    This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

  5. Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis.

    PubMed

    Hofer, M; Pospísil, M; Tkadlecek, L; Viklická, S; Pipalová, I; Holá, J

    1992-01-01

    An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation.

  6. Effects of feeding lactobacillus GG on lethal irradiation in mice

    SciTech Connect

    Dong, M.Y.; Chang, T.W.; Gorbach, S.L.

    1987-05-01

    Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls.

  7. Protection of mouse jejunum against lethal irradiation by Podophyllum hexandrum.

    PubMed

    Salin, C A; Samanta, N; Goel, H C

    2001-11-01

    Radiation induced gastrointestinal damage occurs due to the destruction of the clonogenic crypt cells and eventual depopulation and denudation of the villi. P. hexandrum, a plant, known for its antitumour activity, has been shown to protect the mice against whole body lethal (10 Gy) irradiation. Present study was undertaken to investigate the radioprotective effect of P. hexandrum on jejunal villi cells, crypt cells, their proliferative capacity and mitigation of apoptosis. In an in vivo micro colony survival assay, pre-irradiation administration of P. hexandrum (-2 h) increased the number of surviving crypts in the jejunum by a factor of 3.0 (P < 0.05) and villi cellularity by 2.7 (P < 0.05) fold in comparison to irradiated control. Pre-irradiation administration of P. hexandrum reduced the incidence of apoptotic bodies in the crypts (P < 0.05) in a time dependent manner and depicted a mitotic arrest till the 24 h. However, after 84 h the percentage of mitosis was observed to be nearly similar to that of unirradiated control. This study suggests that arrest of cell division may help in protecting the clonogenic cells against radiation. It would be interesting to investigate further the role of P hexandrum in influencing various cell cycle regulators like bcl-2, TGF-beta, Cyclin-E etc.

  8. Oral Interleukin 11 as a Countermeasure to Lethal Total-Body Irradiation in a Murine Model

    PubMed Central

    Burnett, Alexander F.; Biju, Prabath G.; Lui, Huanli; Hauer-Jensen, Martin

    2014-01-01

    Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total-body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure. PMID:24219324

  9. Protective efficacy of semi purified fraction of high altitude podophyllum hexandrum rhizomes in lethally irradiated Swiss albino mice.

    PubMed

    Gupta, M L; Tyagi, S; Flora, S J S; Agrawala, P K; Choudhary, P; Puri, S C; Sharma, A; Devi, M; Haksar, A; Qazi, G N; Tripathi, R P

    2007-05-30

    A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was evaluated for its radioprotective efficacy against lethal gamma-irradiation (10 Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50 of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively. Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006 rendered > 90% survival in lethally irradiated mice. The dose reduction factor was calculated to be 1.62 considering survival as the end point. REC-2006 treatment marked in significant increase in endogenous spleen colony forming units. In REC-2006 treated group, super oxide dismutase activity was increased significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and highly promising to achieve significant radioprotection against lethal radiation. Further purification and identification of active molecules and their efficacy studies in higher animals therefore demand attention.

  10. Prevention of GVHD by modulation of rat bone marrow with UV-B irradiation. II. Kinetics of migration of UV-B-irradiated bone marrow cells in naive and lethally irradiated rats

    SciTech Connect

    Oluwole, S.F.; Engelstad, K.; Hardy, M.A. )

    1990-06-01

    UV-B irradiation (700 J/m2) of bone marrow (BM) cells prior to transplantation into lethally gamma-irradiated (1050 rad) allogeneic rats prevents the development of GVHD and results in a stable mixed lymphohematopoietic chimerism. To better understand the underlying mechanisms of the development of stable radiation chimeras in this model, this study was designed to examine whether the dose (700 J/m2) of UV-B irradiation used for the modulation of the BM inoculum would affect the homing pattern of radiolabeled BM cells compared to that of thoracic duct lymphocytes (TDL) in the naive and lethally irradiated recipients. The results showed that intravenously administered, 111Indium-oxine-labeled, unmodified TDL home specifically to the spleen, lymph nodes, and BM compartments with a subsequent recirculation of a large number of cells from the spleen to the lymph nodes. In contrast, radiolabeled, unmodified BM cells migrate specifically to the spleen, liver, and BM with the lymph nodes, thymus, and nonlymphoid organs containing very little amounts of radioactivity. The stable concentrations of radioactivity in the lymphoid and nonlymphoid compartments between 3 and 72 hr after injection suggest that BM cells, unlike TDL, do not recirculate. The migration pattern of BM cells in the naive recipient was not significantly different from that seen in lethally irradiated animals except for the higher concentration of radioactivity in the spleen and BM of irradiated animals compared to that seen in naive recipients. The similarity of tissue localization of BM cells in naive or in irradiated syngeneic recipients to that of allogeneic recipients suggests that the homing of BM cells is not MHC restricted.

  11. Suspended animation-like state protects mice from lethal hypoxia.

    PubMed

    Blackstone, Eric; Roth, Mark B

    2007-04-01

    Joseph Priestley observed the high burn rate of candles in pure oxygen and wondered if people would "live out too fast" if we were in the same environment. We hypothesize that sulfide, a natural reducer of oxygen that is made in many cell types, acts as a buffer to prevent unrestricted oxygen consumption. To test this, we administered sulfide in the form of hydrogen sulfide (H2S) to mice (Mus musculus). As we have previously shown, H2S decreases the metabolic rate of mice by approximately 90% and induces a suspended animation-like state. Mice cannot survive for longer than 20 min when exposed to 5% oxygen. However, if mice are first put into a suspended animation-like state by a 20-min pretreatment with H2S and then are exposed to low oxygen, they can survive for more than 6.5 h in 5% oxygen with no apparent detrimental effects. In addition, if mice are exposed to a 20-min pretreatment with H2S followed by 1 h at 5% oxygen, they can then survive for several hours at oxygen tensions as low as 3%. We hypothesize that prior exposure to H2S reduces oxygen demand, therefore making it possible for the mice to survive with low oxygen supply. These results suggest that H2S may be useful to prevent damage associated with hypoxia. PMID:17414418

  12. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity after Lethal Total Body Irradiation

    PubMed Central

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

    2012-01-01

    Purpose To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for five consecutive days starting within one hour post exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied using an in vitro culture system. Results IGF-1 protected 8 out of 20 mice (40%) from lethal irradiation while only 2 out of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for five days. Positive effects were noted even when the initiation of treatment was delayed up to six hours post irradiation. Compared with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red cells in peripheral blood, total cell numbers as well as hematopoietic stem cells and progenitors in the bone marrow when measured at day 14 post-irradiation. IGF-1 protected both hematopoietic stem cells and progenitors from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of non-irradiated and irradiated hematopoietic progenitors. Conclusions IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitors. PMID:23021438

  13. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  14. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

    SciTech Connect

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

    2013-03-15

    Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

  15. Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens.

    PubMed

    Lydyard, P M; Ivanvi, J

    1975-08-01

    Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft. PMID:241144

  16. A novel challenge test incorporating irradiation (60Co) of compost sub-samples to validate thermal lethality towards pathogenic bacteria.

    PubMed

    Moore, John E; Watabe, Miyuki; Stewart, Andrew; Cherie Millar, B; Rao, Juluri R

    2009-01-01

    Maturing compost heaps normally attaining temperatures ranging from 55 to 65 degrees C is generally regarded to conform to recommended biological risks and sanitation standards for composts stipulated by either EU or US-EPA. Composted products derived from animal sources are further required by EU biohazard safety regulatory legislation that such composts either attain 70 degrees C for over 3h during maturation or via treatment at 70 degrees C for 1h before being considered for dispensation on land. The setting of the upper limit of thermal lethality at 70 degrees C/1h for achieving biosecurity of the animal waste composted products (e.g. pelleted fertilizer formulations) is not properly substantiated by specific validation tests, comprising a 'wipe-out' step (usually via autoclaving) followed by inoculation of a prescribed bacterium, exposure to 70 degrees C/1h and the lethality determined. Pelleted formulations of composts are not amenable for wet methods (autoclaving) for wipe-out sterilization step as this is detrimental to the pellet and compromises sample integrity. This study describes a laboratory method involving the employment of ((60)Co) irradiation 'wipe-out' step to: (a) compost sub-samples drawn from compost formulation heaps and (b) pelleted products derived from composted animal products while determining the thermal lethality of a given time/temperature (70 degrees C/1h) treatment process and by challenging the irradiated sample (not just with one bacterium but), out with 10 potential food-poisoning organisms from the bacterial genera (Campylobacter, Escherichia, Listeria, Salmonella, Yersinia) frequently detected in pig and poultry farm wastes. This challenge test on compost sub-samples can be a useful intervention ploy for 'inspection and validation' technique for composters during the compost maturity process, whose attainment of temperatures of 55-65 degrees C is presumed sufficient for attainment of sanitation. Stringent measures are further

  17. MicroRT - Small animal conformal irradiator

    SciTech Connect

    Stojadinovic, S.; Low, D. A.; Hope, A. J.; Vicic, M.; Deasy, J. O.; Cui, J.; Khullar, D.; Parikh, P. J.; Malinowski, K. T.; Izaguirre, E. W.; Mutic, S.; Grigsby, P. W.

    2007-12-15

    A novel small animal conformal radiation therapy system has been designed and prototyped: MicroRT. The microRT system integrates multimodality imaging, radiation treatment planning, and conformal radiation therapy that utilizes a clinical {sup 192}Ir isotope high dose rate source as the radiation source (teletherapy). A multiparameter dose calculation algorithm based on Monte Carlo dose distribution simulations is used to efficiently and accurately calculate doses for treatment planning purposes. A series of precisely machined tungsten collimators mounted onto a cylindrical collimator assembly is used to provide the radiation beam portals. The current design allows a source-to-target distance range of 1-8 cm at four beam angles: 0 deg. (beam oriented down), 90 deg., 180 deg., and 270 deg. The animal is anesthetized and placed in an immobilization device with built-in fiducial markers and scanned using a computed tomography, magnetic resonance, or positron emission tomography scanner prior to irradiation. Treatment plans using up to four beam orientations are created utilizing a custom treatment planning system--microRTP. A three-axis computer-controlled stage that supports and accurately positions the animals is programmed to place the animal relative to the radiation beams according to the microRTP plan. The microRT system positioning accuracy was found to be submillimeter. The radiation source is guided through one of four catheter channels and placed in line with the tungsten collimators to deliver the conformal radiation treatment. The microRT hardware specifications, the accuracy of the treatment planning and positioning systems, and some typical procedures for radiobiological experiments that can be performed with the microRT device are presented.

  18. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    PubMed

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-08-12

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  19. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    PubMed Central

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID:26274957

  20. Intrinsic resistance to the lethal effects of x-irradiation in insect and arachnid cells

    PubMed Central

    Koval, Thomas M.

    1983-01-01

    Twelve cell lines representing 10 genera of three orders (Diptera, Lepidoptera, and Orthoptera) of the class Insecta and one cell line (Acarina) from the class Arachnida were examined to discern their sensitivity to the lethal effects of x-irradiation. Radiosensitivity was measured by a combination of colony formation and population growth curve techniques. Each of these arthropod cell lines is significantly more radioresistant than mammalian cells, though the degree of resistance varies greatly with order. Dipteran cells are 3 to 9 times and lepidopteran cells 52 to 104 times more radioresistant than mammalian cells. Orthopteran and acarine cells are intermediate in radiosensitivity between dipteran and lepidopteran cells. These cells, especially the lepidopteran, should be valuable in determining the molecular nature of repair mechanisms that result in resistance to ionizing radiation. PMID:16593348

  1. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    PubMed

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

  2. Establishment of a mouse model of 70% lethal dose by total-body irradiation

    PubMed Central

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun

    2016-01-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  3. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    PubMed

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  4. The effects of sub-lethal UV-C irradiation on growth and cell integrity of cyanobacteria and green algae.

    PubMed

    Tao, Yi; Zhang, Xihui; Au, Doris W T; Mao, Xianzhong; Yuan, Kan

    2010-01-01

    The effects of UV-C irradiation on algal growth and cell integrity were investigated to develop a potential method for preventing cyanobacterial blooms. The toxic cyanobacterium Microcystis aeruginosa and three common freshwater green algae Chlorella ellipsoidea, Chlorella vulgaris, and Scenedesmus quadricanda were exposed to UV-C irradiation at 0-200mJcm(-2) and subsequently incubated for 9-15 d under normal culture conditions. Cell density and cell integrity were assessed using flow cytometry. The results suggested that UV-C irradiation at 20-200mJcm(-2) can suppress M. aeruginosa growth for 3-13 d in a dose-dependent manner. UV-C irradiation at 20 and 50mJcm(-2) is sub-lethal to M. aeruginosa cells as over 80% of the exposed cells remained intact. However, UV-C irradiation at 100 and 200mJcm(-2) induced severe cell disintegration in more than 70% of the irradiated cells. Neither significant suppression nor disintegration effects on green algae were observed for UV-C irradiation at 20-200mJcm(-2) in this study. Taken together, the sensitivity of M. aeruginosa to UV-C irradiation was significantly higher than that of the non-toxic C. ellipsoidea, C. vulgaris, and S. quadricauda, suggesting the potential application of sub-lethal UV-C irradiation for M. aeruginosa bloom control with a predictable low ecological risk. PMID:20005556

  5. Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

    SciTech Connect

    Afifi, M.S.H.

    1985-01-01

    The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion.

  6. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

    PubMed

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

  7. Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality

    PubMed Central

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure. PMID:25651298

  8. Short-term injection of antiapoptotic cytokine combinations soon after lethal gamma -irradiation promotes survival.

    PubMed

    Hérodin, Francis; Bourin, Philippe; Mayol, Jean-François; Lataillade, Jean-Jacques; Drouet, Michel

    2003-04-01

    Recovery from radiation-induced (RI) myelosuppression depends on hematopoietic stem and progenitor cell survival and the active proliferation/differentiation process, which requires early cytokine support. Single cytokine or late-acting growth factor therapy has proved to be inefficient in ensuring reconstitution after severe RI damage. This work was aimed at evaluating the in vivo survival effect of combinations of early-acting cytokines whose antiapoptotic activity has been demonstrated in vitro: stem cell factor (SCF [S]), FMS-like tyrosine kinase 3 ligand (FLT-3 ligand [F]), thrombopoietin (TPO [T]), interleukin-3 (IL-3 [3]), and stromal derived factor-1 (SDF-1). B6D2F1 mice underwent total body irradiation at 8 Gy cesium Cs 137 gamma radiation (ie, lethal dose 90% at 30 days) and were treated soon after irradiation, at 2 hours and at 24 hours, with recombinant murine cytokines, each given intraperitoneally at 50 microg/kg per injection. All treatments induced 30-day survival rates significantly higher than control (survival rate, 8.3%). 4F (SFT3) and 5F (4F + SDF-1) were the most efficient combinations (81.2% and 87.5%, respectively), which was better than 3F (SFT, 50%), TPO alone (58.3%), and SDF-1 alone (29.2%) and also better than 4F given at 10 microg/kg per injection (4F10, 45.8%) or as a 50 microg/kg single injection at 2 hours (4Fs, 62.5%). Despite delayed death occurring mainly from day 150 on and possible long-term hematopoiesis impairment, half the 30-day protective effects of 4F and 5F were preserved at 300 days. Our results show that short- and long-term survival after irradiation depends on appropriate multiple cytokine combinations and at optimal concentrations. The proposal is made that an emergency cytokine regimen could be applied to nuclear accident victims as part of longer cytokine treatment, cell therapy, or both.

  9. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

    SciTech Connect

    Hartnett, L.C.

    1983-01-01

    Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.

  10. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  11. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    SciTech Connect

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. )

    1990-10-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

  12. Administration of an immunomodulatory azaspirane, SK F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice

    SciTech Connect

    King, A.G.; Badger, A.M. )

    1991-08-01

    The immunomodulatory azaspirane SK F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be null cells, that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because the authors hypothesized that the induction of SC was associated with enhanced hematopoiesis, they sought to determine the hematopoietic potential of SK F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in their studies. They demonstrate here that administration of SK F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In their experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.

  13. Genetic studies: dominant lethal study, sex linked recessive lethal, ames mutagenicity, and heritable translocation test of thermal processed, frozen, electron irradiated, and gamma irradiated chicken. Final report Jun 76-Aug 83

    SciTech Connect

    Sullivan, D.; Lusskin, R.M.; Thomson, G.M.; Kuzdas, C.D.; Ronning, D.C.

    1983-01-01

    Four samples of chicken meat identified as the frozen control, thermally processed, gamma sterilized (5.9 Mrad), and electron sterilized (5.9 MeV), along with negative and positive controls, were evaluated for genetic activity. The samples were evaluated for ability to induce dominant lethal mutations in spermatid and spermatozoan stages of spermatogenesis in mice fed 35 percent chicken meat. The test meat samples were not observed to have an effect on the incidence of the dominant lethal mutations. However, the positive control failed to give a positive response. The meat samples were investigated for mutagenic activity employing Drosophila melanogaster in the sex linked recessive lethal test. The samples were determined to be nonmutagenic in this test and the positive control gave a significant response. Reduced production of offspring in cultures of Drosophila reared on gamma irradiated chicken which could not be overcome by the addition of vitamins was observed. Pre-incubation tests with and without added mutagens revealed that in no case was a positive result observed in the Ames test from chicken meat without an added mutagen. The manner in which chicken meat was processed had no effect upon the response to the Ames test. A heritable translocation test in mice failed to reveal any cytological evidence of translocation heterozygosity in any of the chicken-containing diets.

  14. THE PROLONGED GASTROINTESTINAL SYNDROME IN RHESUS MACAQUES: THE RELATIONSHIP BETWEEN GASTROINTESTINAL, HEMATOPOIETIC, AND DELAYED MULTI-ORGAN SEQUELAE FOLLOWING ACUTE, POTENTIALLY LETHAL, PARTIAL-BODY IRRADIATION

    PubMed Central

    MacVittie, Thomas J.; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M.

    2014-01-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  15. Successful semiallogeneic and allogeneic bone marrow reconstitution of lethally irradiated adult mice mediated by neonatal spleen cells

    SciTech Connect

    LaFace, D.M.; Peck, A.B.

    1987-11-01

    Spleens of fetal/newborn mice less than 3-4 days of age contain a naturally occurring cell population capable of suppressing T-dependent and T-independent immune responses of third-party adult cells both in vitro and in vivo. We have utilized newborn spleen cells to prevent acute graft-versus-host (GVH) disease in lethally irradiated adult hosts reconstituted with semiallogeneic or even allogeneic bone marrow cells. Pretreatment of reconstituting cell populations with newborn spleen cells reduced the incidence of GVH disease from 100% to 20% in semiallogeneic and from 100% to 40% in allogeneic combinations. Long-term-surviving reconstituted hosts proved immunologically unresponsive to both donor and host histocompatibility antigens, yet possessed a fully chimeric lymphoid system responsive to T and B cell mitogens, as well as unrelated third-party alloantigens.

  16. Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host

    SciTech Connect

    Pierpaoli, W.; Dall'Ara, A.; Yi, C.X.; Neri, P.; Santucci, A.; Choay, J. )

    1991-04-15

    Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This 'bio-active' fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.

  17. Why are Wischnewski spots not always present in lethal hypothermia? The results of testing a stress-reduced animal model.

    PubMed

    Bright, Fiona; Winskog, Calle; Walker, Melissa; Byard, Roger W

    2013-08-01

    Hypothermic fatalities in humans are characterized by a range of often subtle pathological findings that typically include superficial erosive gastritis (Wischnewski spots). Experimental studies have been successfully performed using animal models to replicate this finding, however study animals have inevitably been subjected to a variety of additional stressors including food deprivation, restraint and partial immersion in water while conscious. As it is recognised that stress on its own may cause superficial erosive gastritis, a model has been developed to enable the study of the effects of hypothermia in isolation. 42 Sprague-Dawley rats were allowed free social contact and were fed and watered ad libitum prior to being anaesthetized with isoflurane. Once unconscious, rats were placed on drape cloth covering metal mesh platforms in a styrofoam box packed with ice. The apparatus enabled both maintenance of a specific low temperature (26 °C) in 14 animals, and continued reduction of core temperatures in the remaining 28 (who all died of hypothermia under anaesthesia). Examination of the gastric mucosa in both groups macroscopically and microscopically failed to demonstrate typical Wischnewski spots in any of the 42 animals. Thus, in this model, death from hypothermia occurred without the development of these lesions. These results suggest that stress may be a significant effect modifier in the development of Wischnewski spots in lethal hypothermia.

  18. Why are Wischnewski spots not always present in lethal hypothermia? The results of testing a stress-reduced animal model.

    PubMed

    Bright, Fiona; Winskog, Calle; Walker, Melissa; Byard, Roger W

    2013-08-01

    Hypothermic fatalities in humans are characterized by a range of often subtle pathological findings that typically include superficial erosive gastritis (Wischnewski spots). Experimental studies have been successfully performed using animal models to replicate this finding, however study animals have inevitably been subjected to a variety of additional stressors including food deprivation, restraint and partial immersion in water while conscious. As it is recognised that stress on its own may cause superficial erosive gastritis, a model has been developed to enable the study of the effects of hypothermia in isolation. 42 Sprague-Dawley rats were allowed free social contact and were fed and watered ad libitum prior to being anaesthetized with isoflurane. Once unconscious, rats were placed on drape cloth covering metal mesh platforms in a styrofoam box packed with ice. The apparatus enabled both maintenance of a specific low temperature (26 °C) in 14 animals, and continued reduction of core temperatures in the remaining 28 (who all died of hypothermia under anaesthesia). Examination of the gastric mucosa in both groups macroscopically and microscopically failed to demonstrate typical Wischnewski spots in any of the 42 animals. Thus, in this model, death from hypothermia occurred without the development of these lesions. These results suggest that stress may be a significant effect modifier in the development of Wischnewski spots in lethal hypothermia. PMID:23910881

  19. Integration of optical imaging with a small animal irradiator

    SciTech Connect

    Weersink, Robert A.; Ansell, Steve; Wang, An; Wilson, Graham; Shah, Duoaud; Lindsay, Patricia E.; Jaffray, David A.

    2014-10-15

    Purpose: The authors describe the integration of optical imaging with a targeted small animal irradiator device, focusing on design, instrumentation, 2D to 3D image registration, 2D targeting, and the accuracy of recovering and mapping the optical signal to a 3D surface generated from the cone-beam computed tomography (CBCT) imaging. The integration of optical imaging will improve targeting of the radiation treatment and offer longitudinal tracking of tumor response of small animal models treated using the system. Methods: The existing image-guided small animal irradiator consists of a variable kilovolt (peak) x-ray tube mounted opposite an aSi flat panel detector, both mounted on a c-arm gantry. The tube is used for both CBCT imaging and targeted irradiation. The optical component employs a CCD camera perpendicular to the x-ray treatment/imaging axis with a computer controlled filter for spectral decomposition. Multiple optical images can be acquired at any angle as the gantry rotates. The optical to CBCT registration, which uses a standard pinhole camera model, was modeled and tested using phantoms with markers visible in both optical and CBCT images. Optically guided 2D targeting in the anterior/posterior direction was tested on an anthropomorphic mouse phantom with embedded light sources. The accuracy of the mapping of optical signal to the CBCT surface was tested using the same mouse phantom. A surface mesh of the phantom was generated based on the CBCT image and optical intensities projected onto the surface. The measured surface intensity was compared to calculated surface for a point source at the actual source position. The point-source position was also optimized to provide the closest match between measured and calculated intensities, and the distance between the optimized and actual source positions was then calculated. This process was repeated for multiple wavelengths and sources. Results: The optical to CBCT registration error was 0.8 mm. Two

  20. Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

    PubMed

    Kameneva, Marina V; Wu, Zhongjun J; Uraysh, Arkady; Repko, Brandon; Litwak, Kenneth N; Billiar, Timothy R; Fink, Mitchell P; Simmons, Richard L; Griffith, Bartley P; Borovetz, Harvey S

    2004-01-01

    Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

  1. Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.

    PubMed

    Tiberghien, P; Laithier, V; Mabed, M; Racadot, E; Reynolds, C W; Angonin, R; Loumi, R; Pavy, J J; Cahn, J Y; Noir, A

    1993-04-01

    Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment. PMID:8461477

  2. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    PubMed

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  3. An anti-apoptotic peptide improves survival in lethal total body irradiation

    SciTech Connect

    McDunn, Jonathan E.; Muenzer, Jared T.; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C.; Davis, Christopher G.; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S.

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 {mu}M) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  4. Dosimetry Formalism and Implementation of a Homogenous Irradiation Protocol to Improve the Accuracy of Small Animal Whole-Body Irradiation Using a 137Cs Irradiator.

    PubMed

    Brodin, N Patrik; Chen, Yong; Yaparpalvi, Ravindra; Guha, Chandan; Tomé, Wolfgang A

    2016-02-01

    Shielded Cs irradiators are routinely used in pre-clinical radiation research to perform in vitro or in vivo investigations. Without appropriate dosimetry and irradiation protocols in place, there can be large uncertainty in the delivered dose of radiation between irradiated subjects that could lead to inaccurate and possibly misleading results. Here, a dosimetric evaluation of the JL Shepard Mark I-68A Cs irradiator and an irradiation technique for whole-body irradiation of small animals that allows one to limit the between subject variation in delivered dose to ±3% are provided. Mathematical simulation techniques and Gafchromic EBT film were used to describe the region within the irradiation cavity with homogeneous dose distribution (100% ± 5%), the dosimetric impact of varying source-to-subject distance, and the variation in attenuation thickness due to turntable rotation. Furthermore, an irradiation protocol and dosimetry formalism that allows calculation of irradiation time for whole-body irradiation of small animals is proposed that is designed to ensure a more consistent dose delivery between irradiated subjects. To compare this protocol with the conventional irradiation protocol suggested by the vendor, high-resolution film dosimetry measurements evaluating the dose difference between irradiation subjects and the dose distribution throughout subjects was performed using phantoms resembling small animals. Based on these results, there can be considerable variation in the delivered dose of > ± 5% using the conventional irradiation protocol for whole-body irradiation doses below 5 Gy. Using the proposed irradiation protocol this variability can be reduced to within ±3% and the dosimetry formalism allows for more accurate calculation of the irradiation time in relation to the intended prescription dose. PMID:26710162

  5. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.

    PubMed

    Li, Jianzhong; Xu, Jing; Lu, Yiming; Qiu, Lei; Xu, Weiheng; Lu, Bin; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2016-05-17

    Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  6. Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and protects mice from lethal total body irradiation

    SciTech Connect

    Constine, L.S.; Harwell, S.; Keng, P.; Lee, F.; Rubin, P.; Siemann, D. )

    1991-03-01

    Interleukin 1 alpha (IL-1) is a polypeptide/glycoprotein growth factor with multiple functions including the modulation of hematopoietic cell proliferation and differentiation. In vivo studies were performed with C57BL/6J mice injected with 0, 0.2, or 2.0 micrograms of IL-1 24 hr before or after lethal total body irradiation (TBI) (9.5 Gy). More mice in the groups administered IL-1 before TBI survived (90% of the 2.0 micrograms group) than those treated 2 or 24 hr after TBI, which was still slightly superior to the uninjected group, which all died within 15 days (p = .0001). Proliferation of bone marrow granulocyte/macrophage colonies following split dose TBI was also greatest for mouse groups treated with IL-1 prior to TBI. These experiments support data from other investigators that IL-1 stimulation of BM is related to IL-1 timing with respect to TBI. Stimulation of hemopoiesis was also assessed in terms of changes in peripheral blood and BM cell numbers and cell cycle kinetics using an electronic particle counter and flow cytometric techniques. Mice injected with 2 micrograms of IL-1 showed an initial decline (at 3-6 hr) and then a selective proliferation (24-48 hr) of early and more committed progenitor cells to 125% and 200% of control values, respectively. Peripheral blood counts rose accordingly. Cells in S and G2/M phases increased over 10 hr and then declined in number. It thus appeared that some synchronization of cell cycling occurred, which might place cells in a more radioresistant phase of the cell cycle. The glutathione (GSH) content and synthesis in BM cells were measured by isocratic paired-ion high performance liquid chromatography and 35S-labelled cysteine incorporation into the GSH tripeptide. An increase in cellular GSH content and synthesis was demonstrated following IL-1 which lasted 24 hr.

  7. Lethal effects of short-wavelength visible light on insects

    NASA Astrophysics Data System (ADS)

    Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

    2014-12-01

    We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

  8. Lethal effects of short-wavelength visible light on insects.

    PubMed

    Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

    2014-12-09

    We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

  9. Role of marrow architecture and stromal cells in the recovery process of aplastic marrow of lethally irradiated rats parabiosed with healthy litter mates

    SciTech Connect

    Hayashi, K.; Kagawa, K.; Awai, M.; Irino, S.

    1986-01-01

    Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty aplastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the aplastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells.

  10. Evidence that repair and expression of potentially lethal damage cause the variations in cell survival after x irradiation observed through the cell cycle in Ehrlich ascites tumor cells

    SciTech Connect

    Iliakis, G.; Nuesse, M.

    1983-07-01

    The survival of synchronously growing Ehrlich ascites tumor cells (EAT cells) was measured after x irradiation in various stages of the cell cycle. Cells at the beginning of S or in G2 + M phase showed a high level of killing, whereas cells irradiated in G1 or in the middle of S phase were more resistant. These changes resulted from a change in the survival curve shoulder width (D/sub q/) as cells passed through the cell cycle, and the mean lethal dose (D/sub 0/) remained practically unchanged (0.8 +- 0.05 Gy). When synchronization of the cell population was further sharpened using nocodazole, exponential survival curves were obtained at the beginning of S phase and at mitosis with a D/sub 0/ = 0.8 Gy. When cells (in all stages) were incubated in balanced salt solution for 6 h after irradiation, repair of potentially lethal damage (PLD) was observed, resulting in an increase in D/sub q/, while D/sub 0/ remained constant. Treatment of the cells after irradiation with either caffeine or ..beta..-arabinofuranosyladenine (..beta..-araA) or hypertonic medium resulted in an expression of PLD and reduced the D/sub q/ of the survival curve. We measured the rate of the loss of sensitivity of these treatments that we assume reflects the rate of repair of PLD. Results indicate that the shoulder width D/sub q/ of the survival curve in cells irradiated at various stages of the cell cycle results from repair of PLD. It is suggested that the variations observed in cell survival through the cell cycle might reflect variations in the final amount of PLD either repaired or expressed as the cells progress through stages of the cell cycle.

  11. A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

    SciTech Connect

    Granton, Patrick V.; Dubois, Ludwig; Elmpt, Wouter van; Hoof, Stefan J. van; Lieuwes, Natasja G.; De Ruysscher, Dirk

    2014-11-01

    Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated.

  12. The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

    SciTech Connect

    Gillies, N.E.; Obioha, F.I.

    1982-03-01

    When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality.

  13. Respiratory failure and lethal hypotension due to blue-ringed octopus and tetrodotoxin envenomation observed and counteracted in animal models.

    PubMed

    Flachsenberger, W A

    The effects of crude blue-ringed octopus venom gland extract and tetrodotoxin (TTX) on anaesthetised rats and rabbits were studied. Paralysis of the respiratory musculature causing anoxia and cyanosis was overcome with positive, artificial respiration. The second lethal mechanism of the toxins: rapid and severe hypotension, had to be counteracted peripherally, since neural transmission had been drastically reduced by the toxins. Noradrenaline, d-amphetamine, phenylephrine and methoxamine, agonists acting on vascular adrenergic a-receptors, were tested. PMID:3573123

  14. Expression profiling of cancer-related genes in human keratinocytes following non-lethal ultraviolet B irradiation.

    PubMed

    Murakami, T; Fujimoto, M; Ohtsuki, M; Nakagawa, H

    2001-10-01

    Ultraviolet B irradiation initiates and promotes skin cancers, photo-aging, and immune suppression. In order to elucidate the effect of these processes at the level of gene expression, we used cDNA microarray technology to examine the effect of ultraviolet B irradiation on 588 cancer-related genes in human keratinocytes at 1, 6, and 24 h post-irradiation with a mildly cytotoxic dose of ultraviolet B (170 mJ/cm(2)). The viability of the irradiated keratinocytes was 75% at 24 h post-irradiation. Various cytokeratins and transcription factors were up-regulated within 1 h post-irradiation. After 6 h, expression of a variety of genes related to growth regulation (e.g. p21(WAF1), notch 4, and smoothened), apoptosis (e.g. caspase 10, hTRIP, and CRAF1), DNA repair (ERCC1, XRCC1), cytokines (e.g. IL-6, IL-13, TGF-beta, and endothelin 2), and cell adhesion (e.g. RhoE, and RhoGDI) were altered in human keratinocytes. These data suggest the changes in a cascade of gene expression in human keratinocytes occurring within 24 h after UVB exposure. Although the roles of these cellular genes after UVB-irradiation remain to be elucidated, microarray analysis may provide a new view of gene expression in epidermal keratinocytes following UVB exposure.

  15. Inactivation by gamma irradiation of animal viruses in simulated laboratory effluent

    SciTech Connect

    Thomas, F.C.; Ouwerkerk, T.; McKercher, P.

    1982-05-01

    Several animal viruses were treated with gamma radiation from a /sup 60/Co source under conditions which might be found in effluent from an animal disease laboratory. Swine vesicular disease virus, vesicular stomatitis virus, and blue-tongue virus were irradiated in tissues from experimentally infected animals. Pseudorabies virus, fowl plague virus, swine vesicular disease virus, and vesicular stomatitis virus were irradiated in liquid animal feces. All were tested in animals and in vitro. The D/sub 10/ values, that is, the doses required to reduce infectivity by 1 log/sub 10/, were not apparently different from those expected from predictions based on other data and theoretical considerations. The existence of the viruses in pieces of tissues or in liquid feces made no differences in the efficacy of the gamma radiation for inactivating them. Under the ''worst case'' conditions (most protective for virus) simulated in this study, no infectious agents would survive 4.0 Mrads.

  16. Pencil beam scanning dosimetry for large animal irradiation.

    PubMed

    Lin, Liyong; Solberg, Timothy D; Carabe, Alexandro; Mcdonough, James E; Diffenderfer, Eric; Sanzari, Jenine K; Kennedy, Ann R; Cengel, Keith

    2014-09-01

    The space radiation environment imposes increased dangers of exposure to ionizing radiation, particularly during a solar particle event. These events consist primarily of low-energy protons that produce a highly inhomogeneous depth-dose distribution. Here we describe a novel technique that uses pencil beam scanning at extended source-to-surface distances and range shifter (RS) to provide robust but easily modifiable delivery of simulated solar particle event radiation to large animals. Thorough characterization of spot profiles as a function of energy, distance and RS position is critical to accurate treatment planning. At 105 MeV, the spot sigma is 234 mm at 4800 mm from the isocentre when the RS is installed at the nozzle. With the energy increased to 220 MeV, the spot sigma is 66 mm. At a distance of 1200 mm from the isocentre, the Gaussian sigma is 68 mm and 23 mm at 105 MeV and 220 MeV, respectively, when the RS is located on the nozzle. At lower energies, the spot sigma exhibits large differences as a function of distance and RS position. Scan areas of 1400 mm (superior-inferior) by 940 mm (anterior-posterior) and 580 mm by 320 mm are achieved at the extended distances of 4800 mm and 1200 mm, respectively, with dose inhomogeneity <2%. To treat large animals with a more sophisticated dose distribution, spot size can be reduced by placing the RS closer than 70 mm to the surface of the animals, producing spot sigmas below 6 mm.

  17. Pencil beam scanning dosimetry for large animal irradiation

    PubMed Central

    Lin, Liyong; Solberg, Timothy D.; Carabe, Alexandro; Mcdonough, James E.; Diffenderfer, Eric; Sanzari, Jenine K.; Kennedy, Ann R.; Cengel, Keith

    2014-01-01

    The space radiation environment imposes increased dangers of exposure to ionizing radiation, particularly during a solar particle event. These events consist primarily of low-energy protons that produce a highly inhomogeneous depth–dose distribution. Here we describe a novel technique that uses pencil beam scanning at extended source-to-surface distances and range shifter (RS) to provide robust but easily modifiable delivery of simulated solar particle event radiation to large animals. Thorough characterization of spot profiles as a function of energy, distance and RS position is critical to accurate treatment planning. At 105 MeV, the spot sigma is 234 mm at 4800 mm from the isocentre when the RS is installed at the nozzle. With the energy increased to 220 MeV, the spot sigma is 66 mm. At a distance of 1200 mm from the isocentre, the Gaussian sigma is 68 mm and 23 mm at 105 MeV and 220 MeV, respectively, when the RS is located on the nozzle. At lower energies, the spot sigma exhibits large differences as a function of distance and RS position. Scan areas of 1400 mm (superior–inferior) by 940 mm (anterior–posterior) and 580 mm by 320 mm are achieved at the extended distances of 4800 mm and 1200 mm, respectively, with dose inhomogeneity <2%. To treat large animals with a more sophisticated dose distribution, spot size can be reduced by placing the RS closer than 70 mm to the surface of the animals, producing spot sigmas below 6 mm. PMID:24855043

  18. Pencil beam scanning dosimetry for large animal irradiation.

    PubMed

    Lin, Liyong; Solberg, Timothy D; Carabe, Alexandro; Mcdonough, James E; Diffenderfer, Eric; Sanzari, Jenine K; Kennedy, Ann R; Cengel, Keith

    2014-09-01

    The space radiation environment imposes increased dangers of exposure to ionizing radiation, particularly during a solar particle event. These events consist primarily of low-energy protons that produce a highly inhomogeneous depth-dose distribution. Here we describe a novel technique that uses pencil beam scanning at extended source-to-surface distances and range shifter (RS) to provide robust but easily modifiable delivery of simulated solar particle event radiation to large animals. Thorough characterization of spot profiles as a function of energy, distance and RS position is critical to accurate treatment planning. At 105 MeV, the spot sigma is 234 mm at 4800 mm from the isocentre when the RS is installed at the nozzle. With the energy increased to 220 MeV, the spot sigma is 66 mm. At a distance of 1200 mm from the isocentre, the Gaussian sigma is 68 mm and 23 mm at 105 MeV and 220 MeV, respectively, when the RS is located on the nozzle. At lower energies, the spot sigma exhibits large differences as a function of distance and RS position. Scan areas of 1400 mm (superior-inferior) by 940 mm (anterior-posterior) and 580 mm by 320 mm are achieved at the extended distances of 4800 mm and 1200 mm, respectively, with dose inhomogeneity <2%. To treat large animals with a more sophisticated dose distribution, spot size can be reduced by placing the RS closer than 70 mm to the surface of the animals, producing spot sigmas below 6 mm. PMID:24855043

  19. Effect of intrasplenic injection of allogeneic bone marrow cells on the survival of lethally X-irradiated mice

    SciTech Connect

    Imamura, M.; Miyazaki, T.; Okabe, M.; Sakurada, K.; Musashi, M.; Kawamura, K.; Hatakeyama, M.

    1983-01-01

    Radiation chimeras in mice were induced by intrasplenic injection of allogeneic bone marrow cells instead of intravenous injection. Interestingly, the survival time in X-irradiated BALB/c mice inoculated intrasplenically (i.s.) with bone marrow cells from C3H/He mice was markedly prolonged as compared with that in X-irradiated BALB/c mice inoculated i.v. with bone marrow cells from C3H/He mice. However, when C57BL/6 mice were used as donors, a significant difference between i.s. injection and i.v. injection has not been found in survival time at 60 days after X irradiation. On the contrary, when bone marrow cells from BALB/c or C57BL/6 mice were injected into X-irradiated C3H/He mice, i.s. injection gave longer survival days to recipients than did i.v. injection. Based on testing their chimerism, it was suggested that lymphoid cells of donor origin were predominantly identified in almost all BALB/c or C3H/He recipients which were inoculated i.s. with bone marrow cells from C57BL/6 mice. However, somewhat incomplete chimerism was observed when the C3H/He to BALB/c donor-recipient combination was used and vice versa.

  20. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    PubMed

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  1. Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body. gamma. irradiation

    SciTech Connect

    Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

    1981-11-01

    The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body ..gamma.. irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice.

  2. Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

    SciTech Connect

    Beetham, K.L.; Tolmach, L.J.

    1984-12-01

    HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage.

  3. Biological effectiveness of neutron irradiation on animals and man

    SciTech Connect

    Straume, T.

    1982-11-01

    Neutron experiments on a highly radiosensitive in vivo system - oocytes in mice - provide new insight into the nature of the radiosensitive targets of these important cells. With the radiobiological literature as background, neutron data from animals and humans are integrated, and the controversial question of radiation protection standards for neutrons is addressed. Oocyte killing in juvenile mice by 0.43-MeV, /sup 252/Cf-fission, and 15 MeV neutrons, compared with that by /sup 60/Co gamma rays, yields unusually low neutron RBEs (relative biological effectiveness). At 0.1 rad of 0.43-MeV neutrons the RBE is only 1.8, contrasting greatly with values of 100 or more reported at low-doses for other endpoints. In mice just prior to birth, however, when oocytes are less radiosensitive, the neutron RBE is much higher, similar to values for most other mammalian endpoints. This dramatic change in neutron RBE with mouse age (occurring within 2 to 3 days) can be explained as the result of a shift from a less radiosensitive target (presumably nuclear DNA) to a much more radiosensitive one (probably the oocyte plasma membrane). Using various approaches, a value for the neutron Quality Factor (Q, a radiation protection standard) is estimated as 17 (+-100%), much lower than 100 which has been suggested. With the large uncertainty, 17 is not markedly different from the value of 10 presently in general use.

  4. An animal model of prophylactic cranial irradiation: Histologic effects at acute, early and delayed stages

    SciTech Connect

    Mildenberger, M.; Beach, T.G.; McGeer, E.G.; Ludgate, C.M. )

    1990-05-01

    Wistar rats (body wt. 200 g) were subjected to a fractionated course of radiation similar to that used in prophylactic brain irradiation for small cell carcinoma of the lung (2000 cGy in 5 fractions over 5 days with {sup 60}Co). Effects of this regimen were assessed by histologic examination of brain sections at 1 week, 1 month and 6 months post-irradiation. With conventional stains there were no apparent differences between control and irradiated brains at any of the post-irradiation intervals. Immunohistochemistry for neurotransmitter synthetic enzymes tyrosine hydroxylase and glutamate decarboxylase, as well as histochemistry for acetylcholinesterase, failed to uncover any changes in the irradiated animals. Immunohistochemistry for glial fibrillary acidic protein, an astrocyte marker, also showed no differences in the irradiated groups. However, an antibody against a major histocompatibility complex, class II antigen (OX-6) revealed a microglial response in grey and white matter beginning at 1 month and increasing up to the 6 month post-irradiation interval. The neuroanatomical basis for this microglial response was suggested by the results of silver stains for nerve axons, which revealed axonal loss in striatal white matter bundles in a pattern implicating vascular insufficiency.

  5. Effects of low power laser irradiation on bone healing in animals: a meta-analysis

    PubMed Central

    2010-01-01

    Purpose The meta-analysis was performed to identify animal research defining the effects of low power laser irradiation on biomechanical indicators of bone regeneration and the impact of dosage. Methods We searched five electronic databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised Clinical Trials) for studies in the area of laser and bone healing published from 1966 to October 2008. Included studies had to investigate fracture healing in any animal model, using any type of low power laser irradiation, and use at least one quantitative biomechanical measures of bone strength. There were 880 abstracts related to the laser irradiation and bone issues (healing, surgery and assessment). Five studies met our inclusion criteria and were critically appraised by two raters independently using a structured tool designed for rating the quality of animal research studies. After full text review, two articles were deemed ineligible for meta-analysis because of the type of injury method and biomechanical variables used, leaving three studies for meta-analysis. Maximum bone tolerance force before the point of fracture during the biomechanical test, 4 weeks after bone deficiency was our main biomechanical bone properties for the Meta analysis. Results Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08 - 1.37, p 0.028). While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue during the healing process in animal models. PMID:20047683

  6. A small animal image guided irradiation system study using 3D dosimeters

    NASA Astrophysics Data System (ADS)

    Qian, Xin; Admovics, John; Wuu, Cheng-Shie

    2015-01-01

    In a high resolution image-guided small animal irradiation platform, a cone beam computed tomography (CBCT) is integrated with an irradiation unit for precise targeting. Precise quality assurance is essential for both imaging and irradiation components. The conventional commissioning techniques with films face major challenges due to alignment uncertainty and labour intensive film preparation and scanning. In addition, due to the novel design of this platform the mouse stage rotation for CBCT imaging is perpendicular to the gantry rotation for irradiation. Because these two rotations are associated with different mechanical systems, discrepancy between rotation isocenters exists. In order to deliver x-ray precisely, it is essential to verify coincidence of the imaging and the irradiation isocenters. A 3D PRESAGE dosimeter can provide an excellent tool for checking dosimetry and verifying coincidence of irradiation and imaging coordinates in one system. Dosimetric measurements were performed to obtain beam profiles and percent depth dose (PDD). Isocentricity and coincidence of the mouse stage and gantry rotations were evaluated with starshots acquired using PRESAGE dosimeters. A single PRESAGE dosimeter can provide 3 -D information in both geometric and dosimetric uncertainty, which is crucial for translational studies.

  7. Precise image-guided irradiation of small animals: a flexible non-profit platform.

    PubMed

    Tillner, Falk; Thute, Prasad; Löck, Steffen; Dietrich, Antje; Fursov, Andriy; Haase, Robert; Lukas, Mathias; Rimarzig, Bernd; Sobiella, Manfred; Krause, Mechthild; Baumann, Michael; Bütof, Rebecca; Enghardt, Wolfgang

    2016-04-21

    Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks.

  8. Precise image-guided irradiation of small animals: a flexible non-profit platform

    NASA Astrophysics Data System (ADS)

    Tillner, Falk; Thute, Prasad; Löck, Steffen; Dietrich, Antje; Fursov, Andriy; Haase, Robert; Lukas, Mathias; Rimarzig, Bernd; Sobiella, Manfred; Krause, Mechthild; Baumann, Michael; Bütof, Rebecca; Enghardt, Wolfgang

    2016-04-01

    Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks.

  9. Natural resistance of lethally irradiated F1 hybrid mice to parental marrow grafts is a function of H-2/Hh-restricted effectors

    SciTech Connect

    Daley, J.P.; Nakamura, I.

    1984-04-01

    The natural resistance of F1 hybrid mice against parental bone marrow grafts is thought to be mediated by natural killer (NK)-like effector cells. However, unlike the NK cell activity against a wide range of tumors and normal cells, hybrid resistance is characterized by the immunogenetic specificity controlled by a set of unique noncodominant genes denoted as Hh. Two alternative hypotheses can account for the specificity. Thus, the specificity may reflect either the Hh restriction of effectors or the Hh gene control of mechanisms regulating non-Hh-restricted effector activity. In this study, therefore, we tested the recognition specificity of putative effectors mediating hybrid resistance in lethally irradiated H-2b/d and H-2b/k F1 hybrid mice to the engraftment of parental H-2b bone marrow. As a direct means of defining the effector specificity, rejection of parental bone marrow grafts was subjected to competitive inhibition in situ by irradiated tumor cells. Of the 16 independent lines of lymphoma and other hemopoietic tumor cells tested, the ability to inhibit hybrid resistance was the exclusive property of all tumors derived from mice homozygous for the H-2Db region, regardless of whether the tumor cells were susceptible or resistant to NK cell-mediated cytotoxicity in vitro. Four cell lines heterozygous for the H-2Db were noninhibitory, including one that is susceptible to natural killing. Pretreatment of the F1 hosts with an interferon inducer augmented the resistance with no alteration in the recognition specificity of effector cells. Therefore, natural resistance to parental H-2b bone marrow grafts was mediated by effectors restricted by the H-2Db/Hh-1b gene(s), and not by the nonrestricted NK cells detectable in conventional in vitro assays.

  10. Action of caffeine on x-irradiated HeLa cells. V. Identity of the sector of cells that expresses potentially lethal damage in G/sub 1/ and G/sub 2/

    SciTech Connect

    Beetham, K.L.; Tolmach, L.J.

    1982-07-01

    When HeLa S3 cells are irradiated in early G/sub 1/ with 4 Gy of 220-kV x rays and are then incubated in growth medium containing up to 5 mM caffeine, survival is reduced (as reported previously), reaching a concentration-dependent plateau. Cell killing presumably occurs as a result of the fixation of a portion of the potentially lethal damage the cells contain. These cells respond to continued treatment with caffeine at concentrations greater than 2 mM during S, but less so than during G/sub 1/. When they reach G/sub 2/ arrest, however, extensive cell killing again occurs (reported previously), presumably also the result of potentially lethal damage fixation. G/sub 1/-irradiated cultures that are treated with caffeine either continuously at a concentration in the range 1 to 5 mM, or at 10 mM for 8 hr and subsequently with the low concentration, achieve the same survival level in G/sub 2/, provided that the potentially lethal damage is not repaired during G/sub 1/ and S. Repair seems to be completely inhibited in the presence of 3 to 4 mM caffeine. The results indicate that fixation of potentially lethal damage occurs in the same sector of cells in G/sub 1/ and G/sub 2/, suggesting that the same cellular lesion gives rise to cell killing in the two phases.

  11. Evaluation of a cone beam computed tomography geometry for image guided small animal irradiation.

    PubMed

    Yang, Yidong; Armour, Michael; Wang, Ken Kang-Hsin; Gandhi, Nishant; Iordachita, Iulian; Siewerdsen, Jeffrey; Wong, John

    2015-07-01

    The conventional imaging geometry for small animal cone beam computed tomography (CBCT) is that a detector panel rotates around the head-to-tail axis of an imaged animal ('tubular' geometry). Another unusual but possible imaging geometry is that the detector panel rotates around the anterior-to-posterior axis of the animal ('pancake' geometry). The small animal radiation research platform developed at Johns Hopkins University employs the pancake geometry where a prone-positioned animal is rotated horizontally between an x-ray source and detector panel. This study is to assess the CBCT image quality in the pancake geometry and investigate potential methods for improvement. We compared CBCT images acquired in the pancake geometry with those acquired in the tubular geometry when the phantom/animal was placed upright simulating the conventional CBCT geometry. Results showed signal-to-noise and contrast-to-noise ratios in the pancake geometry were reduced in comparison to the tubular geometry at the same dose level. But the overall spatial resolution within the transverse plane of the imaged cylinder/animal was better in the pancake geometry. A modest exposure increase to two folds in the pancake geometry can improve image quality to a level close to the tubular geometry. Image quality can also be improved by inclining the animal, which reduces streak artifacts caused by bony structures. The major factor resulting in the inferior image quality in the pancake geometry is the elevated beam attenuation along the long axis of the phantom/animal and consequently increased scatter-to-primary ratio in that orientation. Not withstanding, the image quality in the pancake-geometry CBCT is adequate to support image guided animal positioning, while providing unique advantages of non-coplanar and multiple mice irradiation. This study also provides useful knowledge about the image quality in the two very different imaging geometries, i.e. pancake and tubular geometry, respectively.

  12. Evaluation of a cone beam computed tomography geometry for image guided small animal irradiation

    NASA Astrophysics Data System (ADS)

    Yang, Yidong; Armour, Michael; Kang-Hsin Wang, Ken; Gandhi, Nishant; Iordachita, Iulian; Siewerdsen, Jeffrey; Wong, John

    2015-07-01

    The conventional imaging geometry for small animal cone beam computed tomography (CBCT) is that a detector panel rotates around the head-to-tail axis of an imaged animal (‘tubular’ geometry). Another unusual but possible imaging geometry is that the detector panel rotates around the anterior-to-posterior axis of the animal (‘pancake’ geometry). The small animal radiation research platform developed at Johns Hopkins University employs the pancake geometry where a prone-positioned animal is rotated horizontally between an x-ray source and detector panel. This study is to assess the CBCT image quality in the pancake geometry and investigate potential methods for improvement. We compared CBCT images acquired in the pancake geometry with those acquired in the tubular geometry when the phantom/animal was placed upright simulating the conventional CBCT geometry. Results showed signal-to-noise and contrast-to-noise ratios in the pancake geometry were reduced in comparison to the tubular geometry at the same dose level. But the overall spatial resolution within the transverse plane of the imaged cylinder/animal was better in the pancake geometry. A modest exposure increase to two folds in the pancake geometry can improve image quality to a level close to the tubular geometry. Image quality can also be improved by inclining the animal, which reduces streak artifacts caused by bony structures. The major factor resulting in the inferior image quality in the pancake geometry is the elevated beam attenuation along the long axis of the phantom/animal and consequently increased scatter-to-primary ratio in that orientation. Not withstanding, the image quality in the pancake-geometry CBCT is adequate to support image guided animal positioning, while providing unique advantages of non-coplanar and multiple mice irradiation. This study also provides useful knowledge about the image quality in the two very different imaging geometries, i.e. pancake and tubular geometry

  13. SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

    SciTech Connect

    Grams, M; Wilson, Z; Sio, T; Beltran, C; Tryggestad, E; Gupta, S; Blackwell, C; McCollough, K; Sarkaria, J; Furutani, K

    2014-06-01

    Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons from a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra.

  14. DNA polymerase I is crucial for the repair of potentially lethal damage caused by the indirect effects of X irradiation in Escherichia coli

    SciTech Connect

    Billen, D.

    1985-07-01

    The radiosensitivity of an Escherichia coli mutant deficient in DNA polymerase I was measured in the presence of OH radical scavengers. The extreme X-ray sensitivity of the mutant could be abolished by OH radical scavengers if a sufficiently high level of radioprotector was present. There was a direct correlation between the OH radical scavenging activity of the chemicals tested (NO/sub 2//sup -/, n-butanol, glycerol, t-amyl alcohol, and t-butanol) and their protective ability. The author interprets the data as showing that the indirect actions of X rays (primarily OH radicals) result in major damage to the bacterial DNA which in large part consists of potentially lethal lesions. This potentially lethal damage is repaired through an enzymatic pathway requiring DNA polymerase I. I. In the mutant lacking DNA polymerase I, these potentially lethal lesions are expressed as cell lethality.

  15. Are three forms of potentially lethal damage expressed after X irradiation by treatment with hypertonic solutions in Chinese hamster V79 cells?

    SciTech Connect

    Ikebuchi, Makoto; Kimura, Hiroshi; Aoyama, Takashi; Hill, C.K.

    1995-01-01

    X rays have been shown to induce two forms of potentially lethal damage (PLD), {open_quotes}fast-repairing{close_quotes} PLD and {open_quotes}slowly repairing PLD, whose repair is completed in 1 h and 4-6 h, respectively. In this study three modes of treatment with hypertonic solutions containing different NaCl concentrations for different durations (0.5 M for 30 min, 0.225 M for 4 h, 0.16 M for 16 h) were examined to determine which form of PLD is expressed under each condition. These three modes of treatment enhanced the cell-killing action of X rays on actively growing V79 cells due to fixation of PLD. The kinetics of recovery from PLD was assessed by delayed treatments with hypertonic solutions. Cells exposed to one of the three treatments had completed recovery times of 1, 4 and 8 h, respectively, suggesting the possibility that these three modes of treatment cause the expression of different forms of PLD. As has been reported, treatment with 0.5 M NaCl for 30 min expressed fast-repairing PLD. The independence of the PLD expressed after 0.5 M NaCl for 30 min was shown by combined treatment with the two modes, which reduced survival to the level that would be reached if the two modes acted independently. The data on the recovery time and on the inhibition by 0.225 M NaCl of recovery from slowly repairing PLD in plateau-phase cells indicated that the PLD expressed after 0.225 M NaCl for 4 h may be related to slowly repairing PLD. The combined treatment of 0.16 M NaCl for 16 h with 0.225 M NaCl for 4 h indicated independent action, albeit incomplete, of the PLD expressed after 0.16 M NaCl for 16 h from slowly repairing PLD. We propose for the first time that {open_quotes}very slowly repairing{close_quotes} PLD is expressed after 0.16 M NaCl for 16 h in exponentially growing cells and that therefore three forms of PLD are expressed by hypertonic treatments after X irradiation. 31 refs., 9 figs.

  16. Feasibility of small animal cranial irradiation with the microRT system

    SciTech Connect

    Kiehl, Erich L.; Stojadinovic, Strahinja; Malinowski, Kathleen T.; Limbrick, David; Jost, Sarah C.; Garbow, Joel R.; Rubin, Joshua B.; Deasy, Joseph O.; Khullar, Divya; Izaguirre, Enrique W.; Parikh, Parag J.; Low, Daniel A.; Hope, Andrew J.

    2008-10-15

    Purpose: To develop and validate methods for small-animal CNS radiotherapy using the microRT system. Materials and Methods: A custom head immobilizer was designed and built to integrate with a pre-existing microRT animal couch. The Delrin couch-immobilizer assembly, compatible with multiple imaging modalities (CT, microCT, microMR, microPET, microSPECT, optical), was first imaged via CT in order to verify the safety and reproducibility of the immobilization method. Once verified, the subject animals were CT-scanned while positioned within the couch-immobilizer assembly for treatment planning purposes. The resultant images were then imported into CERR, an in-house-developed research treatment planning system, and registered to the microRTP treatment planning space using rigid registration. The targeted brain was then contoured and conformal radiotherapy plans were constructed for two separate studies: (1) a whole-brain irradiation comprised of two lateral beams at the 90 degree sign and 270 degree sign microRT treatment positions and (2) a hemispheric (left-brain) irradiation comprised of a single A-P vertex beam at the 0 degree sign microRT treatment position. During treatment, subject animals (n=48) were positioned to the CERR-generated treatment coordinates using the three-axis microRT motor positioning system and were irradiated using a clinical Ir-192 high-dose-rate remote after-loading system. The radiation treatment course consisted of 5 Gy fractions, 3 days per week. 90% of the subjects received a total dose of 30 Gy and 10% received a dose of 60 Gy. Results: Image analysis verified the safety and reproducibility of the immobilizer. CT scans generated from repeated reloading and repositioning of the same subject animal in the couch-immobilizer assembly were fused to a baseline CT. The resultant analysis revealed a 0.09 mm average, center-of-mass translocation and negligible volumetric error in the contoured, murine brain. The experimental use of the head

  17. Dosimetric characterization of an image-guided stereotactic small animal irradiator

    NASA Astrophysics Data System (ADS)

    Pidikiti, R.; Stojadinovic, S.; Speiser, M.; Song, K. H.; Hager, F.; Saha, D.; Solberg, T. D.

    2011-04-01

    Small animal irradiation provides an important tool used by preclinical studies to assess and optimize new treatment strategies such as stereotactic ablative radiotherapy. Characterization of radiation beams that are clinically and geometrically scaled for the small animal model is uniquely challenging for orthovoltage energies and minute field sizes. The irradiator employs a commercial x-ray device (XRAD 320, Precision x-ray, Inc.) with a custom collimation system to produce 1-10 mm diameter beams and a 50 mm reference beam. Absolute calibrations were performed using the AAPM TG-61 methodology. Beam's half-value layer (HVL) and timer error were measured with an ionization chamber. Percent depth dose (PDD), output factors (OFs) and off-axis ratios were measured using radiochromic film, a diode and a pinpoint ionization chamber at 19.76 and 24.76 cm source-to-surface distance (SSD). PDD measurements were also compared with Monte Carlo (MC) simulations. In-air and in-water absolute calibrations for the reference 50 mm diameter collimator at 19.76 cm SSD were measured as 20.96 and 20.79 Gy min-1, respectively, agreeing within 0.8%. The HVL at 250 kVp and 15 mAs was measured to be 0.45 mm Cu. The reference field PDD MC simulation results agree with measured data within 3.5%. PDD data demonstrate typical increased penetration with increasing field size and SSD. For collimators larger than 5 mm in diameter, OFs measured using film, an ion chamber and a diode were within 3% agreement.

  18. 78 FR 34565 - Irradiation in the Production, Processing, and Handling of Animal Feed and Pet Food; Electron...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-10

    ..., and Handling of Animal Feed and Pet Food; Electron Beam and X-Ray Sources for Irradiation of Poultry... generated from machine sources at energy levels not to exceed 10 million electron volts (MeV); (3) X-rays... this chapter; or (4) X-rays generated from machine sources using tantalum or gold as the...

  19. Immune reactivity after high-dose irradiation

    SciTech Connect

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-03-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

  20. Effect of active species on animal cells in culture media induced by DBD Plasma irradiation using air

    NASA Astrophysics Data System (ADS)

    Ohtsubo, Tetsuya; Ono, Reoto; Hayashi, Nobuya

    2015-09-01

    Little has been reported on action mechanism of active species produced by plasmas affecting living cells. In this study, active species in culture medium generated by torch type DBD and variations of animal cells are attempted to be clarified. Animal cells are irradiated by DBD plasma through various media such as DMEM, PBS and distilled water. Irradiation period is 1 to 15 min. The distance between the lower tip of plasma touch and the surface of the medium is 10 mm. Concentrations of NO2 -, O2 in liquid are measured. After the irradiation, the cells were cultivated in culture medium and their modifications are observed by microscope and some chemical reagents. Concentration of NO2 - and H2 O2 in all media increased with discharge period. Increase rate of NO2 -concentration is much higher than that of hydrogen peroxide. After plasma irradiation for 15 min, concentrations of NO2 were 80 mg/L in DMEM, 30 mg/L in PBS and 15 mg/L in distilled water. Also, the concentration of H2 O2 became 3mg/L in DMEM, 6.5 mg/L in PBS and 6.5mg/L in distilled water. The significant inactivation of cells was observed in the PBS. Above results indicate that, in this experiment, H2 O2 or OH radicals would affect animal cells in culture media.

  1. Transcriptome Analysis of Porphyrin-Accumulated and X-Ray-Irradiated Cell Cultures under Limited Proliferation and Non-Lethal Conditions

    PubMed Central

    Takahashi, Junko; Misawa, Masaki; Iwahashi, Hitoshi

    2015-01-01

    5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer used in photodynamic therapy. It accumulates in tumor cells and subsequently metabolizes to protoporphyrin IX (PpIX), which generates singlet oxygen after light irradiation. PpIX enhances the generation of reactive oxygen species following physicochemical interactions with X-rays. ALA-based treatment using fractionated doses of irradiation suppressed tumor growth in a mouse melanoma model. To study the transcriptomic effects of PpIX, microarray analyses were conducted using HeLa cells with limited proliferation capacity. Based on the p-values (p < 0.01), we selected genes showing altered expression in each treatment group with reference to the non-treatment (NT) group. We detected 290, 196 and 28 upregulated genes, as well as 203, 146 and 36 downregulated genes after a 6 h-long PpIX treatment (1 μg/mL) prior to 3 Gy X-ray irradiation (PpIX-XT), 3 Gy X-ray irradiation alone (XT) and PpIX treatment alone (PpIXT), respectively. Functional analysis revealed that a majority of the regulated genes in the XT and PpIX-XT groups were related to cell-cycle arrest. The XT and PpIX-XT groups differed in the quantity, but not in the quality of their gene expression. The combined effect of PpIX and X-ray irradiation sensitized HeLa cells to X-ray treatment.

  2. Evaluation of the radioprotective effect of the leaf extract of Syzygium cumini (Jamun) in mice exposed to a lethal dose of gamma-irradiation.

    PubMed

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2003-06-01

    The effects of various concentrations (5, 10, 20, 30, 40, 50, 60, and 80 mg/kg body weight (b.wt.) of the leaf extracts of Syzygium cumini Linn. and Eugenia cumini (SCE, black plum, Jamun, family Myrtaceae) on the radiation-induced sickness and mortality in mice exposed to 10 Gy gamma-irradiation were studied. The treatment of mice with different doses of SCE, consecutively for five days before irradation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the nondrug-treated irradiated controls. All doses of SCE provied protection against the gastrointestinal death increasing the survival by 66.66% after treatment with 20, 30, and 40 mg/kg SCE versus a 12% survival in the irradiated control group (oil + irradiation). Similarly, SCE provided protection against the radiation-induced bone marrow death in mice treated with 10-60 mg/kg b.wt. of SCE. However, the best protection was obtained for 30 mg/kg b.wt. SCE, where the number of, survivors after 30 days post-irradiation was highest (41.66%) when compared with the other doses of SCE. PMID:12866620

  3. Nd:YAG laser irradiation in conjunction with cryogen spray cooling induces deep and spatially selective photocoagulation in animal models.

    PubMed

    Anvari, B; Tanenbaum, B S; Hoffman, W; Said, S; Milner, T E; Liaw, L H; Nelson, J S

    1997-02-01

    Successful laser treatment of haemangiomas requires selective photocoagulation of subsurface targeted blood vessels without thermal damage to the overlying epidermis. We present an in vivo experimental procedure, using a chicken comb animal model, and an infrared feedback system to deliver repetitive cryogen spurts (of the order of milliseconds) during continuous Nd:YAG laser irradiation. Gross and histologic observations show deep-tissue photocoagulation is achieved, while superficial structures are protected from thermal injury due to cryogen spray cooling. Experimental observation of epidermis protection in chicken comb animal models suggests selective photocoagulation of subsurface targeted blood vessels for successful treatment of haemangiomas can be achieved by repetitive applications of a cryogen spurt during continuous Nd:YAG laser irradiation.

  4. In vitro quantitation of lethal and physiologic effects of total body irradiation on stromal and hematopoietic stem cells in continuous bone marrow cultures from Rf mice

    SciTech Connect

    Greenberger, J.S.; Eckner, R.J.; Otten, J.A.; Tennant, R.W.

    1982-07-01

    The effects of in vivo total body irradiation (TBI) and interval from TBI to explant of marrow on: stromal cell proliferation in vitro; stromal cell support of hematopoiesis in continuous bone marrow culture; and generation of WEHI-3 growth factor (GF)-dependent lines of hematopoietic progenitor cells were evaluated. Explant of marrow at 2, 4, 5, or 6 months after single fraction TBI (300-800 rad) was associated with decreased longevity of hemopoiesis and a decrease in the proliferative capacity of fibroblastic adherent-stromal colony forming cells (CFUf) as measured by colony size at 14 days and number of colonies per 10/sup 6/ cells plated. In contrast, explant of marrow 8 to 24 months after TBI produced cultures with longevity that was indistinguishable from age-matched control cultures (19-24 weeks). Marrow from irradiated first and second generation recipients of serially transferred marrow demonstrated a similar 7-month in vivo recovery period; however, the plateau maximum duration of hemopoiesis did not return to control levels. Purified stromal cell cultures were prepared by corticosteroid-deprivation of explanted marrow for 28 days and were then engrafted in vitro with marrow from C57BL/6J or RfM/UN mice that had been irradiated 1 month previously. Hemopoiesis in these cultures was restored, and they produced GM-CFUc and granulocytes for 15-24 weeks. Thus, healthy stroma supported growth of recently irradiated hemopoietic cells in vitro. Indirect effects of x-irradiation on hemopoietic stem cells through damage and repair in the stromal cell compartment can be effectively studied with the present bone marrow culture system. (JMT)

  5. The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

    SciTech Connect

    Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

    2013-08-01

    Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

  6. Multi-institutional dosimetric and geometric commissioning of image-guided small animal irradiators

    SciTech Connect

    Lindsay, P. E.; Granton, P. V.; Hoof, S. van; Hermans, J.; Gasparini, A.; Jelveh, S.; Clarkson, R.; Kaas, J.; Wittkamper, F.; Sonke, J.-J.; Verhaegen, F.; Jaffray, D. A.

    2014-03-15

    Purpose: To compare the dosimetric and geometric properties of a commercial x-ray based image-guided small animal irradiation system, installed at three institutions and to establish a complete and broadly accessible commissioning procedure. Methods: The system consists of a 225 kVp x-ray tube with fixed field size collimators ranging from 1 to 44 mm equivalent diameter. The x-ray tube is mounted opposite a flat-panel imaging detector, on a C-arm gantry with 360° coplanar rotation. Each institution performed a full commissioning of their system, including half-value layer, absolute dosimetry, relative dosimetry (profiles, percent depth dose, and relative output factors), and characterization of the system geometry and mechanical flex of the x-ray tube and detector. Dosimetric measurements were made using Farmer-type ionization chambers, small volume air and liquid ionization chambers, and radiochromic film. The results between the three institutions were compared. Results: At 225 kVp, with 0.3 mm Cu added filtration, the first half value layer ranged from 0.9 to 1.0 mm Cu. The dose-rate in-air for a 40 × 40 mm{sup 2} field size, at a source-to-axis distance of 30 cm, ranged from 3.5 to 3.9 Gy/min between the three institutions. For field sizes between 2.5 mm diameter and 40 × 40 mm{sup 2}, the differences between percent depth dose curves up to depths of 3.5 cm were between 1% and 4% on average, with the maximum difference being 7%. The profiles agreed very well for fields >5 mm diameter. The relative output factors differed by up to 6% for fields larger than 10 mm diameter, but differed by up to 49% for fields ≤5 mm diameter. The mechanical characteristics of the system (source-to-axis and source-to-detector distances) were consistent between all three institutions. There were substantial differences in the flex of each system. Conclusions: With the exception of the half-value layer, and mechanical properties, there were significant differences between the

  7. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

  8. Laminin 332 Deposition is Diminished in Irradiated Skin in an Animal Model of Combined Radiation and Wound Skin Injury

    PubMed Central

    Jourdan, M. M.; Lopez, A.; Olasz, E. B.; Duncan, N. E.; Demara, M.; Kittipongdaja, W.; Fish, B. L.; Mäder, M.; Schock, A.; Morrow, N. V.; Semenenko, V. A.; Baker, J. E.; Moulder, J. E.; Lazarova, Z.

    2011-01-01

    Skin exposure to ionizing radiation affects the normal wound healing process and greatly impacts the prognosis of affected individuals. We investigated the effect of ionizing radiation on wound healing in a rat model of combined radiation and wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation (10–40 Gy) was delivered to the skin without significant exposure to internal organs. At 1 h postirradiation, two skin wounds were made on the back of each rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days postirradiation. The wound areas were measured, and tissue samples were evaluated for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results clearly demonstrate that radiation exposure significantly delayed wound healing in a dose-related manner. Evaluation of irradiated and wounded skin showed decreased deposition of laminin 332 protein in the epidermal basement membrane together with an elevated expression of all three laminin 332 genes within 3 days postirradiation. The elevated laminin 332 gene expression was paralleled by an elevated gene and protein expression of MMP2, suggesting that the reduced amount of laminin 332 in irradiated skin is due to an imbalance between laminin 332 secretion and its accelerated processing by elevated tissue metalloproteinases. Western blot analysis of cultured rat keratinocytes showed decreased laminin 332 deposition by irradiated cells, and incubation of irradiated keratinocytes with MMP inhibitor significantly increased the amount of deposited laminin 332. Furthermore, irradiated keratinocytes exhibited a longer time to close an artificial wound, and this delay was partially corrected by seeding keratinocytes on laminin 332-coated plates. These data strongly suggest that laminin 332 deposition is inhibited by ionizing radiation and, in combination with slower keratinocyte migration, can contribute to the delayed wound healing of irradiated skin. PMID

  9. Petitioning process for irradiated foods and animal feeds in North America

    NASA Astrophysics Data System (ADS)

    Marcotte, Michelle; Kunstadt, Peter

    1993-07-01

    The lack of sufficient regulatory approvals continues to delay the commercial application of food irradiation in several countries. Often, the regulatory approval process itself appears too challenging and approvals are not even requested. We believe that petitions can be successful and want to encourage interested parties to submit good quality approval petitions to the regulatory authorities. The objective of this paper is to review petition requirements so that researchers and companies in other countries will be able to prepare petitions requesting approval for the import and sale of irradiated foods into North America.

  10. SU-E-T-376: 3-D Commissioning for An Image-Guided Small Animal Micro- Irradiation Platform

    SciTech Connect

    Qian, X; Wuu, C; Admovics, J

    2014-06-01

    Purpose: A 3-D radiochromic plastic dosimeter has been used to cross-test the isocentricity of a high resolution image-guided small animal microirradiation platform. In this platform, the mouse stage rotating for cone beam CT imaging is perpendicular to the gantry rotation for sub-millimeter radiation delivery. A 3-D dosimeter can be used to verify both imaging and irradiation coordinates. Methods: A 3-D dosimeter and optical CT scanner were used in this study. In the platform, both mouse stage and gantry can rotate 360° with rotation axis perpendicular to each other. Isocentricity and coincidence of mouse stage and gantry rotations were evaluated using star patterns. A 3-D dosimeter was placed on mouse stage with center at platform isocenter approximately. For CBCT isocentricity, with gantry moved to 90°, the mouse stage rotated horizontally while the x-ray was delivered to the dosimeter at certain angles. For irradiation isocentricity, the gantry rotated 360° to deliver beams to the dosimeter at certain angles for star patterns. The uncertainties and agreement of both CBCT and irradiation isocenters can be determined from the star patterns. Both procedures were repeated 3 times using 3 dosimeters to determine short-term reproducibility. Finally, dosimeters were scanned using optical CT scanner to obtain the results. Results: The gantry isocentricity is 0.9 ± 0.1 mm and mouse stage rotation isocentricity is about 0.91 ± 0.11 mm. Agreement between the measured isocenters of irradiation and imaging coordinates was determined. The short-term reproducibility test yielded 0.5 ± 0.1 mm between the imaging isocenter and the irradiation isocenter, with a maximum displacement of 0.7 ± 0.1 mm. Conclusion: The 3-D dosimeter can be very useful in precise verification of targeting for a small animal irradiation research. In addition, a single 3-D dosimeter can provide information in both geometric and dosimetric uncertainty, which is crucial for translational studies.

  11. [The specific features of the distribution of 4-metoxyhydroxybenzene in the organism of the warm-blooded animals suffering lethal intoxication].

    PubMed

    Shormanov, V K; Astashkina, A P; Ostanin, M A; Grishechko, O I; Tsatsua, E P

    2016-01-01

    This work was designed to study the distribution of 4-metoxyhydroxybenzene in the organism of the omnivorous warm-blooded animals (rats) after the intragastric administration of this poisonous compound at a dose three-fold greater than the LD50 value. The administered 4-metoxyhydroxybenzene was isolated from the organs and blood of the experimental animals by exposing the biological tissues to acetone with subsequent purification on a silica gel L 40/100 mcm using a hexane:dioxane:propanol-2 (20:5:1) as the mobile phase. The identification and quantitation of 4-metoxyhydroxybenzene were carried out with the use of TLC, GC-MS, and UF-spectrophotometry. It was shown that the administered 4-metoxyhydroxybenzene remained unmetabolized in the internal organs and blood of the poisoned experimental animals. The largest amounts of 4-metoxyhydroxybenzene were found in the stomach contents (2584,92±117,47), brain (59.49±6.05), contents of small intestines (28.21±3.77), and kidneys (26.13±1.64). PMID:27500483

  12. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  13. Studies on radiosensitive lines of Drosophila. IX. Analysis of fertility and frequency of dominant lethal mutations in the gamma-irradiated females of the mutant line rad(2)201/sup G1/

    SciTech Connect

    Varentsova, E.R.; Sharygin, V.I.; Khromykh, Yu.M.

    1986-03-01

    Fertility and frequency of dominant lethal mutations (DLM) induced by gamma rays in females at the age of 0-5 h and 5-7 days were studied in the radiosensitive mutant rad(2)201/sup G1/ of Drosophila. It has been found that the oocytes of mutant lines are more radiosensitive as compared to those of the wild type flies when compared on the basis of DLM frequency obtained through the entire maturation period. The early oocytes of stages 2-7, i.e., at the stages corresponding to the recombination-defective properties of mutation rad(2)201/sup g1/ are the most sensitive. It has also been demonstrated that the gamma-ray doses exceeding 10 Gy cause a strong sterilizing effect in the mutant females as a result of destruction and resorption of the egg chamber, irradiated at the stages of previtellogenic growth of oocytes. In the radiosensitive mutant females, the sensitivity of the oocytes for DLM induction does not correlate with the sensitivity of the ovarian follicles toward the resorbing effect of gamma rays. The possible involvement of the mutant locus in the genetic processes in different specialized cells of the sexual pathway in Drosophila is discussed.

  14. Anthropomorphic Phantoms for Confirmation of Linear Accelerator-Based Small Animal Irradiation.

    PubMed

    Perks, Julian R; Lucero, Steven; Monjazeb, Arta M; Li, Jian Jian

    2015-03-01

    Three dimensional (3D) scanning and printing technology is utilized to create phantom models of mice in order to assess the accuracy of ionizing radiation dosing from a clinical, human-based linear accelerator. Phantoms are designed to simulate a range of research questions, including irradiation of lung tumors and primary subcutaneous or orthotopic tumors for immunotherapy experimentation. The phantoms are used to measure the accuracy of dose delivery and then refine it to within 1% of the prescribed dose.

  15. Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA).

    PubMed

    Noh, Jin-Yong; Park, Jae-Keun; Lee, Dong-Hun; Yuk, Seong-Su; Kwon, Jung-Hoon; Lee, Sang-Won; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2016-01-01

    Highly pathogenic avian influenza (HPAI) and Newcastle disease (ND) are considered as the most devastating poultry infections, owing to their worldwide distribution and economical threat. Vaccines have been widely used to control these diseases in the poultry industry in endemic countries. However, vaccination policy without differentiating infected animals from vaccinated animals (DIVA) makes the virus surveillance difficult. In this study, we developed a bivalent virus-like particle (VLP) vaccine that is composed of the hemagglutinin (HA) and matrix 1 (M1) proteins of the H5N1 HPAI virus (HPAIV) and a chimeric protein containing the ectodomain of the ND virus (NDV) fusion (F) protein fused with the cytoplasmic and transmembrane domains of the HPAIV HA protein. A single immunization of chickens with the chimeric VLP vaccine induced high levels of hemagglutination inhibition (HI) antibody titers against H5N1 HPAI virus and anti-NDV antibody detected in ELISA and protected chickens against subsequent lethal HPAIV and NDV infections. Furthermore, we could easily perform DIVA test using the commercial NP-cELISA tests against HPAIV and HI assay against NDV. These results strongly suggest that utilization of chimeric VLP vaccine in poultry species would be a promising strategy for the better control of HPAI and ND simultaneously. PMID:27626934

  16. Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA)

    PubMed Central

    Noh, Jin-Yong; Park, Jae-Keun; Lee, Dong-Hun; Yuk, Seong-Su; Kwon, Jung-Hoon; Lee, Sang-Won; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2016-01-01

    Highly pathogenic avian influenza (HPAI) and Newcastle disease (ND) are considered as the most devastating poultry infections, owing to their worldwide distribution and economical threat. Vaccines have been widely used to control these diseases in the poultry industry in endemic countries. However, vaccination policy without differentiating infected animals from vaccinated animals (DIVA) makes the virus surveillance difficult. In this study, we developed a bivalent virus-like particle (VLP) vaccine that is composed of the hemagglutinin (HA) and matrix 1 (M1) proteins of the H5N1 HPAI virus (HPAIV) and a chimeric protein containing the ectodomain of the ND virus (NDV) fusion (F) protein fused with the cytoplasmic and transmembrane domains of the HPAIV HA protein. A single immunization of chickens with the chimeric VLP vaccine induced high levels of hemagglutination inhibition (HI) antibody titers against H5N1 HPAI virus and anti-NDV antibody detected in ELISA and protected chickens against subsequent lethal HPAIV and NDV infections. Furthermore, we could easily perform DIVA test using the commercial NP-cELISA tests against HPAIV and HI assay against NDV. These results strongly suggest that utilization of chimeric VLP vaccine in poultry species would be a promising strategy for the better control of HPAI and ND simultaneously. PMID:27626934

  17. Macroscopic and Histological Evaluations of Meniscal Allograft Transplantation Using Gamma Irradiated Meniscus: A Comparative in Vivo Animal Study

    PubMed Central

    Zhang, Jin; Song, Guan-Yang; Chen, Xing-Zuo; Li, Yue; Li, Xu; Zhou, Jun-Lin

    2015-01-01

    higher ICRS scores and Mankin scores than both the 0 Mrad group and the 1.5 Mrad group (P < 0.05). Whereas the 1.5 Mrad group presented similar results to the 0 Mrad group concerning both the ICRS scores and the Mankin scores. Conclusions: The current in vivo animal study proved that although the meniscal collagen fibers were damaged after gamma irradiation, the failure rate of MAT surgeries might not significantly increase if the irradiation dose was <1.5 Mrad for New Zealand white rabbits. PMID:25963360

  18. Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator

    PubMed Central

    Mortazavi, SMJ; Mosleh-Shirazi, MA; Tavassoli, AR; Taheri, M; Mehdizadeh, AR; Namazi, SAS; Jamali, A; Ghalandari, R; Bonyadi, S; Haghani, M; Shafie, M

    2013-01-01

    The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response. PMID:23930107

  19. Change in permeability of the plasma membrane of blood cells in irradiated animals

    SciTech Connect

    Shevchenko, A.S.; Kobyalko, V.O.; Lazarev, N.M.; Aleksakhin, R.M.

    1994-11-01

    The Chernobyl nuclear disaster showed the exposure of the thyroid gland to radioactive iodine is an important factor of radiation damage to animals. Examination of domestic animals showed a marked inhibition of thyroid hormone secretion and changes in red cell membrane permeability for calcium in the absence of marked hematological shifts. At the same time the disturbed thyroid statis is associated with changes in some structural and functional parameters of blood cells. This research on calves shows that radiation damage to the thyroid produces a modifying effect on blood cell membrane permeability for calcium during both the acute and late periods following exposure to 131I. 15 refs., 2 figs., 1 tab.

  20. Lethal and sub-lethal effects of UVB on juvenile Biomphalaria glabrata (Mollusca: Pulmonata).

    PubMed

    Ruelas, Debbie S; Karentz, Deneb; Sullivan, John T

    2006-11-01

    Although Schistosoma mansoni occurs mainly in the tropics, where intense levels of solar radiation are present, the impact of ultraviolet (UV) light on schistosome transmission is not known. The purpose of this study was to investigate potential effects of UVB (290-320nm) on juvenile Biomphalaria glabrata, the snail intermediate host of S. mansoni. Albino and wild-type snails were exposed to doses of UVB from UV-fluorescent lamps, and the following were measured: survival, photoreactivation (light-mediated DNA repair), effects on feeding behavior, and morphological tissue abnormalities. Irradiation with UVB is lethal to B. glabrata in a dose-dependent manner. Exposure to white light subsequent to UVB irradiation enhances survival, probably by photoreactivation. The shell offers some, but not complete, protection. Experiments in which UVB transmittance through the shell was blocked with black nail polish suggest that injury to both exposed (headfoot) and shell-enclosed (mantle and visceral mass) tissues contributes to mortality in lethally irradiated snails. Wild-type (pigmented) snails are less susceptible to lethal effects of UVB than albino snails, and they may be more capable of photoreactivation. UVB exposure inhibits snail feeding behavior, and causes tentacle forks and growths on the headfoot. Thus, UVB may influence the life cycle of S. mansoni by both lethal and sub-lethal damage to the snail intermediate host. However, the ability of snails to photoreactivate may mitigate these effects. PMID:16996081

  1. Lethal and sub-lethal effects of UVB on juvenile Biomphalaria glabrata (Mollusca: Pulmonata).

    PubMed

    Ruelas, Debbie S; Karentz, Deneb; Sullivan, John T

    2006-11-01

    Although Schistosoma mansoni occurs mainly in the tropics, where intense levels of solar radiation are present, the impact of ultraviolet (UV) light on schistosome transmission is not known. The purpose of this study was to investigate potential effects of UVB (290-320nm) on juvenile Biomphalaria glabrata, the snail intermediate host of S. mansoni. Albino and wild-type snails were exposed to doses of UVB from UV-fluorescent lamps, and the following were measured: survival, photoreactivation (light-mediated DNA repair), effects on feeding behavior, and morphological tissue abnormalities. Irradiation with UVB is lethal to B. glabrata in a dose-dependent manner. Exposure to white light subsequent to UVB irradiation enhances survival, probably by photoreactivation. The shell offers some, but not complete, protection. Experiments in which UVB transmittance through the shell was blocked with black nail polish suggest that injury to both exposed (headfoot) and shell-enclosed (mantle and visceral mass) tissues contributes to mortality in lethally irradiated snails. Wild-type (pigmented) snails are less susceptible to lethal effects of UVB than albino snails, and they may be more capable of photoreactivation. UVB exposure inhibits snail feeding behavior, and causes tentacle forks and growths on the headfoot. Thus, UVB may influence the life cycle of S. mansoni by both lethal and sub-lethal damage to the snail intermediate host. However, the ability of snails to photoreactivate may mitigate these effects.

  2. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    SciTech Connect

    Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei

    2010-07-01

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  3. Dosimetry of a Small-Animal Irradiation Model using a 6 MV Linear Accelerator

    SciTech Connect

    Fitch, F. Moran; Martinez-Davalos, A.; Garcia-Garduno, O. A.

    2010-12-07

    A custom made rat-like phantom was used to measure dose distributions using a 6 MV linear accelerator. The phantom has air cavities that simulate the lungs and cylindrical inserts that simulate the backbone. The calculated dose distributions were obtained with the BrainScan v.5.31 TPS software. For the irradiation two cases were considered: (a) near the region where the phantom has two air cavities that simulate the lungs, and (b) with an entirely uniform phantom. The treatment plan consisted of two circular cone arcs that imparted a 500 cGy dose to a simulated lesion in the backbone. We measured dose distributions using EBT2 GafChromic film and an Epson Perfection V750 scanner working in transmission mode. Vertical and horizontal profiles, isodose curves from 50 to 450 cGy, dose and distance to agreement (DTA) histograms and Gamma index were obtained to compare the dose distributions using DoseLab v4.11. As a result, these calculations show very good agreement between calculated and measured dose distribution in both cases. With a 2% 2 mm criteria 100% of the points pass the Gamma test for the uniform case, while 98.9% of the points do it for the lungs case.

  4. Mycotoxin contamination of animal feedingstuff: detoxification by gamma-irradiation and reduction of aflatoxins and ochratoxin A concentrations.

    PubMed

    Di Stefano, Vita; Pitonzo, Rosa; Cicero, Nicola; D'Oca, Maria Cristina

    2014-01-01

    Mycotoxins are fungal secondary metabolites identified in many agricultural products screened for toxigenic moulds. They have been reported to be carcinogenic, teratogenic, tremorogenic, haemorrhagic and dermatitic to a wide range of organisms. With the increasing stringent regulations for mycotoxins imposed by importing countries such as those of the European Union, many cereals that are not safe for human consumption are used in formulations intended for animal feed. Gamma-rays are reported in the scientific literature to destroy ochratoxin A and aflatoxin in food crops and feed. The present study provides preliminary data for establishing the effect of dose of gamma-irradiation, ranging from 0 to 15 kGy, on aflatoxins and ochratoxin A reduction in commercial animal feed. The mycotoxin levels were determined by means of immunoaffinity clean-up (IAC) and HPLC with fluorescence detection (HPLC-FLD). The maximum reductions found at 15 kGy were 23.9%, 18.2%, 11.0%, 21.1% and 13.6% for ochratoxin A, aflatoxin B₁, aflatoxin B₂, aflatoxin G₁ and aflatoxin G₂, respectively. Results showed that the gamma-rays even at 15 kGy were not effective in the complete destruction of ochratoxin A and aflatoxins in the tested feed.

  5. SU-C-BRE-01: 3D Conformal Micro Irradiation Results of Four Treatment Sites for Preclinical Small Animal and Clinical Treatment Plans

    SciTech Connect

    Price, S; Yaddanapudi, S; Rangaraj, D; Izaguirre, E

    2014-06-15

    Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the image guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and iteratively

  6. Misonidazole and potentially lethal damage

    SciTech Connect

    Korbelik, M.; Palcic, B.; Skov, K.; Skarsgard, L.

    1982-03-01

    The existence of potentially lethal damage (PLD) is demonstrated in exponentially growing CHO cells exposed to misonidazole in hypoxia. The method of hypertonic post-treatment of cells was used in these studies. Misonidazole-induced PLD differs in many characteristics from radiation-induced PLD.The repair kinetics of misonidazole-induced PLD are much slower than for the repair of radiation-induced PLD (hours vs. minutes). No significant repair of misonidazole-induced PLD took place at 25/sup 0/C. Other differences are discussed. Hypertonic post-treatment of irradiated cells which had been pre-incubated with misonidazole to non-toxic levels, gave survival data consistent with the interpretation that no radiation PLD can be induced in such cells.

  7. Long-lived radicals produced by γ-irradiation or vital activity in plants, animals, cells, and protein solution: their observation and inhomogeneous decay dynamics

    NASA Astrophysics Data System (ADS)

    Miyazaki, Tetsuo; Morikawa, Akiyuki; Kumagai, Jun; Ikehata, Masateru; Koana, Takao; Kikuchi, Shoshi

    2002-09-01

    Long-lived radicals produced by γ-irradiation or vital activity in plants, animals, cells, and protein (albumin) solution were studied by electron spin resonance spectroscopy. Long-lived radicals produced by vital activity exist in biological systems, such as plants, animals, and cells, in the range of 0.1-20 nmol g -1. Since vital organs keep the radicals at a constant concentration, the radicals are probably related to life conservation. Long-lived radicals are also produced by γ-irradiation of cells or protein solution. The radicals decay after death of living things or after γ-irradiation. We found that the decay dynamics in all biological systems can be expressed by the same kinetic equation of an inhomogeneous reaction.

  8. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    SciTech Connect

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A

  9. In vivo 3D analysis of systemic effects after local heavy-ion beam irradiation in an animal model

    PubMed Central

    Nagata, Kento; Hashimoto, Chika; Watanabe-Asaka, Tomomi; Itoh, Kazusa; Yasuda, Takako; Ohta, Kousaku; Oonishi, Hisako; Igarashi, Kento; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Nishimaki, Toshiyuki; Katsumura, Takafumi; Oota, Hiroki; Ogawa, Motoyuki; Oga, Atsunori; Ikemoto, Kenzo; Itoh, Hiroshi; Kutsuna, Natsumaro; Oda, Shoji; Mitani, Hiroshi

    2016-01-01

    Radiotherapy is widely used in cancer treatment. In addition to inducing effects in the irradiated area, irradiation may induce effects on tissues close to and distant from the irradiated area. Japanese medaka, Oryzias latipes, is a small teleost fish and a model organism for evaluating the environmental effects of radiation. In this study, we applied low-energy carbon-ion (26.7 MeV/u) irradiation to adult medaka to a depth of approximately 2.2 mm from the body surface using an irradiation system at the National Institutes for Quantum and Radiological Science and Technology. We histologically evaluated the systemic alterations induced by irradiation using serial sections of the whole body, and conducted a heart rate analysis. Tissues from the irradiated side showed signs of serious injury that corresponded with the radiation dose. A 3D reconstruction analysis of the kidney sections showed reductions in the kidney volume and blood cell mass along the irradiated area, reflecting the precise localization of the injuries caused by carbon-beam irradiation. Capillary aneurysms were observed in the gill in both ventrally and dorsally irradiated fish, suggesting systemic irradiation effects. The present study provides an in vivo model for further investigation of the effects of irradiation beyond the locally irradiated area. PMID:27345436

  10. 78 FR 27303 - Irradiation in the Production, Processing, and Handling of Animal Feed and Pet Food; Electron...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-10

    ... Feed and Pet Food; Electron Beam and X-Ray Sources for Irradiation of Poultry Feed and Poultry Feed... safe use of electron beam and x-ray sources for irradiation of poultry feed and poultry feed... CFR part 579) to provide for the safe use of electron beam and x-ray sources for irradiation...

  11. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates

    PubMed Central

    Krivokrysenko, Vadim I.; Toshkov, Ilia A.; Gleiberman, Anatoli S.; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K.; Narizhneva, Natalya V.; Singh, Vijay K.; Whitnall, Mark H.; Purmal, Andrei A.; Shakhov, Alexander N.; Gudkov, Andrei V.; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  12. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    PubMed

    Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  13. Large animal normal tissue tolerance with boron neutron capture

    SciTech Connect

    Gavin, P.R.; Swartz, C.D. ); Kraft, S.L. ); Briebenow, M.L. ); DeHaan, C.E.

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA[sub 2]B[sub 12]H[sub 11]SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 [times] 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs.

  14. Potentially-lethal damage and radioprotection in human cells exposed to californium-252

    SciTech Connect

    Schroy, C.B.; Goud, S.N.; Magura, C.; Feola, J.M.; Maruyama, Y.

    1986-01-01

    Cultured human T-1E cells were irradiated with californium-252 neutrons and gamma rays. When 2 mm caffeine was present in the medium for 47 h after irradiation cell survival (assayed by colony formation) was decreased significantly. When 2 m dimethylsulfoxide was present during the irradiations radioprotection was observed using the same assay. The caffeine data indicate that potentially-lethal lesions exist in cells after californium exposure and that these lesions can be made lethal when they would otherwise be repaired. The DMSO data indicate that radioprotection from californium exposure can be achieved and that scanvengable free radicals play an important role in Cf-252 lethality.

  15. Effects of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing.

    PubMed

    Silveira, Paulo Cesar Lock; Silva, Luciano A; Freitas, Tiago P; Latini, Alexandra; Pinho, Ricardo A

    2011-01-01

    Gallium-arsenide (GaAs) and helium-neon (HeNe) lasers are the most commonly used low-energy lasers in physiotherapy for promoting wound healing and pain modulation. The aim of this study was investigate the effect of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. The animals were randomly divided into five groups (n=6): Controls (skin injured animals without local or systemic treatment), skin injury treated with HeNe 1 J/cm(2) (two seg); skin injury treated with HeNe 3 J/cm(2) (six seg); skin injury treated with GaAs 1 J/cm(2) (three seg); skin injury treated with GaAs 3 J/cm(2) (nine seg). A single circular wound measuring 8 mm in diameter was surgically created on the back of the animal. The rats were irradiated at 2, 12, 24, 48, 72, 96, and 120 h after skin injury. The parameters, namely hydroxyproline content, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and lipid (TBARS) and protein oxidation (carbonyl groups) measurements were assessed. In addition, wound size regression was also analyzed. The results showed an improvement in the wound healing reflected by the reduction in wound size and increased collagen synthesis. Moreover, a significant reduction in TBARS levels, carbonyl content, and SOD and CAT activities were observed after laser irradiation, particularly with the treatments HeNe laser 1 and 3 J/cm(2) dose and GaAs 3 J/cm(2) dose. The data strongly indicate that LPLI therapy is efficient in accelerating the skin wound healing process after wounding, probably by reducing the inflammatory phase and inducing collagen synthesis.

  16. Effects of UV-C irradiation on phosphoinositide turnover in plant cells: similarities with those occurring via the formation of reactive oxygen intermediates in animal cells.

    PubMed

    Piacentini, M P; Ricci, D; Fraternale, D; Piatti, E; Manunta, A; Accorsi, A

    1999-03-01

    With the aim of examining the response of plant cells to UV-C irradiation, we investigated the behaviour of the phosphatidylinositol 4,5 bisphosphate (PtdIns 4,5-P2) molecule (the precursor of the phosphoinositide signal transduction cascade) by exposing callus cells from Peucedanum verticillare to UV-C (130 J m-2) and by examining the level and the fatty acid composition of PtdIns 4,5-P2 at different times after irradiation. We show that a pathway for the UV-C response includes transient PtdIns 4,5-P2 breakdown. The effect of ultraviolet rays is mimicked by H2O2 suggesting that in this plant it may be brought about by reactive oxygen intermediates (ROI), as already underlined in experimental animal models. PMID:10374257

  17. Lethal entanglement in baleen whales.

    PubMed

    Cassoff, Rachel M; Moore, Kathleen M; McLellan, William A; Barco, Susan G; Rotsteins, David S; Moore, Michael J

    2011-10-01

    Understanding the scenarios whereby fishing gear entanglement of large whales induces mortality is important for the development of mitigation strategies. Here we present a series of 21 cases involving 4 species of baleen whales in the NW Atlantic, describing the available sighting history, necropsy observations, and subsequent data analyses that enabled the compilation of the manners in which entanglement can be lethal. The single acute cause of entanglement mortality identified was drowning from entanglement involving multiple body parts, with the animal's inability to surface. More protracted causes of death included impaired foraging during entanglement, resulting in starvation after many months; systemic infection arising from open, unresolved entanglement wounds; and hemorrhage or debilitation due to severe gear-related damage to tissues. Serious gear-induced injury can include laceration of large vessels, occlusion of the nares, embedding of line in growing bone, and massive periosteal proliferation of new bone in an attempt to wall off constricting, encircling lines. These data show that baleen whale entanglement is not only a major issue for the conservation of some baleen whale populations, but is also a major concern for the welfare of each affected individual.

  18. Perinatal lethal osteogenesis imperfecta.

    PubMed Central

    Cole, W G; Dalgleish, R

    1995-01-01

    Perinatal lethal osteogenesis imperfecta is the result of heterozygous mutations of the COL1A1 and COL1A2 genes that encode the alpha 1(I) and alpha 2(I) chains of type I collagen, respectively. Point mutations resulting in the substitution of Gly residues in Gly-X-Y amino acid triplets of the triple helical domain of the alpha 1(I) or alpha 2(I) chains are the most frequent mutations. They interrupt the repetitive Gly-X-Y structure that is mandatory for the formation of a stable triple helix. Most babies have their own private de novo mutation. However, the recurrence rate is about 7% owing to germline mosaicism in one parent. The mutations act in a dominant negative manner as the mutant pro alpha chains are incorporated into type I procollagen molecules that also contain normal pro alpha chains. The abnormal molecules are poorly secreted, more susceptible to degradation, and impair the formation of the extracellular matrix. The collagen fibres are abnormally organised and mineralisation is impaired. The severity of the clinical phenotype appears to be related to the type of mutation, its location in the alpha chain, the surrounding amino acid sequences, and the level of expression of the mutant allele. Images PMID:7643358

  19. Recovery of microorganisms from potentially lethal radiation damage

    NASA Astrophysics Data System (ADS)

    Borsa, Joseph; Lucht, Lisa; Blank, Greg

    1995-02-01

    Dose response curves for inactivation of microorganisms are central in the design of any process intending to use irradiation for the improvement of the microbiological quality of any treated materials, be it food or medical supplies. Under some conditions a fraction of irradiated microorganisms is able to recover from a potentially lethal dose. This recovery phenomenon must be considered in determining the efficacy of irradiation in microbial inactivation. In this work the recovery phenomenon was examined in eleven species of microorganisms. Variables examined included dose, radiation type, post-irradiation holding temperature, and nutritient medium used to culture the organism. Kinetics of damage repair and fixation were also examined. Results indicate that, for certain species of microorganisms, recovery can significantly lower the killing efficacy of irradiation.

  20. Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.).

    PubMed

    Samarth, R M; Goyal, P K; Kumar, Ashok

    2004-07-01

    The radioprotective effects of Mentha oil (Mentha piperita Linn.) against radiation induced haematological alterations in peripheral blood and the survival of Swiss albino mice were studied. Mentha oil 40 micro L/animal/day for 3 consecutive days when fed orally prior to whole-body gamma irradiation (8 Gy) showed protection of the animals in terms of the survival percentage and haematological parameters in mice. Fifty per cent of the animals died within 20 days and 100% mortality was observed up to 30 days post-irradiation in the control irradiated group. Whereas only 17% of the mice died within 30 days in the experimental group (Mentha oil pretreated irradiated). The total RBC count decreased maximally at 24 h (3.45 +/- 0.20 x 10(12)/L, p < 0.001), similar observations were obtained for the WBC count, haemoglobin content and haematocrit percentage in the irradiated control animals. However, in irradiated animals pretreated with Mentha oil, although the initial values of haematological components were lower they later showed a remarkable recovery reaching normal at 30 days post-irradiation compared with the irradiated control animals. In general, the recovery of the blood cell number in irradiated animals depends on the survival of stem cells and their derivatives. The results from the present study suggest that the oil of Mentha piperita (Linn.) has a radioprotective role in stimulating/protecting the haematopoietic system. Hence, enhanced survival and an increase in the haematological constituents of peripheral blood of mice against lethal gamma radiation was observed.

  1. Sanitation of selected ready-to-eat intermediate-moisture foods of animal origin by E-beam irradiation.

    PubMed

    Cambero, María I; Cabeza, María C; Escudero, Rosa; Manzano, Susana; Garcia-Márquez, Irene; Velasco, Raquel; Ordóñez, Juan A

    2012-07-01

    To optimize the sanitation treatment of ready-to-eat (RTE) intermediate-moisture foods (IMF), the behavior of Listeria monocytogenes Scott A (CIP 103575), L. innocua (NTC 11288), Salmonella enterica serovar Typhimurium (CECT 443), and Escherichia coli O157:H7 (CECT 4972) following treatment with electron-beam irradiation has been studied. As food matrixes, three RTE vacuum-packed products (Iberian dry-cured ham, dry beef [cecina], and smoked tuna) were used. Although an irradiation treatment is not necessary when the 10(2) colony-forming units/g microbiological criterion for L. monocytogenes is applied, a treatment of 1.5 kGy must be applied to IMFs to meet the food safety objective in the case of the "zero tolerance" criterion for the three strains. The IMF products presented negligible modifications of color (L*, a*, and b*), sensory (appearance, odor, and flavor), and rheology (hardness, springiness, adhesiveness, cohesiveness, gumminess, chewiness, and breaking strength) parameters at doses lower than 2 kGy. Therefore, the treatment of 1.5 kGy warrants safe IMF with sensory properties similar to those of the genuine products.

  2. The combination of the active principles of Podophyllum hexandrum supports early recovery of the gastrointestinal system via activation of Nrf2-HO-1 signaling and the hematopoietic system, leading to effective whole-body survival in lethally irradiated mice.

    PubMed

    Dutta, A; Gupta, M L; Kalita, B

    2015-03-01

    This study is aimed at the development of a safe radioprotective formulation to minimize human sufferings during accidental nuclear exposures. In the current study, a combination of three active principles, namely podophyllotoxin, podophyllotoxin beta-D-glucoside, and rutin (G-002M), isolated from Podophyllum hexandrum rhizomes, has been evaluated for its radioprotective potential and mode of action. Total body protection studies have demonstrated that a single prophylactic dose of G-002M delivered more than 85% survival in mice exposed to a lethal (9 Gy) dose of gamma radiation, and significantly protected the radiosensitive hematopoietic and gastrointestinal organs. Studies have also revealed a reduction in free radical generation, lipid peroxidation, protein carbonylation, and cell death in mouse intestine after G-002M treatment, while GSH was observed to be enhanced in the same tissue. Redox-sensitive transcription factor (Nrf2) activation and subsequent upregulation of heme oxygenase-1 (HO-1) and SOD-1 revealed the cytoprotective role of G-002M. A histological examination of the jejunum pretreated with the formulation also demonstrated less damage to the villi, crypts, and the mucosal layers. These observations reiterated that the reduction in the ROS levels, protection of cellular macromolecules, and activation of the antioxidant signaling pathway may have been the principle factors involved in G-002M- mediated protection against radiation-induced tissue impairment. The potentially safe and effective radioprotective characteristics of this new combination are encouraging for further studies for human application.

  3. Irradiated homologous tarsal plate banking: A new alternative in eyelid reconstruction. Part I. Technique and animal research

    SciTech Connect

    Jordan, D.R.; Tse, D.T.; Anderson, R.L.; Hansen, S.O. )

    1990-01-01

    Reconstruction of full thickness eyelid defects requires the correction of both posterior lamella (tarsus, conjunctiva) and anterior lamella (skin, muscle). Tarsal substitutes including banked sclera, nasal cartilage, ear cartilage, and periosteum can be beneficial for posterior lamellar repair, while anterior lamellar replacement, including skin grafts, pedicle flaps, advancement flaps, etc., is important to cover the posterior reconstructed portion. At times, due to extensive tissue loss, the eyelid reconstruction can be particularly challenging. We have found an alternative posterior lamellar reconstructive technique utilizing irradiated homologous tarsal plate that can be particularly useful in selected cases of severe tissue loss. The experimental surgical procedure in monkeys and the histological fate of the implanted tarsus is described in Part I, and followed in Part II by our experience with this tissue in six human patients.

  4. The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

    PubMed Central

    Cross, Robert W.; Mire, Chad E.; Borisevich, Viktoriya; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo. PMID:27354371

  5. [Anorexia in rats following protracted whole-body irradiation with low doses].

    PubMed

    Schraub, A; Sattler, E L; Döll, G; Kindt, A

    1975-07-01

    In our experiments, carried out hitherto, concerning the effect of incorporated and radioactive substances, weight behaviour and food uptake have proved to be a sensitive test. With regard to these experiments and the half-life of the radionuclides used, it is reported about trial series in Wistar rats. These rats were applied, with Co-60 gamma irradiation, different whole-body doses protracted over 48 hours. A total of 32 groups of experimental animals (20 animals each) was exposed to irradiation doses of lethal, medium lethal, and sublethal ranges, control and pseudo-irradiation series included. The experiments were carried out under observance of constant irradiation and attitude conditions, night and day changes, as conditioned by the season, included. Even in the inferior sublethal range (12 to 24 R), a significant trend of decreased food uptake is registered. This trend remains for a short period after the end of irradiation, but then it returns to normal conditions. Furthermore, a new decrease with subsequent increase seems to become evident-about ten days after termination of the radiotherapy (especially after several hundred R); report about these items will be made later on.

  6. Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

    PubMed

    Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

    2016-01-01

    RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

  7. Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

  8. Biological effects of ultraviolet irradiation on bees

    SciTech Connect

    Es`kov, E.K.

    1995-09-01

    The influence of natural solar and artificial ultraviolet irradiation on developing bees was studied. Lethal exposures to irradiation at different stages of development were determined. The influence of irradiation on the variability of the morphometric features of bees was revealed. 5 refs., 1 fig.

  9. Uses of irradiation for inactivation of microorganisms

    SciTech Connect

    Brynjolfsson, A.

    1988-01-01

    The lethal effects of radiation on microorganisms was noted soon after the discovery of X rays in 1895. In 1904, it was shown that vegetative bacteria are more sensitive than spores; however, no industrial applications could be made as the radiation sources were too expensive. In the mid-1950s, it became economical and practical to sterilize medical products, and ever since sterilization has been a growing industry. Radiation sterilization technology has made possible users of new materials, such as plastics. Food irradiation is about to take off. Just as there was a resistance to pasteurization of milk when it was first introduced, there will be resistance to radpasteurization. Irradiated foods have been proven safe beyond reasonable doubt. Safety has been established through two independent methods: (1) through the most extensive multigeneration animal feeding studies ever carried out, and (2) by analyzing the radiolytic products formed and the chemical changes that take place when food is irradiated. The possible toxicity of these products has been evaluated by an independent group of toxicologists, who based their evaluation on the results of exposure of these products in large quantities either to humans or to animals.

  10. [The "lethal white foal" syndrome].

    PubMed

    Blendinger, C; Müller, G; Bostedt, H

    1994-06-01

    The lethal white foal syndrome (congenital intestinal aganglionosis) was diagnosed by history, clinical signs and pathological findings in a female foal, born in March 1992, that was an offspring of two overo-spotted paint horses. The syndrome is a congenital innervation defect of the gastrointestinal tract. A literature review of this condition, relatively unknown in Germany, is given.

  11. Subcutaneous wounding postirradiation reduces radiation lethality in mice.

    PubMed

    Garrett, Joy; Orschell, Christie M; Mendonca, Marc S; Bigsby, Robert M; Dynlacht, Joseph R

    2014-06-01

    The detonation of an improvised nuclear device during a radiological terrorist attack could result in the exposure of thousands of civilians and first responders to lethal or potentially lethal doses of ionizing radiation (IR). There is a major effort in the United States to develop phamacological mitigators of radiation lethality that would be effective particularly if administered after irradiation. We show here that giving female C57BL/6 mice a subcutaneous surgical incision after whole body exposure to an LD50/30 X-ray dose protects against radiation lethality and increases survival from 50% to over 90% (P = 0.0001). The increase in survival, at least in part, appears to be due to enhanced recovery of hematopoiesis, notably red blood cells, neutrophils and platelets. While a definitive mechanism has yet to be elucidated, we propose that this approach may be used to identify potentially novel mechanisms and pathways that could aid in the development of novel pharmacological radiation countermeasures. PMID:24811864

  12. Effects of laser irradiation at different wavelengths (660, 810, 980, and 1,064 nm) on mucositis in an animal model of wound healing.

    PubMed

    Usumez, Aslihan; Cengiz, Beyhan; Oztuzcu, Serdar; Demir, Tuncer; Aras, Mutan Hamdi; Gutknecht, Norbert

    2014-11-01

    The aim of the present study was to compare the effectiveness of four different laser wavelengths (660, 810, 980, and 1,064 nm) used for low-level laser therapy (LLLT) on the healing of mucositis in an animal model of wound healing by investigating the expression of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and blood-derived fibroblast growth factor (bFGF). Thirty-five male Wistar albino rats with a weight of 250-300 g body mass and 5 months old were used in the study. All animals were intraperitoneally injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tip of an 18-gauge needle was used in order to develop a superficial scratching on the left cheek pouch mucosa by dragging twice in a linear movement on third and fifth days. After ulcerative mucositis were clinically detected on the animals' left cheek pouch mucosa, the laser therapy was started. Four different laser wavelengths (660 nm, HELBO, Bredent; 810 nm, Fotona XD, Fotona; 980 nm, ARC Fox; and 1,064 nm, Fidelis Plus 3, Fotona) used for LLLT at ED 8 J/cm(2) daily from the first to the fourth days. Oval excisional biopsy was taken from the site of the wound, and the expression of PDGF, TGF-β, and bFGF was evaluated. The obtained data were analyzed by one2-way ANOVA, and then Tukey HSD tests were used for pairwise comparisons among groups (α = 0.05). The one-way ANOVA test indicated that expression values of the growth factors, PDGF and bFGF, were significantly affected by irradiation of different wavelengths of lasers (p < 0.001). However, expression value of the TGF-β was not affected by irradiation of different wavelengths of lasers (p > 0.05). The highest PDGF expression was detected in neodymium-doped yttrium aluminum garnet (Nd:YAG) laser group (p < 0.05), and there were no statistically significant differences among the other groups (p > 0.05). The highest bFGF expression was detected

  13. Lethal mutagenesis and evolutionary epidemiology.

    PubMed

    Martin, Guillaume; Gandon, Sylvain

    2010-06-27

    The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy.

  14. The repair of sub-lethal damage and the stimulated repair of potentially lethal damage in Saintpaulia.

    PubMed

    Leenhouts, H P; Sijsma, M J; Litwiniszyn, M; Chadwick, K H

    1981-10-01

    The repair of sublethal and potentially lethal damage in stationary resting epidermal cells of Saintpaulia has been investigated. Fractionation experiments reveal an efficient repair of sublethal damage with a half-life of 1.9 hours. No repair of potentially lethal damage was noted when cultivation of the leaves was delayed for 24 hours after irradiation. At delay times of 2, 3 and 4 days some repair of potentially lethal damage has been found. A small pre-dose given 24 hours before a challenging dose improved the cells' chance to regenerate and the improvement has been shown to be compatible with an improved repair of potentially lethal damage induced by X-rays and fast neutrons. It hs been shown that the stimulated repair process takes 12 to 24 hours to develop, is dependent on the size of the pre-dose, has single-hit dose kinetics, and an r.b.e. of 1 for neutrons. With delayed cultivation of 2 days the stimulated repair process leads to an alteration in the shape of the regeneration (survival)-dose relationship which increases the low dose r.b.e. for neutrons from 10 to 35. PMID:6975252

  15. Clostridium sordellii Lethal Toxin Kills Mice by Inducing a Major Increase in Lung Vascular Permeability

    PubMed Central

    Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R.

    2007-01-01

    When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication. PMID:17322384

  16. Vocal Fold Augmentation with Beta Glucan Hydrogel Cross-Linked by γ Irradiation for Enhanced Duration of Effect: In Vivo Animal Study

    PubMed Central

    Lim, Youn-Mook; Kim, Bo Hae; Kim, Hee-Bok; Park, EunJi; Park, Seok-Won; Park, Jong-Seok; Choi, Se In; Kwon, Tack-Kyun; Kwon, Seong Keun

    2015-01-01

    This study explored a novel strategy to restore the vocal gap by using cross-linked β-glucan hydrogel by γ-irradiation. An aqueous solution of 5 wt% β-glucan was prepared and cross-linked using 60Co γ irradiation. Ten nude mice were injected with 0.8 mL of irradiated β-glucan on the left back and the same volume of nonirradiated β-glucan on the right back for comparison. The mice were sacrificed at 1 and 2 weeks after injection and histological evaluations were performed. Irradiated β-glucan demonstrated a significantly larger volume than nonirradiated β-glucan in the back of nude mice with less inflammatory reaction. After unilateral recurrent laryngeal nerve section in New Zealand White rabbits, irradiated and nonirradiated β-glucan were injected into paralyzed vocal folds. Irradiated β-glucan remained at the paralyzed vocal fold without definite inflammatory signs on endoscopy. High-speed recordings of vocal fold vibration showed decreased vocal gap in irradiated group compared to nonirradiated group. Histologically, the laryngeal epithelium and lamina propria remained intact, without inflammatory cell infiltration. Our newly developed injection material, irradiated β-glucan, showed excellent biocompatibility and remained longer than nonirradiated β-glucan in vivo, suggesting irradiated hydrogels as a new therapeutic approach that may be useful for the long-term treatment of vocal fold palsy. PMID:26858956

  17. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  18. LETHAL LEVELS OF HYPOXIA FOR GULF COAST ESTUARINE ANIMALS

    EPA Science Inventory

    There is increasing concern about eutrophication and subsequent hypoxia problems in estuaries. The U.S. Environmental Protection Agency has developed Water Quality Criteria (WQC) for dissolved oxygen (DO) in saltwater for Cape Cod, MA to Cape Hatteras, NC but inadequate data exis...

  19. Electroshock weapons can be lethal!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  20. Arenavirus extinction through lethal mutagenesis.

    PubMed

    de la Torre, Juan Carlos

    2005-02-01

    Viral hemorrhagic fevers represent serious human public health problems causing devastating and often lethal disease. Several hemorrhagic fevers are caused by arenaviruses including Lassa fever virus (LFV) and the South American viral hemorrhagic fevers (SAHF). In recent years, increased air travel between Africa and other areas has led to the importation of LFV into the US, Europe, Japan, and Canada. This has raised awareness about arenaviruses as potential emerging viruses. Moreover, because of its severe morbidity and high mortality, and transmissibility from human to human, weaponized forms of LFV poses a real threat as agent of bioterrorism. No licensed vaccine is available in the US, and currently there is not efficacious therapy to treat these infections. Therefore, the importance of developing novel effective antiviral drugs to combat HF arenaviruses, for which the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) provides us with an excellent model system. Recent findings have shown that LCMV multiplication both in cultured cells and in vivo is highly susceptible to the mutagenic agent 5-fluorouracil (FU). FU-mediated extinction of LCMV was associated with only modest increases in virus mutation frequencies, but did not significantly affect virus replication and transcription, or virus particle formation. These findings indicate that, as with other riboviruses, lethal mutagenesis is effective also against LCMV raising the possibility of using this novel antiviral strategy to combat pathogenic arenaviruses. PMID:15649566

  1. Protective effects of kojic acid on the periphery blood and survival of beagle dogs after exposure to a lethal dose of gamma radiation.

    PubMed

    Wang, Kai; Li, Peng-Fei; Han, Chun-Guang; Du, Li; Liu, Chao; Hu, Ming; Lian, Shi-Jie; Liu, Yong-Xue

    2014-12-01

    In previous studies, it has been shown that pretreatment with kojic acid (KA) not only increased the 30 day survival rate of mice after exposed to a lethal dose of gamma radiation but also had significant radioprotective effects on the hematopoietic system, the immune system and DNA of mice exposed to a 4 Gy sublethal dose of radiation. Furthermore, pretreatment with KA has also been shown to protect Chinese hamster ovary (CHO) cells against ionizing radiation-induced damage. In this investigation, beagle dogs were used to evaluate whether KA could also be radioprotective in a large animal model. Dogs in the group pretreated with kojic acid after whole-body exposure to a lethal dose of 3 Gy gamma radiation had a 51 day survival rate of 66.7% versus the dogs in the 3 Gy irradiation only group, which all died within 16 days of postirradiation. General vital signs (body weight or temperature) of animals in the kojic acid pretreated group reduced and increased maximally at day 14 postirradiation and then reverted to normal levels gradually. The hematopoiesis studies indicated that the white blood cells/red blood cells, hemoglobin content and hematocrit of dogs pretreated with kojic acid decreased sharply at day 23/day 21 postirradiation, and then gradually elevated. In addition, the DNA content of dogs pretreated with KA were significantly increased compared with that of dogs in the irradiation group at day 4 postirradiation and the number of micronuclei in the group pretreated with kojic acid declined sharply compared with that of the irradiation only group. KA appears to possess marked protective effects from radiation-induced damage and therefore, may be a promising novel radioprotective agent.

  2. Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation.

    PubMed

    Farese, Ann M; Hankey, Kim G; Cohen, Melanie Veirs; MacVittie, Thomas J

    2015-11-01

    Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described, which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose, 0.13 Gy min), resulting in an approximate LD10/60 (n = 5/59). Animals received medical management, and hematopoietic and immune cell recovery was assessed (n ≤ 14) through 370 d post exposure. A subset of animals (n ≤ 8) was examined through 700 d. Myeloid recovery was assessed by neutrophil and platelet-related parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were identified by T cell receptor excision circle quantification. Severe neutropenia, lymphopenia, and thrombocytopenia resolved within 30 d. Total CD3+ cells μL required 60 d to reach values 60% of normal, followed by subsequent slow recovery to approximately normal by 180 d post irradiation. Recovery of CD3+4+ and CD3+8+ cell memory and naïve subsets were markedly different. Memory populations were ≥ 100% of normal by day 60, whereas naïve populations were only 57% normal at 180 d and never fully recovered to baseline post irradiation. Total (CD20+) B cells μL were within normal levels by 77 d post exposure. This animal model elucidates the variable T- and B-cell subset recovery kinetics after a potentially lethal dose of total-body irradiation that are dependent on marrow-derived stem and progenitor cell recovery, peripheral homeostatic expansion, and thymopoiesis.

  3. Development of synthetic lethality anticancer therapeutics.

    PubMed

    Fang, Bingliang

    2014-10-01

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy.

  4. Effects of laser irradiation at different wavelengths (660, 810, 980, and 1064 nm) on transient receptor potential melastatin channels in an animal model of wound healing.

    PubMed

    Isman, Eren; Aras, Mutan Hamdi; Cengiz, Beyhan; Bayraktar, Recep; Yolcu, Umit; Topcuoglu, Tolga; Usumez, Aslihan; Demir, Tuncer

    2015-07-01

    The aim of the present study was to compare the effectiveness of four different laser wavelengths used for low-level laser therapy(LLLT) on healing of mucositis in an animal model of wound healing, by investigating expression of transient receptor potential melastatin(TRPM) ion channels. Forty-five rats were intraperitoneally injected with 100 mg/kg 5-fluorouracil on day 1 and 65 mg/kg on day 3. Superficial scratching on left cheek pouch mucosa was performed on days 3 and 5. After ulcerative mucositis was clinically detected, LLLT was started (660 nm, HELBO; 810 nm, Fotona-XD; 980 nm, ARC-Fox; and 1064 nm, Fidelis-Plus3) at 8 J/cm(2)/day from days 1 to 4. Oval excisional biopsy was performed at the wound site, and expression of TRPM2 to TRPM8 was evaluated. Student's t test was used for evaluation of significance of TRPM gene expression according to "0" value (α = 0.05). In 980-nm group, TRPM4, TRPM6, and TRPM7 were significantly higher than in the control group (p < 0.005). In 660, 810, and 1064 nm groups, only TRPM6 was significantly higher than in control group (p < 0.005). There were no significant differences between control and sham groups (p > 0.05). These findings suggest that expression of TRPM6 gene was significantly affected by irradiation with lasers at different wavelengths, whereas the TRPM4 and TRPM7 genes were only expressed in the 980-nm diode laser group. TRPM6 gene was highly expressed during LLLT, which may lead to accelerated wound healing and tissue repair. In contrast, there was some evidence that the 980-nm diode laser caused increased expression of TRPM4, TRPM6, and TRPM7 which are responsible for stimulation of Ca(2+) and Mg(2+) metabolism, as well as apoptotic pathways of controlled cell death. PMID:25863514

  5. A multivariate model of stakeholder preference for lethal cat management.

    PubMed

    Wald, Dara M; Jacobson, Susan K

    2014-01-01

    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n=1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI=0.94, RMSEA=0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.

  6. A Multivariate Model of Stakeholder Preference for Lethal Cat Management

    PubMed Central

    Wald, Dara M.; Jacobson, Susan K.

    2014-01-01

    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n = 1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI = 0.94, RMSEA = 0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management. PMID:24736744

  7. The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

    PubMed

    Farese, Ann M; Brown, Cassandra R; Smith, Cassandra P; Gibbs, Allison M; Katz, Barry P; Johnson, Cynthia S; Prado, Karl L; MacVittie, Thomas J

    2014-01-01

    The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells μL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

  8. Simulation and optimization of pulsed radio frequency (RF) irradiation scheme for chemical exchange saturation transfer (CEST) MRI – demonstration of pH-weighted pulsed-amide proton CEST MRI in an animal model of acute cerebral ischemia

    PubMed Central

    Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S.; Zhang, Xiaoan; Benner, Thomas; Sorensen, A Gregory

    2011-01-01

    Chemical exchange saturation transfer (CEST) MRI is capable of measuring dilute labile protons and microenvironment properties; however, the CEST contrast is also dependent upon experimental conditions, particularly, the RF irradiation scheme. Although continuous-wave (CW) RF irradiation has been conventionally utilized, the RF pulse duration or duty cycle are limited on most clinical systems, for which pulsed RF irradiation must be chosen. Here, conventional numerical simulation was extended to describe pulsed-CEST MRI contrast as a function of RF pulse parameters (i.e., RF pulse duration and flip angle) and labile proton properties (i.e., exchange rate and chemical shift). For diamagnetic CEST agents undergoing slow/intermediate chemical exchange, our simulation showed a linear regression relationship between the optimal mean RF power for pulsed-CEST MRI and that of CW-CEST MRI. Worth noting, the optimized pulsed-CEST contrast was approximately equal to that of CW-CEST MRI for exchange rates below 50 s−1, as confirmed experimentally using a multi-compartment pH phantom. Moreover, acute stroke animals were imaged with both pulsed- and CW- amide protons CEST MRI, which showed similar contrast. In summary, our study elucidated the RF irradiation dependence of pulsed-CEST MRI contrast, providing useful insights to guide its experimental optimization and quantification. PMID:21437977

  9. Inhibitors of the Metalloproteinase Anthrax Lethal Factor.

    PubMed

    Goldberg, Allison B; Turk, Benjamin E

    2016-01-01

    Bacillus anthracis, a rod shaped, spore forming, gram positive bacteria, is the etiological agent of anthrax. B. anthracis virulence is partly attributable to two secreted bipartite protein toxins, which act inside host cells to disrupt signaling pathways important for host defense against infection. These toxins may also directly contribute to mortality in late stage infection. The zinc-dependent metalloproteinase anthrax lethal factor (LF) is a critical component of one of these protein toxins and a prime target for inhibitor development to produce anthrax therapeutics. Here, we describe recent efforts to identify specific and potent LF inhibitors. Derivatization of peptide substrate analogs bearing zinc-binding groups has produced potent and specific LF inhibitors, and X-ray crystallography of LFinhibitor complexes has provided insight into features required for high affinity binding. Novel inhibitor scaffolds have been identified through several approaches, including fragment-based drug discovery, virtual screening, and highthroughput screening of diverse compound libraries. Lastly, efforts to discover LF inhibitors have led to the development of new screening strategies, such as the use of full-length proteins as substrates, that may prove useful for other proteases as well. Overall, these efforts have led to a collection of chemically and mechanistically diverse molecules capable of inhibiting LF activity in vitro and in cells, as well as in animal models of anthrax infection. PMID:27072692

  10. Alcohol Consumption and Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

    Powell, Kenneth E.; Kresnow, Marcie-jo; Mercy, James A.; Potter, Lloyd B.; Swann, Alan C.; Frankowski, Ralph F.; Lee, Roberta K.; Bayer, Timothy L.

    2002-01-01

    Presents a case-control study of the association between nearly lethal suicide attempts and facets of alcohol consumption; namely, drinking frequency, drinking quantity, binge drinking, alcoholism, drinking within 3 hours of suicide attempt, and age began drinking. In bivariate analyses, all measures were associated with nearly lethal suicide…

  11. Survival Study of Zebrafish Embryos Under Gamma Irradiation

    NASA Astrophysics Data System (ADS)

    Mena, Pamela; Allende, Miguel; Morales, José Roberto

    2010-08-01

    Zebrafish embryos have interesting biological properties for the study of human diseases. The present work uses zebrafish embryos in a particular development state, to study biological effects due to gamma radiation, arising from a calibrated 60Co source. Initially, the lethal dose for fish embryos was determined and subsequent irradiations were performed at sub-lethal doses, in order to study more subtle effects.

  12. Deficient repair of potentially lethal damage in actively growing ataxia telangiectasia cells

    SciTech Connect

    Utsumi, H.; Sasaki, M.S.

    1984-02-01

    The repair of potentially lethal damage after X rays was studied in exponentially growing normal and ataxia telangiectasia (A-T) strains of human fibroblasts. X-ray killing of all normal strains from six healthy persons was enhanced when cells were treated with hypertonic phosphate-buffered saline immediately after irradiation. This treatment is not toxic to unirradiated cells and demonstrates that ordinarily these cells repair potentially lethal damage. The potentially lethal damage in normal cells is repaired within 1 hr. In contrast, all A-T strains from four A-T patients were completely deficient in their ability to repair potentially lethal damage. Treatment with a hypertonic solution after X irradiation is known to increase the frequency of chromosomal aberrations and to enhance cell killing, as though hypertonicity had induced the A-T state in normal cells. These results support the inference that the increased radiosensitivity of A-T cells can be attributed to some defect in the repair of DNA damage rather than abnormal DNA synthesis following irradiation.

  13. Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

    PubMed

    Lata, M; Prasad, J; Singh, S; Kumar, R; Singh, L; Chaudhary, P; Arora, R; Chawla, R; Tyagi, S; Soni, N L; Sagar, R K; Devi, M; Sharma, R K; Puri, S C; Tripathi, R P

    2009-01-01

    The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

  14. Lethal outcome in xanthogranulomatous endometritis.

    PubMed

    Noack, Frank; Briese, Juliane; Stellmacher, Florian; Hornung, Daniela; Horny, Hans-Peter

    2006-05-01

    Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists. PMID:16725016

  15. Lethal photosensitization of Helicobacter species

    NASA Astrophysics Data System (ADS)

    Millson, Charles E.; Wilson, Michael; MacRobert, Alexander J.; Thurrell, Wendy; Mlkvy, Peter; Davies, Claire; Bown, Stephen G.

    1995-01-01

    Helicobacter pylori (H. pylori) is associated with a large number of gastroduodenal disorders. Clearance of the bacteria has been shown to benefit patients with duodenal ulcers, gastric ulcers, and certain rare types of gastric tumors. Broad-spectrum antibiotics are the mainstay of current treatment strategies but side-effects, poor compliance, and drug resistance limit their usefulness. We sensitized H. pylori with toluidine blue, haematoporphyrin derivative, aluminum disulphonated phthalocyanine, methylene blue or protoporphyrin IX prior to exposure to low-power laser light from either a gallium aluminum arsenide laser or a helium neon gas laser. All 5 sensitizers caused reductions of greater than 1000-fold in the number of viable bacteria. Light alone had no effect and only HpD caused a significant decrease in bacterial numbers without laser light. Next, we sensitized H. mustelae on explanted ferret gastric mucosa (ex vivo) with the same sensitizers and exposed them to light from a copper vapor pumped dye laser tuned appropriately. MB caused significant reductions in bacterial counts. Successful lethal photosensitization of Helicobacter pylori both in vitro and ex vivo raises the possibility of a local method for eradicating the bacteria, especially as the bacteria are only found in those parts of the upper gastrointestinal tract that are accessible to the endoscope.

  16. Potentiation by caffeine of potentially lethal fast-neutron damage in cultured human cells

    SciTech Connect

    Schroy, C.B.; Furcinitti, P.S.; Todd, P.; Kukulinsky, N.E.

    1980-11-01

    Caffeine was found to potentiate single-dose fast-neutron-induced killing of human T-1 cells when present at 2 mM for 60 hr or more after (and 10 hr before) irradiation. Analyses of survival curves of cells treated with neutrons or X rays with and without caffeine indicate that only the linear, low-dose portion of survival curves is modified. Potentiation of lethality by caffeine is attributed mainly to its effects on single-hit potentially lethal lesions, possibly certain DNA double-strand breaks.

  17. Can Vet Schools Teach without Killing Animals?

    ERIC Educational Resources Information Center

    Mangan, Katherine S.

    2000-01-01

    Discusses a protest by students at the University of Illinois (Urbana) College of Veterinary Medicine over the killing of animals that led to temporary curtailing of lethal animal experiments. Examines the conflict between animal rights groups and some faculty who are openly skeptical about the effectiveness of alternatives to the hands-on…

  18. Intravenous Laser Blood Irradiation, Interstitial Laser Acupuncture, and Electroacupuncture in an Animal Experimental Setting: Preliminary Results from Heart Rate Variability and Electrocorticographic Recordings

    PubMed Central

    He, Wei; Wang, Xiaoyu; Jing, Xianghong; Shi, Hong; Shang, Hongyan; Zhu, Bing

    2013-01-01

    This is the first study to investigate intravenous (i.v.) laser blood irradiation, interstitial (i.st.) laser acupuncture, and electroacupuncture (EA) in combination with heart rate variability (HRV) and electrocorticogram. We investigated 10 male anesthetized Sprague-Dawley rats under the three conditions mentioned previously in Beijing, China, and data analysis was performed in Graz, Europe. For i.v. laser stimulation in the femoral vein and i.st. laser acupuncture at Neiguan (PC6), we used a European system (Modulas needle, Schwa-Medico, Germany; 658 nm, 50 mW, continuous wave mode), and for EA at Neiguan, a Chinese system (Hanshi-100A; Nanjing Jisheng Medical Technology Company, China; 15 Hz, 1 mA). HR, HRV, and electrocorticogram were recorded using a biophysical amplifier AVB-10 (Nihon-Kohden, Japan). HR changed significantly during i.st. laser acupuncture stimulation of Neiguan in anesthetized rats. Total HRV increased insignificantly during i.v. and i.st. laser stimulation. The LF/HF ratio showed significant changes only during i.v. laser blood irradiation. Integrated cortical EEG (electrocorticogram) decreased insignificantly during EA and i.v. laser blood irradiation. Further studies concerning dosage-dependent alterations are in progress. PMID:23476681

  19. [Synthetic lethal genes to mutant p53].

    PubMed

    Tongyang, Liu; Haiqiang, Guo; Meiyan, Zhu; Yingze, Huang; Shuting, Jia; Ying, Luo; Jihong, Zhang

    2015-04-01

    Targeted therapy has become a powerful approach for cancer treatment. Better understanding of oncogenes as well as synthetic lethal interactions with oncogenes will lead to new strategies for tumor-specific treatment. It is well known that mutant p53 plays an important role in tumorigenesis and tumor development. Thus, understanding the synthetic lethal relationship between p53 mutations and interacting genes in tumor is critical for the personalized treatments of p53 mutant tumors. Synthetic lethal genes to mutant p53 can be divided into cell cycle regulators and non-cell cycle regulators. This paper review show these two types of target genes contribute to synthetic lethal interactions with p53 mutations and potential applications of these interactions in anticancer therapy.

  20. On lethal injections and the death penalty.

    PubMed

    1982-10-01

    A brief account is given of the recent adoption by several states of capital punishment by lethal injection and the objections that this move has aroused. Critics argue that, because of difficulties in administering the drugs and in determining the proper dosage, this method may actually be less humane than other means of execution. Articles in medical journals have forcefully expressed the profession's opposition to lethal injections and to physician involvement in their administration.

  1. Combination of opium smoking and hypercholesterolemia augments susceptibility for lethal cardiac arrhythmia and atherogenesis in rabbit.

    PubMed

    Najafipour, Hamid; Joukar, Siyavash

    2012-09-01

    Opium consumption is increasing in some eastern societies, where it is grown. We investigated the effect of opium smoking on plasma atherogenic index and incidence of lethal cardiac arrhythmia, i.e. ventricular tachycardia (VT) and ventricular fibrillation (VF) in rabbits. Animals were divided into two-, normo- and hyper-cholesterolemic main groups fed with normal or high cholesterol diet prior and during short-term and long-term exposure to opium smoke. Then, isoproterenol (3mg/kg, i.p.) was injected to induce cardiac ischemia and animals were followed for 3h for counting of lethal arrhythmia incidence. Long-term opium smoking significantly increased the plasma atherogenic index. In ischemic hearts, opium smoking along with hypercholesterolemia significantly enhanced the incidence of fatal arrhythmia. This vulnerability was not mediated by changes in QT interval. These data suggest that opium smoking, especially in hypercholesterolemic conditions, can be a predisposing factor for atherogenesis and lethal arrhythmia.

  2. Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs

    PubMed Central

    Turner, Wendy C.; Kausrud, Kyrre L.; Beyer, Wolfgang; Easterday, W. Ryan; Barandongo, Zoë R.; Blaschke, Elisabeth; Cloete, Claudine C.; Lazak, Judith; Van Ert, Matthew N.; Ganz, Holly H.; Turnbull, Peter C. B.; Stenseth, Nils Chr.; Getz, Wayne M.

    2016-01-01

    To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1–2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID:27265371

  3. Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs.

    PubMed

    Turner, Wendy C; Kausrud, Kyrre L; Beyer, Wolfgang; Easterday, W Ryan; Barandongo, Zoë R; Blaschke, Elisabeth; Cloete, Claudine C; Lazak, Judith; Van Ert, Matthew N; Ganz, Holly H; Turnbull, Peter C B; Stenseth, Nils Chr; Getz, Wayne M

    2016-01-01

    To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1-2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID:27265371

  4. The hologenomic basis of speciation: gut bacteria cause hybrid lethality in the genus Nasonia.

    PubMed

    Brucker, Robert M; Bordenstein, Seth R

    2013-08-01

    Although the gut microbiome influences numerous aspects of organismal fitness, its role in animal evolution and the origin of new species is largely unknown. Here we present evidence that beneficial bacterial communities in the guts of closely related species of the genus Nasonia form species-specific phylosymbiotic assemblages that cause lethality in interspecific hybrids. Bacterial constituents and abundance are irregular in hybrids relative to parental controls, and antibiotic curing of the gut bacteria significantly rescues hybrid survival. Moreover, feeding bacteria to germ-free hybrids reinstates lethality and recapitulates the expression of innate immune genes observed in conventionally reared hybrids. We conclude that in this animal complex, the gut microbiome and host genome represent a coadapted "hologenome" that breaks down during hybridization, promoting hybrid lethality and assisting speciation.

  5. Theory of lethal mutagenesis for viruses.

    PubMed

    Bull, J J; Sanjuán, R; Wilke, C O

    2007-03-01

    Mutation is the basis of adaptation. Yet, most mutations are detrimental, and elevating mutation rates will impair a population's fitness in the short term. The latter realization has led to the concept of lethal mutagenesis for curing viral infections, and work with drugs such as ribavirin has supported this perspective. As yet, there is no formal theory of lethal mutagenesis, although reference is commonly made to Eigen's error catastrophe theory. Here, we propose a theory of lethal mutagenesis. With an obvious parallel to the epidemiological threshold for eradication of a disease, a sufficient condition for lethal mutagenesis is that each viral genotype produces, on average, less than one progeny virus that goes on to infect a new cell. The extinction threshold involves an evolutionary component based on the mutation rate, but it also includes an ecological component, so the threshold cannot be calculated from the mutation rate alone. The genetic evolution of a large population undergoing mutagenesis is independent of whether the population is declining or stable, so there is no runaway accumulation of mutations or genetic signature for lethal mutagenesis that distinguishes it from a level of mutagenesis under which the population is maintained. To detect lethal mutagenesis, accurate measurements of the genome-wide mutation rate and the number of progeny per infected cell that go on to infect new cells are needed. We discuss three methods for estimating the former. Estimating the latter is more challenging, but broad limits to this estimate may be feasible.

  6. Engineered female-specific lethality for control of pest Lepidoptera.

    PubMed

    Jin, Li; Walker, Adam S; Fu, Guoliang; Harvey-Samuel, Timothy; Dafa'alla, Tarig; Miles, Andrea; Marubbi, Thea; Granville, Deborah; Humphrey-Jones, Nerys; O'Connell, Sinead; Morrison, Neil I; Alphey, Luke

    2013-03-15

    The sterile insect technique (SIT) is a pest control strategy involving the mass release of radiation-sterilized insects, which reduce the target population through nonviable matings. In Lepidoptera, SIT could be more broadly applicable if the deleterious effects of sterilization by irradiation could be avoided. Moreover, male-only release can improve the efficacy of SIT. Adequate methods of male-only production in Lepidoptera are currently lacking, in contrast to some Diptera. We describe a synthetic genetic system that allows male-only moth production for SIT and also replaces radiation sterilization with inherited female-specific lethality. We sequenced and characterized the doublesex (dsx) gene from the pink bollworm (Pectinophora gossypiella). Sex-alternate splicing from dsx was used to develop a conditional lethal genetic sexing system in two pest moths: the diamondback moth (Plutella xylostella) and pink bollworm. This system shows promise for enhancing existing pink bollworm SIT, as well as broadening SIT-type control to diamondback moth and other Lepidoptera.

  7. An outbreak of lethal adenovirus infection among different otariid species.

    PubMed

    Inoshima, Yasuo; Murakami, Tomoaki; Ishiguro, Naotaka; Hasegawa, Kazuhiro; Kasamatsu, Masahiko

    2013-08-30

    An outbreak of fatal fulminant hepatitis at a Japanese aquarium involved 3 otariids: a California sea lion (Zalophus californianus), a South African fur seal (Arctocephalus pusillus) and a South American sea lion (Otaria flavescens). In a span of about a week in February 2012, 3 otariids showed diarrhea and were acutely low-spirited; subsequently, all three animals died within a period of 3 days. Markedly increased aspartate amino transferase and alanine amino transferase activities were observed. Necrotic hepatitis and eosinophilic intranuclear inclusion bodies in liver hepatocytes and intestinal epithelial cells were observed in the South American sea lion on histological examination. Otarine adenovirus DNA was detected from the livers of all three animals by polymerase chain reaction and determination of the sequences showed that all were identical. These results suggest that a single otarine adenovirus strain may have been the etiological agent of this outbreak of fatal fulminant hepatitis among the different otariid species, and it may be a lethal threat to wild and captive otariids. This is the first evidence of an outbreak of lethal adenovirus infection among different otariid species. PMID:23643878

  8. Improving on army field gauze for lethal vascular injuries: a progress report

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Uncontrolled hemorrhage is the leading cause of death on the battlefield and second leading cause of death in civilian trauma. Recent animal testing using a lethal arterial injury model compared a variety of woven and non woven products with granular products, and found only one product (WoundStat)...

  9. Conditional embryonic lethality to improve the sterile insect technique in Ceratitis capitata (Diptera: Tephritidae)

    PubMed Central

    Schetelig, Marc F; Caceres, Carlos; Zacharopoulou, Antigone; Franz, Gerald; Wimmer, Ernst A

    2009-01-01

    Background The sterile insect technique (SIT) is an environment-friendly method used in area-wide pest management of the Mediterranean fruit fly Ceratitis capitata (Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate reproductive sterility in the mass-reared populations before release leads to reduction of competitiveness. Results Here, we present a first alternative reproductive sterility system for medfly based on transgenic embryonic lethality. This system is dependent on newly isolated medfly promoter/enhancer elements of cellularization-specifically-expressed genes. These elements act differently in expression strength and their ability to drive lethal effector gene activation. Moreover, position effects strongly influence the efficiency of the system. Out of 60 combinations of driver and effector construct integrations, several lines resulted in larval and pupal lethality with one line showing complete embryonic lethality. This line was highly competitive to wildtype medfly in laboratory and field cage tests. Conclusion The high competitiveness of the transgenic lines and the achieved 100% embryonic lethality causing reproductive sterility without the need of irradiation can improve the efficacy of operational medfly SIT programs. PMID:19173707

  10. Development of ELISA based detection system for lethal toxin of Clostridium sordellii

    PubMed Central

    Arya, Preetika; Ponmariappan, S.; Singh, Lokendra; Kumar, Om

    2013-01-01

    Background & objectives: Clostridium sordellii and its toxins are associated with diseases in animals as well as human. C. sordellii produces two protein toxins (lethal toxin and haemorrhagic toxin). Lethal toxin has gained more importance due its high toxicity. The present study was carried out to develop a sandwich ELISA for detection of lethal toxin of C. sordellii. Methods: The catalytic domain (1.6kb) of lethal toxin of C. sordellii was PCR amplified, cloned into pQE30 UA vector and transformed into Escherichia coli SG 13009. Expression conditions were optimized and the recombinant protein was purified under native condition using Ni-NTA affinity chromatography, confirmed by SDS-PAGE and Western blot. Antibody was generated against the purified recombinant protein using Freund's complete and incomplete adjuvants (FCA and FIA) in BALB/c mice and rabbit. A sandwich ELISA was optimized for the detection of lethal toxin. Results: The maximum recombinant protein expression was achieved at 0.5 mM IPTG (isopropylthiogalactoside) induction 4.0 h of post-induction. The polyclonal antibody raised in mice and rabbit showed a titre up to 1:512000. The produced antibody was highly sensitive with the detection limit of 0.3 ng/ml of lethal toxin at 1:4000 dilutions of mice (capturing) and rabbit (revealing) antibody. Interpretation & conclusions: An ELISA based detection system was developed for the detection of lethal toxin of C. sordellii. The developed detection system was found to be specific as there was no cross-reactivity with any other clostridial toxins. It will be useful for the detection of lethal toxin of C. sordellii in clinical and environmental samples. PMID:23852299

  11. Carbon monoxide and lethal arrhythmias

    SciTech Connect

    Farber, J.P.; Schwartz, P.J.; Vanoli, E.; Stramba-Badiale, M.; De Ferrari, G.M. )

    1990-12-01

    The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in a previously described chronically maintained animal model of sudden cardiac death. In 60 percent of dogs with a healed anterior myocardial infarction, the combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation. The events in this model are highly reproducible, thus allowing study by internal control analysis. Dogs that develop ventricular fibrillation during the test of exercise and acute myocardial ischemia are considered at high risk for sudden death and are defined as 'susceptible'; dogs that survive the test without a fatal arrhythmia are considered at low risk for sudden death and are defined as 'resistant.' In the current study, the effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates was observed at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. This trend was observed at rest and during exercise in both resistant and susceptible dogs. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, this reflex response occurred earlier and was augmented after exposure to carbon monoxide. This effect may depend on the increased hypoxic challenge caused by carbon monoxide, and thus on an augmentation of the neural reflex activation or a sensitization of the sinus node to acetylcholine induced by hypoxia. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. This worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. (Abstract Truncated)

  12. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... documentation that the establishment is required to maintain under 9 CFR 417.5. (7) The establishment must make... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Control of Listeria monocytogenes in... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a)...

  13. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... documentation that the establishment is required to maintain under 9 CFR 417.5. (7) The establishment must make... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Control of Listeria monocytogenes in... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a)...

  14. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... documentation that the establishment is required to maintain under 9 CFR 417.5. (7) The establishment must make... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Control of Listeria monocytogenes in... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a)...

  15. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... documentation that the establishment is required to maintain under 9 CFR 417.5. (7) The establishment must make... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Control of Listeria monocytogenes in... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a)...

  16. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... documentation that the establishment is required to maintain under 9 CFR 417.5. (7) The establishment must make... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Control of Listeria monocytogenes in... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a)...

  17. Total lymphoid irradiation

    SciTech Connect

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  18. New form of platyspondylic lethal chondrodysplasia.

    PubMed

    Akaba, K; Nishimura, G; Hashimoto, M; Wakabayashi, T; Kanasugi, H; Hayasaka, K

    1996-12-30

    We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The cardinal clinical manifestations consisted of frontal bossing, cloudy corneae, low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia. Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of facial bones and short skull base, extremely severe platyspondyly, hypoplastic ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular bones. The long bones appeared overtubulated with exaggerated metaphyseal flaring. The humeri were particularly short and bowed. Bowing of the radii and ulnae with subluxation of radial heads presented as a Madelung-like deformity. Unlike the long bones, the short tubular bones were not short and normally modeled. The skeletal changes were superficially similar to those in a group of lethal platyspondylic chondrodysplasias, but were inconsistent with any known subtypes of this group or other lethal skeletal dysplasias. PMID:8989469

  19. Inadequate anaesthesia in lethal injection for execution.

    PubMed

    Koniaris, Leonidas G; Zimmers, Teresa A; Lubarsky, David A; Sheldon, Jonathan P

    Anaesthesia during lethal injection is essential to minimise suffering and to maintain public acceptance of the practice. Lethal injection is usually done by sequential administration of thiopental, pancuronium, and potassium chloride. Protocol information from Texas and Virginia showed that executioners had no anaesthesia training, drugs were administered remotely with no monitoring for anaesthesia, data were not recorded and no peer-review was done. Toxicology reports from Arizona, Georgia, North Carolina, and South Carolina showed that post-mortem concentrations of thiopental in the blood were lower than that required for surgery in 43 of 49 executed inmates (88%); 21 (43%) inmates had concentrations consistent with awareness. Methods of lethal injection anaesthesia are flawed and some inmates might experience awareness and suffering during execution.

  20. Relative toxicity testing of spacecraft materials. 1: Spacecraft materials. [lethality of pyrolysates

    NASA Technical Reports Server (NTRS)

    Lawrence, W. H.

    1980-01-01

    In chamber thermodegradation procedures were used to access the lethality to rats of the pyrolysis/combustion products of three foams, an adhesive backed metallic tape and RTV silicone rubber adhesive sealant used in spacecraft construction. The role of carbon monoxide in the overall pyrolysate toxicity was also investigated. Post exposure observation of the rats, histological evaluation of selected organs, carbon monoxide concentration in the chamber atmosphere during exposure and the percent carboxyhemoglobin in the animals expiring in the chamber are discussed. Thermogravimetric analysis and dosage response results are given. The lethal effect of the RTV silicon appears to be due to physical obstruction of the respiratory system by particulate matter from pyrolysis.

  1. Induction of gelatinase B and MCP-2 in baboons during sublethal and lethal bacteraemia.

    PubMed

    Paemen, L; Jansen, P M; Proost, P; Van Damme, J; Opdenakker, G; Hack, E; Taylor, F B

    1997-06-01

    Intravenous injection of sublethal or lethal doses of Escherichia coli in baboons resulted in increased serum levels of the matrix metalloprotease gelatinase B and the chemokine monocyte chemotactic protein 2 (MCP-2). In both animal models, gelatinase B appeared faster than MCP-2. After sublethal challenge, serum levels of gelatinase B and MCP-2 were found to be correlated, reaching peak levels between 2 and 4 h after bacterial challenge. After lethal challenge, however, MCP-2 tended to increase until 10 h. The kinetics of appearance suggest induction of release of gelatinase B and de novo synthesis and secretion of MCP-2, both by endotoxin.

  2. Live deaths online: internet suicide and lethality.

    PubMed

    Klein, Carolina A

    2012-01-01

    The Internet provides an infinite platform for the portrayal of lethal events. Beyond mere display, however, it dispenses information, allows for participation and sharing of content, and constitutes a virtual interactive forum. The Internet may ultimately shape society's approach to perceiving and dealing with death. Thus, psychiatrists may wish to be aware of these matters so that they may be considered in assessments and clinical care. In this article, the author attempts to identify key online locations where lethality is portrayed and how it may affect the individual patient and practitioner and the population at large.

  3. Therapeutically targeting RNA viruses via lethal mutagenesis.

    PubMed

    Graci, Jason D; Cameron, Craig E

    2008-11-01

    RNA viruses exhibit increased mutation frequencies relative to other organisms. Recent work has attempted to exploit this unique feature by increasing the viral mutation frequency beyond an extinction threshold, an antiviral strategy known as lethal mutagenesis. A number of novel nucleoside analogs have been designed around this premise. Herein, we review the quasispecies nature of RNA viruses and survey the antiviral, biological and biochemical characteristics of mutagenic nucleoside analogs, including clinically-used ribavirin. Biological implications of modulating viral replication fidelity are discussed in the context of translating lethal mutagenesis into a clinically-useful antiviral strategy.

  4. Induction of tolerance to a soluble antigen following irradiation and bone marrow reconstitution.

    PubMed

    Schleimer, R P; Scibienski, R J; Vollger, H F; Benjamini, E

    1982-01-01

    Antigen-specific tolerance was induced in mice by lethal irradiation followed by reconstitution with syngeneic, anti-T-cell-treated bone marrow and injection of the protein antigen lysozyme. Animals tolerized with lysozyme responded normally to a second antigen, sheep red blood cells, and animals treated with the same tolerizing regimen using a different protein antigen, bovine serum albumin, responded normally to lysozyme. Challenge of the tolerant mice with lysozyme covalently coupled to LPS induced an antilysozyme response indicating that if tolerance was expressed on the B-cell level that antigen-specific B-cells were still present. These results eliminate clonal abortion and clonal selection as the mechanism of tolerance generation. The tolerance generated by this procedure is either expressed on the T-cell level or is produced by a state of B-cell clonal anergy which can be overcome by the use of antigen coupled to lipopolysaccharide.

  5. Pathogenesis, Lethality, and Immunizing Effect of Experimental Cutaneous Cryptococcosis

    PubMed Central

    Dykstra, Mark A.; Friedman, Lorraine

    1978-01-01

    Mice were subcutaneously inoculated with small numbers of virulent Cryptococcus neoformans and divided into groups. Numbers of viable yeasts at the site were estimated at weekly intervals for 5 weeks on the basis of cultures of minced tissue excised from sacrificed animals. Organisms multiplied at the site for at least 4 weeks and were still detectable after the 5th week, although in reduced numbers. Agglutinins appeared within a week, but these antibodies were not detectable during the 2nd through the 5th week. Cryptococcal polysaccharide began to appear in the sera at 3 weeks, persisting through the duration of 5 weeks. All animals appeared healthy, but a few sickened after many months and died of systemic cryptococcosis. All of these events were observed in many separate experiments. The immunizing capacity of a cutaneous lesion was tested by challenging some of the above animals with viable C. neoformans after various intervals of time, either subcutaneously at a site distant from that of the vaccination or intravenously. Although we were unable to demonstrate reduced multiplication of yeasts in the brains, lungs, and spleens of intravenously challenged animals, it was possible to show that multiplication was inhibited at the site of subcutaneous challenge. It was noted also that vaccinated animals lived longer after lethal intravenous challenge than did nonvaccinated animals. The latter protection was observed, however, only when challenge followed vaccination by 3 weeks or longer, and it was effective only against a relatively low challenge dose. Mice were protected against a higher dose if they had previously received killed cryptococci, alternating subcutaneous and intraperitoneal inoculations, one of which contained a microbial adjuvant. No protection was observed in animals that were subcutaneously vaccinated with inert materials such as chitin, latex spheres, or even cryptococcal cell walls themselves. PMID:352944

  6. Left ventricular function during lethal and sublethal endotoxemia in swine

    SciTech Connect

    Goldfarb, R.D.; Nightingale, L.M.; Kish, P.; Weber, P.B.; Loegering, D.J.

    1986-08-01

    Previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. The authors retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because of the hepatic circulation in this species is similar to that of humans. They compared cardiac mechanical function of pigs administered a high dose (250 g/kg) or a low dose (100 g/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardia depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. Myocardial perfusion was measured using radiolabeled microspheres infused into the left atria.

  7. Macrophage cytotoxicity in lethal and non-lethal murine malaria and the effect of vaccination.

    PubMed Central

    Taverne, J; Treagust, J D; Playfair, J H

    1986-01-01

    We investigated the development of cell-mediated immunity in lethal and non-lethal malarial infections by assaying the cytotoxic activity of spleen cells for L929 tumour cells at different times after infection of mice with the lethal P. berghei, a lethal variant of Plasmodium yoelii and the non-lethal P. yoelii and P. chabaudi. In all cases the cytotoxicity increased to a peak during the first week and then diminished but the time of the peak varied with the infection; its activity was lowest with P. berghei. A second peak occurred in the non-lethal infections at the time of recovery. A protective vaccine accelerated and enhanced the early peak of cytotoxicity. The activity was mediated by adherent phagocytic cells, probably through the release of tumour necrosis factor (TNF) by macrophages since it was inhibited by antiserum against recombinant mouse TNF and did not destroy TNF-resistant L929 cells. Its induction was not dependent on T cells since it occurred in T cell-deficient mice infected with non-lethal P. yoelii. However, the accelerated increase associated with vaccination could be adoptively transferred by spleen lymphocytes from vaccinated mice. PMID:3542317

  8. Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

    PubMed Central

    Cheresiz, S. V.; Semenova, E. A.; Chepurnov, A. A.

    2016-01-01

    Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

  9. Suicide intent and accurate expectations of lethality: predictors of medical lethality of suicide attempts.

    PubMed

    Brown, Gregory K; Henriques, Gregg R; Sosdjan, Daniella; Beck, Aaron T

    2004-12-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate the relationship between suicide intent and lethality. Specifically, higher levels of suicide intent were associated with more lethal attempts but only for those individuals who had more accurate expectations about the likelihood of dying from their attempts.

  10. Enhancing the stability and ecological safety of mass-reared transgenic strains for field release by redundant conditional lethality systems.

    PubMed

    Handler, Alfred M

    2016-04-01

    The genetic manipulation of agriculturally important insects now allows the development of genetic sexing and male sterility systems for more highly efficient biologically-based population control programs, most notably the Sterile Insect Technique (SIT), for both plant and animal insect pests. Tetracycline-suppressible (Tet-off) conditional lethal systems may function together so that transgenic strains will be viable and fertile on a tetracycline-containing diet, but female-lethal and male sterile in tetracycline-free conditions. This would allow their most efficacious use in a unified system for sterile male-only production for SIT. A critical consideration for the field release of such transgenic insect strains, however, is a determination of the frequency and genetic basis of lethality revertant survival. This will provide knowledge essential to evaluating the genetic stability of the lethality system, its environmental safety, and provide the basis for modifications ensuring optimal efficacy. For Tet-off lethal survival determinations, development of large-scale screening protocols should also allow the testing of these modifications, and test the ability of other conditional lethal systems to fully suppress propagation of rare Tet-off survivors. If a dominant temperature sensitive (DTS) pupal lethality system proves efficient for secondary lethality in Drosophila, it may provide the safeguard needed to support the release of sexing/sterility strains, and potentially, the release of unisex lethality strains as a form of genetic male sterility. Should the DTS Prosβ2(1) mutation prove effective for redundant lethality, its high level of structural and functional conservation should allow host-specific cognates to be created for a wide range of insect species.

  11. Deadly Lessons: Understanding Lethal School Violence.

    ERIC Educational Resources Information Center

    Moore, Mark H., Ed.; Petrie, Carol V., Ed.; Braga, Anthony A., Ed.; McLaughlin, Brenda L., Ed.

    This collection of papers is the outcome of the National Academies' effort to glean information from six different case studies of student-perpetrated school shootings. Part 1, "Case Studies of Lethal School Violence," includes: "The Copycat Factor: Mental Illness, Guns, and the Shooting Incident at Heritage High School, Rockdale County, Georgia"…

  12. The evolution of lethal intergroup violence

    PubMed Central

    Kelly, Raymond C.

    2005-01-01

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry. PMID:16129826

  13. Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium.

    PubMed

    Fernando, Vindhya A K; Weerasena, Jagathpriya; Lakraj, G Pemantha; Perera, Inoka C; Dangalle, Chandima D; Handunnetti, Shiroma; Premawansa, Sunil; Wijesinghe, Mayuri R

    2016-08-01

    Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems. PMID:27262939

  14. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX.

  15. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. PMID:26621540

  16. Protection against both lethal and behavioral effects of soman.

    PubMed

    Harris, L W; McDonough, J H; Stitcher, D L; Lennox, W J

    1984-01-01

    This work developed two drug mixtures which alone had no effect on performance of a criterion behavior but when given as a pretreatment would protect against organophosphate-induced lethality and incapacitation. Candidate drugs (alone and together) were given to rats trained to respond on a two-component Fixed Ratio 10 - Extinction (FR10-EXT) schedule. After generating dose response curves for each cholinolytic drug, mixtures of atropine (A) + mecamylamine (M) + pyridostigmine (Py) or physostigmine (Ph) were prepared and a combination of doses that produced no effects on operant performance was determined (Mix I:A = .78, M = .78, Py = .056 mg/kg; Mix II:A = .78, M = .78, Ph = .026 mg/kg). Both pretreatment mixtures provided equivalent protection against the lethal effects of the organophosphate soman; however only Mix II was capable of reversing soman-induced physical incapacitation (PI) as assessed by performance on an accelerating rotarod or FR10 responding. Pretreatment of animals with Mix II resulted in significantly higher levels of brain acetylcholinesterase (AChE) than Mix I pretreated subjects 4 hrs after 1.3 LD50 soman, although peripheral AChE levels were not different. The results indicate organophosphate-induced PI can be attenuated by pretreatment with tertiary carbamates which protect significant amounts of brain AChE from irreversible inhibition.

  17. "Terminal burrowing behaviour"--a phenomenon of lethal hypothermia.

    PubMed

    Rothschild, M A; Schneider, V

    1995-01-01

    Between 1978 and 1994, 69 cases of death due to lethal hypothermia were examined in our Institute. In addition to the common findings associated with hypothermia we especially wanted to examine the so-called paradox reaction which refers to the undressing of persons in a state of severe (lethal) hypothermia. This is obviously the result of a peripheral vasodilatation effecting a feeling of warmth. In our material this paradoxical undressing occurred in 25% of the cases and nearly all exhibited an additional phenomenon which has not yet been described in the literature. Nearly all bodies with partial or complete disrobement were found in a position which indicated a final mechanism of protection i.e. under a bed, behind a wardrobe, in a shelf etc.. This is obviously an autonomous process of the brain stem, which is triggered in the final state of hypothermia and produces a primitive and burrowing-like behaviour of protection, as seen in (hibernating) animals. This phenomenon, which we refer to as "terminal burrowing behaviour", occurred predominantly with slow decreases in temperature and moderately cold conditions. PMID:7632602

  18. Lethal graft-versus-host disease in nude mice. I. Establishment of model systems

    SciTech Connect

    Kuribayashi, K.; Masuda, T.; Hanaoka, M.

    1988-08-01

    We examined whether nude mice, which are deficient in T cell function, could be used as a model for induction of lethal graft-versus-host disease. Nude mice injected with MHC-disparate spleen cells exhibited only transient GVH reaction such as splenomegaly. Inoculation of B6 spleen cells into BALB/c nude mice produced high titers of alloantibodies to the donor cells. These alloantibodies eliminated host-MHC-reactive donor T cells from the host. After abolition by 400 rads irradiation of the capacity of nude mice to produce antibody, lethal GVHD could be induced by allogeneic spleen cell transfer and was mediated by donor T cells. This lethal GVHD was prevented by prior administration of antidonor alloantibody to the irradiated recipients at least 24 hr before donor-cell grafting. The role of alloantibody was substantiated in 2 other combinations in which little or no alloantibodies to donor spleen cells were produced. Engraftment of either MHC-identical but non-MHC disparate donor spleen cells into BALB/c nude mice or of parental spleen cells into F1 nude mice resulted in death mediated by T cells. In addition, irradiated BALB/c nude mice inoculated with non-MHC-incompatible B10.D2 spleen cells were much more sensitive to alloaggression by the donor cells than were nonirradiated hosts, indicating the presence of some radiation-sensitive component(s) acting in nude mice against GVHD induction by donor T cells. Thus the nude mouse is considered to be a useful recipient for clarifying the basic mechanisms involved in lethal GVHD.

  19. Cholesterol Metabolism and Prostate Cancer Lethality.

    PubMed

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

  20. Pseudomonas aeruginosa UV-A-induced lethal effect: influence of salts, nutritional stress and pyocyanine.

    PubMed

    Fernández, R O; Pizarro, R A

    1999-05-01

    The presence of NaCl in plating media shows an important protection against the Pseudomonas aeruginosa UV-A-induced lethal effect, contrasting with the known sensitizing action of salts on UV-A-irradiated Escherichia coli cells. MgSO4 exhibits a similar protection, but lower concentrations than for NaCl are needed to achieve the same effect. NaCl protection from lethal effects involves an osmotic mechanism, while MgSO4 could act by a different process. On the other hand, when cells grown in a complete medium are then incubated for 20 min in a synthetic medium and irradiated with UV-A, a very marked protection is obtained. This protection is dependent on protein synthesis, since treatment with tetracycline, during the nutritional stress, blocks its induction. These results offer a new example of cross-protection among different stressing agents. In our experimental conditions, natural phenazines of P. aeruginosa are not present in the cells, ruling out the possibility that these pigments act as photosensitizers. Conversely, pyocyanine (the major phenazine produced by this microorganism) prevents the UV-A killing effect in a concentration-dependent way when present in the irradiation media. Finally, UV-A irradiation induces, as in E. coli, the accumulation of guanosine tetraphosphate and guanosine pentaphosphate, although the physiological meaning of this finding has yet to be determined. PMID:10443032

  1. Non-lethal sampling of walleye for stable isotope analysis: a comparison of three tissues

    USGS Publications Warehouse

    Chipps, Steven R.; VanDeHey, J.A.; Fincel, M.J.

    2012-01-01

    Stable isotope analysis of fishes is often performed using muscle or organ tissues that require sacrificing animals. Non-lethal sampling provides an alternative for evaluating isotopic composition for species of concern or individuals of exceptional value. Stable isotope values of white muscle (lethal) were compared with those from fins and scales (non-lethal) in walleye, Sander vitreus (Mitchill), from multiple systems, size classes and across a range of isotopic values. Isotopic variability was also compared among populations to determine the potential of non-lethal tissues for diet-variability analyses. Muscle-derived isotope values were enriched compared with fins and depleted relative to scales. A split-sample validation technique and linear regression found that isotopic composition of walleye fins and scales was significantly related to that in muscle tissue for both δ13C and δ15N (r2 = 0.79–0.93). However, isotopic variability was significantly different between tissue types in two of six populations for δ15N and three of six populations for δ13C. Although species and population specific, these findings indicate that isotopic measures obtained from non-lethal tissues are indicative of those obtained from muscle.

  2. Low dose of continuous – wave microwave irradiation did not cause temperature increase in muscles tissue adjacent to titanium alloy implants – an animal study

    PubMed Central

    2013-01-01

    Background Research studies on the influence of radiofrequency electromagnetic radiation on implants in vitro have failed to investigate temperature changes in the tissues adjacent to the implants under microwave therapy. We therefore, used a rabbit model in an effort to determine the impact of microwave therapy on temperature changes in tissues adjacent to the titanium alloy implants and the safety profile thereof. Methods Titanium alloy internal fixation plates were implanted in New Zealand rabbits in the middle of femur. Microwave therapy was performed by a 2450 MHz microwave generator 3 days after the surgery. Temperature changes of muscles adjacent to the implants were recorded under exposure to dose-gradient microwave radiation from 20w to 60w. Results Significant difference between control and microwave treatment group at peak temperatures (Tpeak) and temperature gap (Tgap= Tpeak-Tvally) were observed in deep muscles (Tpeak, 41.63 ± 0.21°C vs. 44.40 ± 0.17°C, P < 0.01; Tgap, 5.33 ± 0.21°C vs. 8.10 ± 0.36°C, P < 0.01) and superficial muscles (Tpeak, 41.53 ± 0.15°C vs. 42.03 ± 0.23°C, P = 0.04; Tgap, 5.23 ± 0.21°C vs. 5.80 ± 0.17°C, P = 0.013) under 60 w, and deep muscles (Tpeak, 40.93 ± 0.25°C vs. 41.87 ± 0.23°C, P = 0.01; Tgap, 4.73 ± 0.20°C vs. 5.63 ± 0.35°C, P = 0.037) under 50w, but not under 20, 30 and 40w. Conclusion Our results suggest that low-dose (20w-40w) continuous-wave microwave irradiation delivered by a 2450 MHz microwave generator might be a promising treatment for patients with titanium alloy internal fixation, as it did not raise temperature in muscle tissues adjacent to the titanium alloy implant. PMID:24365389

  3. Batrachochytrium dendrobatidis infection and lethal chytridiomycosis in caecilian amphibians (Gymnophiona).

    PubMed

    Gower, David J; Doherty-Bone, Thomas; Loader, Simon P; Wilkinson, Mark; Kouete, Marcel T; Tapley, Benjamin; Orton, Frances; Daniel, Olivia Z; Wynne, Felicity; Flach, Edmund; Müller, Hendrik; Menegon, Michele; Stephen, Ian; Browne, Robert K; Fisher, Mathew C; Cunningham, Andrew A; Garner, Trenton W J

    2013-06-01

    Batrachochytrium dendrobatidis (Bd) is commonly termed the 'amphibian chytrid fungus' but thus far has been documented to be a pathogen of only batrachian amphibians (anurans and caudatans). It is not proven to infect the limbless, generally poorly known, and mostly soil-dwelling caecilians (Gymnophiona). We conducted the largest qPCR survey of Bd in caecilians to date, for more than 200 field-swabbed specimens from five countries in Africa and South America, representing nearly 20 species, 12 genera, and 8 families. Positive results were recovered for 58 specimens from Tanzania and Cameroon (4 families, 6 genera, 6+ species). Quantities of Bd were not exceptionally high, with genomic equivalent (GE) values of 0.052-17.339. In addition, we report the first evidence of lethal chytridiomycosis in caecilians. Mortality in captive (wild-caught, commercial pet trade) Geotrypetes seraphini was associated with GE scores similar to those we detected for field-swabbed, wild animals.

  4. Batrachochytrium dendrobatidis infection and lethal chytridiomycosis in caecilian amphibians (Gymnophiona).

    PubMed

    Gower, David J; Doherty-Bone, Thomas; Loader, Simon P; Wilkinson, Mark; Kouete, Marcel T; Tapley, Benjamin; Orton, Frances; Daniel, Olivia Z; Wynne, Felicity; Flach, Edmund; Müller, Hendrik; Menegon, Michele; Stephen, Ian; Browne, Robert K; Fisher, Mathew C; Cunningham, Andrew A; Garner, Trenton W J

    2013-06-01

    Batrachochytrium dendrobatidis (Bd) is commonly termed the 'amphibian chytrid fungus' but thus far has been documented to be a pathogen of only batrachian amphibians (anurans and caudatans). It is not proven to infect the limbless, generally poorly known, and mostly soil-dwelling caecilians (Gymnophiona). We conducted the largest qPCR survey of Bd in caecilians to date, for more than 200 field-swabbed specimens from five countries in Africa and South America, representing nearly 20 species, 12 genera, and 8 families. Positive results were recovered for 58 specimens from Tanzania and Cameroon (4 families, 6 genera, 6+ species). Quantities of Bd were not exceptionally high, with genomic equivalent (GE) values of 0.052-17.339. In addition, we report the first evidence of lethal chytridiomycosis in caecilians. Mortality in captive (wild-caught, commercial pet trade) Geotrypetes seraphini was associated with GE scores similar to those we detected for field-swabbed, wild animals. PMID:23677560

  5. Prevalence of lethal osteochondrodysplasias in Denmark.

    PubMed

    Andersen, P E

    1989-04-01

    The point prevalence at birth of lethal osteochondrodysplasias in a subregion of Denmark was estimated by a study of all children born January 1970 through December 1983. Two cases of thanatophoric dysplasia, one case of thanatophoric dysplasia with cloverleaf skull, two cases of micromelic bone dysplasia with cloverleaf skull, two cases of achondrogenesis type III, and three cases of achondrogenesis type IV were found. Two cases were unclassifiable due to lack of radiographs. In total, the point prevalence at birth was 15.4 per 100,000. Thus lethal osteochondrodysplasias seem to be more common than is generally assumed. The clinical and radiographic findings in micromelic bone dysplasia with cloverleaf skull are discussed in relation to thanatophoric dysplasia and achondrogenesis type IV. PMID:2789000

  6. Brine shrimp lethality assay of Bacopa monnieri.

    PubMed

    D'Souza, Prashanth; Deepak, Mundkinajeddu; Rani, Padmaja; Kadamboor, Sandhya; Mathew, Anjana; Chandrashekar, Arun P; Agarwal, Amit

    2002-03-01

    Successive petroleum ether, chloroform, ethanol and water extracts, a saponin rich fraction (SRF) and bacoside A isolated from Bacopa monnieri were tested for brine shrimp lethality. Successive ethanol extracts and SRF showed potent activity. Bacoside A showed the maximum activity with a LC(50) of 38.3 microg/mL. The results confirmed the previous reports of an anticancer effect of Bacopa monnieri and suggest bacoside A as the active constituent. PMID:11933129

  7. Brine shrimp lethality assay of Bacopa monnieri.

    PubMed

    D'Souza, Prashanth; Deepak, Mundkinajeddu; Rani, Padmaja; Kadamboor, Sandhya; Mathew, Anjana; Chandrashekar, Arun P; Agarwal, Amit

    2002-03-01

    Successive petroleum ether, chloroform, ethanol and water extracts, a saponin rich fraction (SRF) and bacoside A isolated from Bacopa monnieri were tested for brine shrimp lethality. Successive ethanol extracts and SRF showed potent activity. Bacoside A showed the maximum activity with a LC(50) of 38.3 microg/mL. The results confirmed the previous reports of an anticancer effect of Bacopa monnieri and suggest bacoside A as the active constituent.

  8. Specific ultrasonographic features of perinatal lethal hypophosphatasia.

    PubMed

    Zankl, Andreas; Mornet, Etienne; Wong, Shell

    2008-05-01

    Prenatal diagnosis of perinatal lethal hypophosphatasia (PL-HPH) by ultrasonography is difficult as PL-HPH must be differentiated from other skeletal dysplasias with short long bones and poor mineralization of the skeleton, such as osteogenesis imperfecta type II and achondrogenesis/hypochondrogenesis. Here we present a case of molecularly confirmed PL-HPH and illustrate specific ultrasonographic findings that help to distinguish PL-HPH from similar conditions. PMID:18386808

  9. Lethal interpersonal violence in the Middle Pleistocene.

    PubMed

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin. PMID:26018668

  10. Lethal Interpersonal Violence in the Middle Pleistocene

    PubMed Central

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M.; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin. PMID:26018668

  11. Lethal interpersonal violence in the Middle Pleistocene.

    PubMed

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  12. Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

    SciTech Connect

    Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

    1983-01-01

    Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice.

  13. Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I.

    PubMed

    Grompe, M; Lindstedt, S; al-Dhalimy, M; Kennaway, N G; Papaconstantinou, J; Torres-Ramos, C A; Ou, C N; Finegold, M

    1995-08-01

    Hereditary tyrosinaemia type I, a severe autosomal recessive metabolic disease, affects the liver and kidneys and is caused by deficiency of fumarylacetoacetate hydrolase (FAH). Mice homozygous for a FAH gene disruption have a neonatal lethal phenotype caused by liver dysfunction and do not represent an adequate model of the human disease. Here we demonstrate that treatment of affected animals with 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3-cyclohexanedione abolished neonatal lethality, corrected liver function and partially normalized the altered expression pattern of hepatic mRNAs. The prolonged lifespan of affected animals resulted in a phenotype analogous to human tyrosinaemia type I including hepatocellular carcinoma. The adult FAH-/- mouse will serve as useful model for studies of the pathophysiology and treatment of hereditary tyrosinaemia type I as well as hepatic cancer. PMID:7545495

  14. Optimization irradiation conditions for determination of LD50 in pigs.

    PubMed

    Procházka, Z; Hampl, J; Sedlácek, M; Rodák, L

    1975-11-01

    Radiation LD50/30 values were determined in 36 twelve-week-old pigs (with a mean body weigth of 21 kg) exposed to whole-body X-ray irradiation on a revolvable table rotated at a rate of 2.5 rpm using the following conditions: 180 kV, 15 mA, focal distance 79 cm, HVT 0.9 mm Cu, dose rate 2.42 X 10(-3) to 2.68 X 10(-3) C kg-1 min-1 (9.4 to 10.4 R/min) depending upon the animal size. The coefficient of mean irradiation uniformity was 1.4. Under these conditions the LD50/30 for pigs was found to be 5.89 X 10(-2) C kg-1 min-1 (228.3 R) with the biological range of effectiveness being 5.22 X 10(-2) to 6.90 X 10-(2) C kg-1 (202.4 to 267.6 R). Furthermore experiments on 77 pigs showed that LD50 determined in this study had actually the median lethal effect.

  15. Reliability of non-lethal surveillance methods for detecting ranavirus infection.

    PubMed

    Gray, Matthew J; Miller, Debra L; Hoverman, Jason T

    2012-05-15

    Ranaviruses have been identified as the etiologic agent in many amphibian die-offs across the globe. Polymerase chain reaction (PCR) is commonly used to detect ranavirus infection in amphibian hosts, but the test results may vary between tissue samples obtained by lethal and non-lethal procedures. Testing liver samples for infection is a common lethal sampling technique to estimate ranavirus prevalence because the pathogen often targets this organ and the liver is easy to identify and collect. However, tail clips or swabs may be more practicable for ranavirus surveillance programs compared with collecting and euthanizing animals, especially for uncommon species. Using PCR results from liver samples for comparison, we defined false-positive test results as occurrences when a non-lethal technique indicated positive but the liver sample was negative. Similarly, we defined false-negative test results as occurrences when a non-lethal technique was negative but the liver sample was positive. Using these decision rules, we estimated false-negative and false-positive rates for tail clips and swabs. Our study was conducted in a controlled facility using American bullfrog Lithobates catesbeianus tadpoles; false-positive and false-negative rates were estimated after different periods of time following exposure to ranavirus. False-negative and false-positive rates were 20 and 6%, respectively, for tail samples, and 22 and 12%, respectively, for swabs. False-negative rates were constant over time, but false-positive rates decreased with post-exposure duration. Our results suggest that non-lethal sampling techniques can be useful for ranavirus surveillance, although the prevalence of infection may be underestimated when compared to results obtained with liver samples. PMID:22585297

  16. Reliability of non-lethal surveillance methods for detecting ranavirus infection.

    PubMed

    Gray, Matthew J; Miller, Debra L; Hoverman, Jason T

    2012-05-15

    Ranaviruses have been identified as the etiologic agent in many amphibian die-offs across the globe. Polymerase chain reaction (PCR) is commonly used to detect ranavirus infection in amphibian hosts, but the test results may vary between tissue samples obtained by lethal and non-lethal procedures. Testing liver samples for infection is a common lethal sampling technique to estimate ranavirus prevalence because the pathogen often targets this organ and the liver is easy to identify and collect. However, tail clips or swabs may be more practicable for ranavirus surveillance programs compared with collecting and euthanizing animals, especially for uncommon species. Using PCR results from liver samples for comparison, we defined false-positive test results as occurrences when a non-lethal technique indicated positive but the liver sample was negative. Similarly, we defined false-negative test results as occurrences when a non-lethal technique was negative but the liver sample was positive. Using these decision rules, we estimated false-negative and false-positive rates for tail clips and swabs. Our study was conducted in a controlled facility using American bullfrog Lithobates catesbeianus tadpoles; false-positive and false-negative rates were estimated after different periods of time following exposure to ranavirus. False-negative and false-positive rates were 20 and 6%, respectively, for tail samples, and 22 and 12%, respectively, for swabs. False-negative rates were constant over time, but false-positive rates decreased with post-exposure duration. Our results suggest that non-lethal sampling techniques can be useful for ranavirus surveillance, although the prevalence of infection may be underestimated when compared to results obtained with liver samples.

  17. Fixation of potentially lethal radiation damage in Chinese hamster cells by anisotonic solutions, polyamines, and DMSO

    SciTech Connect

    Raaphorst, G.P.; Azzam, E.I.

    1981-04-01

    The effect of anisotonic solutions, dimethyl sulfoxide (DMSO), and polyamines on the fixation of potentially lethal damage (PLD) was examined. Exposure to anisotonic solutions after irradiation resulted in large decreases in cell survival in a radiation dose-dependent manner. Maximum increase in survival due to repair of PLD in V79 cells after a 1000-rad dose was about a factor of 4 while maximum decrease in survival due to fixation of damage was greater than 1000 times for some of the salt treatments tested. Irradiation at 0/sup 0/C resulted in more damage fixation by 0.05 or 1.5 M NaCl than irradiation at 37/sup 0/C. Fixation of PLD was also observed when cells were exposed to 1.0 or 1.0 M DMSO or 0.1 mM spermine or spermidine solutions. Fixation occurred in both exponentially growing cells and plateau-phase cells. The data demonstrate that a large amount of PLD which is normally not expressed can be converted to lethal damage by a variety of postirradiation treatments and that the PLD repair capacity of the cell may be very large.

  18. Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus.

    PubMed

    Iannacone, Matteo; Sitia, Giovanni; Isogawa, Masanori; Whitmire, Jason K; Marchese, Patrizia; Chisari, Francis V; Ruggeri, Zaverio M; Guidotti, Luca G

    2008-01-15

    We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted of platelets or lacking integrin beta3. Lethal hemorrhagic anemia is mediated by virus-induced IFN-alpha/beta that causes platelet dysfunction, mucocutaneous blood loss and suppression of erythropoiesis. In addition to the life-threatening hemorrhagic anemia, platelet-depleted mice fail to mount an efficient cytotoxic T lymphocyte (CTL) response and cannot clear LCMV. Transfusion of functional platelets into these animals reduces hemorrhage, prevents death and restores CTL-induced viral clearance in a manner partially dependent on CD40 ligand (CD40L). These results indicate that, upon activation, platelets expressing integrin beta3 and CD40L are required for protecting the host against the induction of an IFN-alpha/beta-dependent lethal hemorrhagic diathesis and for clearing LCMV infection through CTLs.

  19. Antiradiation vaccine: Technology and development of prophylaxis, prevention and treatment of biological consequences from Heavy Ion irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav

    . Results: Group A -100% mortality within two hours after heavy ion irradiation with clinical symptoms of the acute cerebrovascular and cardiovascular syndromes. Group B -100% mortal-ity within 15 hours following irradiation. Group C -100% mortality within 14-15 hours after irradiation. Group D -100% mortality within 15-16 hours after irradiation. In groups A-D, development of the acute radiation cerebrovascular and cardiovascular syndromes as well as ex-tensive burns of skin caused rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation while animals were exhibiting a combination or individual forms of the acute cerebrovascular, cardiovascular, and gastrointestinal forms and focal skin burns. Discussion: The Antiradiation Vaccine (ARV) and specific immune-prophylaxis are an effective method of neutralization of Radiation Toxins. Vaccination with the ARV significantly extended the survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of the Acute Radiation Syndromes were diminished in their severity. Groups A-D demonstrated an extremely severe degree (Degree 4) of Cerebrovascular and Cardiovascular forms of the Acute Radiation Syndromes and lethality 100% was registered in a short time after irradiation. Radi-ation induced burns in this groups (with Cutaneous sub-syndrome of ARS -Degree 4) that were deep with extensive and total dysfunction and possible muscle involvement developed. Animals from group E -Radioprotectant -anti-radiation vaccine had demonstrated later development of the severe Degree 3 or even Degree 2-3 forms of Cerebrovascular and Cardiovascular forms of the ARS and a survival time of irradiated animals was significantly prolonged. Cutaneous sub-syndrome developed in Degree 3 or Degree 2-3. Our results have demonstrated the potential radioprotection efficacy of specific immune-prophylaxis with the

  20. Pesticidal residues in animal tissues

    USGS Publications Warehouse

    DeWitt, J.B.; Menzie, C.M.; Adomaitis, V.A.; Reichel, W.L.

    1960-01-01

    Tests with penned starlings, rats, pheasants, and ducks indicated that each species differs in sensitivity to the various pesticides. Residues in tissues are proportional to the degree of exposure during area treatment and they are also found in animals shot six or more months after treatment. The presence of more than 20-30 ppm of DDT, 20 ppm of chlordan, and 6-20 ppm of heptachlor epoxide in quail tissues indicated that the birds had ingested lethal dosages of the pesticides.

  1. Lethal Dietary Toxicities of Environmental Contaminants and Pesticides to Coturnix

    USGS Publications Warehouse

    Hill, E.F.; Camardese, M.B.

    1986-01-01

    Five-day subacute dietary toxicity tests of 193 potential environmental contaminants, pesticides, organic solvents, and various adjuvants are presented for young coturnix (Japanese quail, Coturnix japonica Temminck and Schlegel). The report provides the most comprehensive data base available for avian subacute dietary toxicity tests and is primarily intended for use in ranking toxicities by a standard method that has a reasonable degree of environmental relevance. Findings are presented in two parts: Part I is a critique of selected drugs that includes discussion of subacute toxicity in relation to chemical class and structure, pesticide formulation, and age of animals; Part II is a summary of toxicologic findings for each test substance and provides a statistically basis for comparing toxicities. Data presented include the median lethal concentration (LC50), slope of the probit regression curve (dose-response curve), response chronology, and food consumption. We observed that: 1) fewer than 15% of the compounds were classed 'very' or 'highly' toxic (i.e, LC50 < 200 ppm) and all of these were either chlorinated hydrocarbons, organophosphates, or organometallics; 2) subacute toxicity may vary widely among structurally similar chemicals and between different formulations of the same chemical; therefore, conclusions about lethal hazard must be made cautiously until the actual formulation of inset has been tested: 3) inclusion of a general standard in each battery of tests is useful for detection of atypical trials and monitoring population changes but should not be used indiscriminantly for adjusting LC50's for intertest differences unless the chemicals of concern and the standard elicit their toxicities through the same action; 4) although other species have been tested effectively under the subacute protocol, coturnix were ideal for the stated purpose of this research because they are inexpensive, well-adapted to the laboratory environment, and yield good intertest

  2. Dermal grafts to bony defects in irradiated and nonirradiated tissues

    SciTech Connect

    Lambert, P.M.; Patel, M.; Gutman, E.; Campana, H.A.

    1984-10-01

    Coverage of intraoral ablative defects presents many different problems. Free dermal grafts have been used to cover exposed mandibular bone in dogs. Grafts were placed in animals both before and after irradiation. Grafts were uniformly successful in animals not previously irradiated but failed when placed after irradiation.

  3. [Lethal intoxication with arsenic using prepared butter].

    PubMed

    Weller, Jens-Peter; Larsch, Klaus-Peter; Teske, Jörg; Tröger, Hans Dieter

    2008-01-01

    The present case report deals with a lethal intoxication with arsenic mixed into butter. It describes the course of events over about two days on the basis of the statements by the persons involved, the clinical findings after the belated hospitalisation of the victim, the results of the first pathological autopsy, the forensic autopsy performed after exhumation and the results of the chemical-toxicological investigations. The results are discussed in relation to the later confession of the female perpetrator and her statements regarding a previous unsuccessful murder attempt by poisoning. It also presents the judgement pronounced by the court and the reasons given for it.

  4. Lethal predators: psychopathic, sadistic, and sane.

    PubMed

    Ochberg, Frank M; Brantley, Alan C; Hare, R D; Houk, Peter D; Ianni, Robert; James, Earl; O'Toole, Mary Ellen; Saathoff, Gregory

    2003-01-01

    The violent criminals defined in this article are a small, exceptionally dangerous group of offenders designated by the authors as "lethal predators." They have a history of sexual predation, have killed at least once, and are mentally abnormal but legally sane. They are highly likely to keep killing as long as they are free. Laws permitting civil commitment of dangerous and mentally abnormal sexual predators after they have completed criminal prison sentences have been upheld by the U.S. Supreme Court. Such laws can provide a legal means of keeping these highly dangerous killers confined so they cannot kill again.

  5. Lethal mobilization of DDT by cowbirds

    USGS Publications Warehouse

    Van Velzen, A.C.; Stiles, W.B.; Stickel, L.F.

    1972-01-01

    This study is an experimental demonstration of lethal mobilization of DDT by brown-headed cowbirds (Molothrus ater) and the effects of food deprivation on the distribution and loss of DDT, DDD, and DDE. The principal experimental group consisted of 20 birds fed a dietary dosage of 100 ppm of DDT for 13 days. After 2 days of full rations of untreated food, they were subjected to food restriction. Food was reduced to 43 percent of normal. Seven of the 20 birds died within 4 days. No birds died in the three control groups, treated as follows: ( 1 ) 20 birds fed 100 ppm DDT for 13 days and full rations of untreated food thereafter, (2) 20 birds fed only untreated food but subjected to food restriction, and (3) 20 birds fed full rations of untreated food throughout. In a pilot study, birds were fed 100, 200, or 300 ppm of DDT and subjected to two periods of food restriction, the first of these immediately after dosage ceased and the second 4 months later. DDT-dosed birds from all dosage levels died in each period of food restriction. Before the weight loss that accompanied food restriction, the brains of DDT-dosed birds had concentrations of DDT and DDD that were far below the lethal range. Concentrations increased rapidly to lethal levels. In these birds, DDT in carcasses decreased while DDD increased. DDT-dosed birds that died during food restriction lost 16 percent of their total body burden of DDT + DDD + DDE, 21 percent of their weight, and 81 percent of their fat. The DDT-dosed birds that were subjected to food restriction but survived lost a significantly greater proportion of their body burden of residues than similarly dosed birds not subjected to weight loss. Brain levels of DDT and DDD in birds that died during food restriction soon after dosage did not differ significantly from brain levels of birds that died in a period of food restriction 4 months after dosage. Concentrations of DDE were significantly higher in the latter group, although they were lower

  6. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation

    PubMed Central

    2014-01-01

    Background The hematopoietic syndrome of the acute radiation syndrome (HSARS) is a life-threatening condition in humans exposed to total body irradiation (TBI); no drugs are approved for treating this condition. Recombinant human interleukin-12 (rHuIL-12) is being developed for HSARS mitigation under the FDA Animal Rule, where efficacy is proven in an appropriate animal model and safety is demonstrated in humans. Methods In this blinded study, rhesus monkeys (9 animals/sex/dose group) were randomized to receive a single subcutaneous injection of placebo (group 1) or rHuIL-12 at doses of 50, 100, 250, or 500 ng/kg (groups 2–5, respectively), without antibiotics, fluids or blood transfusions, 24–25 hours after TBI (700 cGy). Results Survival rates at Day 60 were 11%, 33%, 39%, 39%, and 50% for groups 1–5, respectively (log rank p < 0.05 for each dose vs. control). rHuIL-12 also significantly reduced the incidences of severe neutropenia, severe thrombocytopenia, and sepsis (positive hemoculture). Additionally, bone marrow regeneration following TBI was significantly greater in monkeys treated with rHuIL-12 than in controls. Conclusions Data from this study demonstrate that a single injection of rHuIL-12 delivered one day after TBI can significantly increase survival and reduce radiation-induced hematopoietic toxicity and infections. These data significantly advance development of rHuIL-12 toward approval under the Animal Rule as an effective stand-alone medical countermeasure against the lethal effects of radiation exposure. PMID:24708888

  7. Examining lethality risk for rodent studies of primary blast lung injury.

    PubMed

    Hubbard, William Brad; Hall, Christina; Siva Sai Suijith Sajja, Venkata; Lavik, Erink; VandeVord, Pamela

    2014-01-01

    While protective measures have been taken to mitigate injury to the thorax during a blast exposure, primary blast lung injury (PBLI) is still evident in mounted/in vehicle cases during military conflicts. Moreover, civilians, who are unprotected from blast exposure, can be severely harmed by terrorist attacks that use improvised explosive devices (IEDs). Since the lungs are the most susceptible organ due to their air-filled nature, PBLI is one of the most serious injuries seen in civilian blast cases. Determining lethality threshold for rodent studies is crucial to guide experimental designs centered on therapies for survival after PBLI or mechanistic understanding of the injury itself. Using an Advanced Blast Simulator, unprotected rats were exposed to a whole body blast to induce PBLI. The one-hour survival rate was assessed to determine operating conditions for a 50% lethality rate. Macroscopic and histological analysis of lung was conducted using hematoxylin and eosin staining. Results demonstrated lethality risk trends based on static blast overpressure (BOP) for rodent models, which may help standardized animal studies and contribute to scaling to the human level. The need for a standardized method of producing PBLI is pressing and establishing standard curves, such as a lethality risk curve for lung blasts, is crucial for this condensing of BOP methods. PMID:25405409

  8. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  9. Issues surrounding lethal injection as a means of capital punishment.

    PubMed

    Romanelli, Frank; Whisman, Tyler; Fink, Joseph L

    2008-12-01

    Lethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982. Most lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the "medicalization" of execution and the ethics of health care professionals' participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.

  10. Amazing Animals

    ERIC Educational Resources Information Center

    Al-Kuwari, Najat Saad

    2007-01-01

    "Animals" is a three-part lesson plan for young learners with a zoo animal theme. The first lesson is full of activities to describe animals, with Simon Says, guessing games, and learning stations. The second lesson is about desert animals, but other types of animals could be chosen depending on student interest. This lesson teaches…

  11. Antenatal diagnosis of lethal skeletal dysplasias.

    PubMed

    Tretter, A E; Saunders, R C; Meyers, C M; Dungan, J S; Grumbach, K; Sun, C C; Campbell, A B; Wulfsberg, E A

    1998-02-17

    Lethal skeletal dysplasias (LSD) are a heterogeneous group of rare but important genetic disorders characterized by abnormal growth and development of bone and cartilage. We describe the diagnosis and outcome of 29 cases of lethal skeletal dysplasias evaluated between January 1989 and December 1996 at the University of Maryland Medical Center and the Ultrasound Institute of Baltimore. Two cases presented at delivery with no prenatal care while the remaining 27 cases were identified by antenatal sonography. Final diagnoses included thanatophoric dysplasia (14), osteogenesis imperfecta, type II (6), achondrogenesis (2), short rib syndromes (3), campomelic syndrome (2), atelosteogenesis (1), and no evidence of a skeletal dysplasia (1). Twenty out of 27 pregnancies were terminated with an average at detection of 21.6 weeks. The other 7 pregnancies that went on to deliver had an average age at detection of 29.2 weeks. Fetal abnormalities in the terminated pregnancies were identified at a significantly earlier gestational age (P = 0.0016) than the pregnancies that continued. While the identification of LSD by sonography was excellent (26/27), only 13/27 (48%) were given an accurate specific antenatal diagnosis. In 8/14 (57%) cases with an inaccurate or nonspecific diagnosis there was a significant or crucial change in the genetic counseling. Thus, while antenatal sonography is an excellent method for discovering LSD, clinical examination, radiographs, and autopsy are mandatory for making a specific diagnosis. PMID:9489797

  12. Sublethal and potentially lethal damage repair on thermal neutron capture therapy

    SciTech Connect

    Utsumi, H.; Ichihashi, M.; Kobayashi, T.; Elkind, M.M. )

    1989-07-01

    Tonicity shock or caffeine postirradiation treatment makes evident fast-type potentially lethal damage (PLD). Caffeine expresses fast-type PLD more efficiently than tonicity shock in X-irradiated B-16 mouse melanoma cells, compared with V79 Chinese hamster cells. The survival curves of thermal neutrons for either V79 or B-16 cells exhibit no shoulder. Neither V79 nor B-16 cells show the sublethal damage (SLD) repair of thermal neutrons. Caffeine-sensitive fast-type PLD repairs exist in X-irradiated B-16 cells, as well as V79 cells. The fast-type PLD repair of B-16 cells exposed to thermal neutrons alone is rather less than that of X-irradiated cells. Furthermore, an extremely low level of fast-type PLD repair of B-16 cells with 10B1-paraboronophenylalanine (BPA) preincubation (20 hours) followed by thermal neutron irradiation indicated that 10B(n,alpha)7Li reaction effectively eradicates actively growing melanoma cells. The plateau-phase B-16 cells are well able to repair the slow-type PLD of X-rays. However, cells can not repair the slow-type PLD induced by thermal neutron irradiation with or without 10B1-BPA preincubation. These results suggest that thermal neutron capture therapy can effectively kill radioresistant melanoma cells in both proliferating and quiescent phases.

  13. Potential lethal and non-lethal effects of predators on dispersal of spider mites.

    PubMed

    Otsuki, Hatsune; Yano, Shuichi

    2014-11-01

    Predators can affect prey dispersal lethally by direct consumption or non-lethally by making prey hesitate to disperse. These lethal and non-lethal effects are detectable only in systems where prey can disperse between multiple patches. However, most studies have drawn their conclusions concerning the ability of predatory mites to suppress spider mites based on observations of their interactions on a single patch or on heavily infested host plants where spider mites could hardly disperse toward intact patches. In these systems, specialist predatory mites that penetrate protective webs produced by spider mites quickly suppress the spider mites, whereas generalist predators that cannot penetrate the webs were ineffective. By using a connected patch system, we revealed that a generalist ant, Pristomyrmex punctatus Mayr (Hymenoptera: Formicidae), effectively prevented dispersal of spider mites, Tetranychus kanzawai Kishida (Acari: Tetranychidae), by directly consuming dispersing individuals. We also revealed that a generalist predatory mite, Euseius sojaensis Ehara (Acari: Phytoseiidae), prevented between-patch dispersal of T. kanzawai by making them hesitate to disperse. In contrast, a specialist phytoseiid predatory mite, Neoseiulus womersleyi Schicha, allowed spider mites to escape an initial patch, increasing the number of colonized patches within the system. Our results suggest that ants and generalist predatory mites can effectively suppress Tetranychus species under some conditions, and should receive more attention as agents for conservation biological control in agroecosystems.

  14. Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

    ERIC Educational Resources Information Center

    Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

    2004-01-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

  15. Gonadosomatic mosaicism for lethal mutations in Drosophila lethal mutations disturbing larval development

    SciTech Connect

    Ivanov, A.I.; Sakharova, N.Yu.

    1988-11-01

    Phenogenetic analysis of autonomous lethal mutations obtained by the method of gonadosomatic mosaicism which manifested during larval stages, established that the nuclei of hypodermal cells, salivary glands suprapharyngeal ganglion, pharynx, esophagus, gizzard, and hindgut are the derivatives of the same nucleus (from the first two nuclei of cleavage) as the nuclei of the cells of the imaginal-somatic tissues.

  16. High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

    NASA Astrophysics Data System (ADS)

    Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

    2012-07-01

    Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

  17. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    NASA Astrophysics Data System (ADS)

    Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

    2008-12-01

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  18. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    SciTech Connect

    Roszer, Tamas; Pintye, Eva; Benko', Ilona

    2008-12-08

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  19. Synthetic lethal approaches for assessing combinatorial efficacy of chemotherapeutic drugs.

    PubMed

    Jackson, Rebecca A; Chen, Ee Sin

    2016-06-01

    The recent advances in pharmacogenomics have made personalized medicine no longer a pipedream but a precise and powerful way to tailor individualized cancer treatment strategies. Cancer is a devastating disease, and contemporary chemotherapeutic strategies now integrate several agents in the treatment of some types of cancer, with the intent to block more than one target simultaneously. This constitutes the premise of synthetic lethality, an attractive therapeutic strategy already demonstrating clinical success in patients with breast and ovarian cancers. Synthetic lethal combinations offer the potential to also target the hitherto "undruggable" mutations that have challenged the cancer field for decades. However, synthetic lethality in clinical cancer therapy is very much still in its infancy, and selecting the most appropriate combinations-or synthetic lethal pairs-is not always an intuitive process. Here, we review some of the recent progress in identifying synthetic lethal combinations and their potential for therapy and highlight some of the tools through which synthetic lethal pairs are identified.

  20. Hepatobiliary kinetics after whole-body irradiation

    SciTech Connect

    Durakovic, A.

    1986-09-01

    The purpose of this investigation was to study hepatobiliary kinetics after whole-body gamma irradiation. Two groups of nine male beagle dogs were irradiated with a single whole body dose of 4- and 8-Gy cobalt-60 photons. Each animal was injected with 2 mCi Tc-99m DISIDA and scintigraphic studies were obtained with a gamma camera with a parallel hole multipurpose collimator. The parameters studied included: peak activity of the liver and gall bladder and gall bladder and intestinal visualization from the time of Tc-99m DISIDA administration. Total and indirect bilirubin, LDH, SGOT, and SGPT determined as baseline studies before irradiation and at different time intervals after irradiation were not changed in irradiated animals. Whole body Co-60 irradiation with 4 and 8 Gy produced no significant changes in the Tc-99m DISIDA visualization of the gall bladder or in the peak activity in the gall bladder or the liver 1 and 7 days after irradiation. Intestinal visualization occurred significantly earlier in 8 Gy Co-60 irradiated animals on both day 1 and day 7 post irradiation, compared to baseline values where it was never observed before 195.0 minutes. Gall bladder emptying is significantly accelerated after 8 Gy but not after 4-Gy Co-60 gamma irradiation. These observations suggest that gamma irradiation stimulates gall bladder contractility without modifying intrahepatic biliary kinetics.

  1. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    Lim, Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang, Yonggang; Yu, Hsiang-Hsuan M; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose We have previously shown that the anti-malarial agent chloroquine can abrogate the lethal cellular effects of low dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials C57BL/6 mice were irradiated with total of 12.8 Gy delivered at 9.4 cGy/hr. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact the survival of ATM null mice (p=0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to radiation had a significant effect on the survival of normal but not ATM null mice strongly suggesting that the in vivo effect like the in vitro effect is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the

  2. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    SciTech Connect

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  3. Single-hit potentially lethal damage: evidence of its repair in mammalian cells

    SciTech Connect

    Utsumi, H.; Hill, C.K.; Ben-Hur, E.; Elkind, M.M.

    1981-09-01

    Following mid to large doses of X rays, or of fission spectrum neutrons, the repair of potentially lethal damage in V79 Chinese hamster cells can be inhibited by anisotonic phosphate-buffered saline or by medium containing 90% D/sub 2/O. The foregoing post-treatments do not affect the viability of unirradiated cells. Using single synchronized cells irradiated in late S-phase, the most resistant phase of the cell cycle, repair of potentially lethal damage in late S-phase, the most resistant phase of the cell cycle, repair of potentially lethal damage in the single-hit, initially exponential, or small-dose part of the survival curve was examined. The use of synchronized cells avoids misinterpretations due to population heterogeneity. The slope of the small-dose, exponential region of the neutron survival curve is much steeper than that of the x-ray survival curve. Even so, it is demonstrated with post-treatments consisting of hypertonic phosphate-buffered saline, medium containing D/sub 2/O,adiation is connected with their proliferation but not with the migration out from lymphoid organs.

  4. Lethal Toxin is a Critical Determinant of Rapid Mortality in Rodent Models of Clostridium sordellii Endometritis

    PubMed Central

    Hao, Yibai; Senn, Tennille; Opp, Judy; Young, Vincent B.; Thiele, Teri; Srinivas, Geetha; Huang, Steven K.; Aronoff, David M.

    2009-01-01

    The toxigenic anaerobe Clostridium sordellii is an uncommon but highly lethal cause of human infection and toxic shock syndrome, yet few studies have addressed its pathogenetic mechanisms. To better characterize the microbial determinants of rapid death from infection both in vitro and in vivo studies were performed to compare a clinical strain of C. sordellii strain (DA-108), isolated from a patient who survived a disseminated infection unaccompanied by toxic shock syndrome, to a virulent reference strain (ATCC9714). Rodent models of endometrial and peritoneal infection with C. sordellii ATCC9714 were rapidly lethal, while infections with DA-108 were not. Extensive genetic and functional comparisons of virulence factor and toxin expression between these two bacterial strains yielded many similarities, with the noted exception that strain DA-108 lacked the tcsL gene, which encodes the large clostridial glucosyltransferase enzyme lethal toxin (TcsL). The targeted removal by immunoprecipitation of TcsL protected animals from death following injection of crude culture supernatants from strain ATCC9714. Injections of a monoclonal anti-TcsL IgG protected animals from death during C. sordellii ATCC9714 infection, suggesting that such an approach might improve the treatment of patients with C. sordellii-induced toxic shock syndrome. PMID:19527792

  5. Orally Available Small-Molecule Polymerase Inhibitor Cures a Lethal Morbillivirus Infection

    PubMed Central

    Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G. Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

    2014-01-01

    Measles virus (MeV) is a highly infectious morbillivirus responsible for major human morbidity and mortality in the non-vaccinated. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Equally infected ferrets receiving post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic and recovered from infection, while control animals succumbed to the disease. Recovered animals also mounted a robust immune response and were protected against re-challenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found attenuated and transmission impaired compared to the genetic parent. These findings pioneer a path towards an effective morbillivirus therapy that aids measles eradication by synergizing vaccine and therapeutics to close herd immunity gaps due to vaccine refusal. PMID:24739760

  6. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus

    PubMed Central

    Ogg, Monica; Jonsson, Colleen B.; Camp, Jeremy V.; Hooper, Jay W.

    2013-01-01

    Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route. PMID:24217424

  7. Irradiation and food processing.

    PubMed

    Sigurbjörnsson, B; Loaharanu, P

    1989-01-01

    After more than four decades of research and development, food irradiation has been demonstrated to be safe, effective and versatile as a process of food preservation, decontamination or disinfection. Its various applications cover: inhibition of sprouting of root crops; insect disinfestation of stored products, fresh and dried food; shelf-life extension of fresh fruits, vegetables, meat and fish; destruction of parasites and pathogenic micro-organisms in food of animal origin; decontamination of spices and food ingredients, etc. Such applications provide consumers with the increase in variety, volume and value of food. Although regulations on food irradiation in different countries are largely unharmonized, national authorities have shown increasing recognition and acceptance of this technology based on the Codex Standard for Irradiated Foods and its associated Code of Practice. Harmonization of national legislations represents an important prerequisite to international trade in irradiated food. Consumers at large are still not aware of the safety and benefits that food irradiation has to offer. Thus, national and international organizations, food industry, trade associations and consumer unions have important roles to play in introducing this technology based on its scientific values. Public acceptance of food irradiation may be slow at the beginning, but should increase at a faster rate in the foreseeable future when consumers are well informed of the safety and benefits of this technology in comparison with existing ones. Commercial applications of food irradiation has already started in 18 countries at present. The volume of food or ingredients treated on a commercial scale varies from country to country ranging from several tons of spices to hundreds of thousands of tons of grains per annum. With the increasing interest of national authorities and the food industry in applying the process, it is anticipated that some 25 countries will use some 55 commercial

  8. Dangerous marine animals.

    PubMed

    Edmonds, C

    1976-04-01

    Tales of dangerous marine animals have flourished, entwining history, legend and imagination. Man is now demonstrating his remarkable adaptability in returning to the aquatic environment, from which he had his origins, and factual knowledge of marine creatures is surplanting mystery, folklore and fear. There is still cause to fear certain aspects of the underwater world, and the one aspect that still holds sway over public interest is that of dangerous marine animals. There is little justification for this top priority. The kelp beds of San Diego will claim more diving victims than all the marine animals around the United States of America. The cold seas off the English coastline, the tidal currents of Hawaii and the multitude of drowning accidents in water caves of Florida and Australia belittle the relatively few fatalities caused by marine animals. Nevertheless, the latter do cause injury and death, especially in the tropical, subtropical and temperate regions. The Indo-Pacific area seems particularly well endowed with a variety of potentially lethal species, and some of these will be dealt with in this paper.

  9. Lethal photosensitization of biofilm-grown bacteria

    NASA Astrophysics Data System (ADS)

    Wilson, Michael

    1997-12-01

    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  10. Alleged lethal sorcery in East Timor.

    PubMed

    Pollanen, Michael S

    2004-01-01

    A wide range of cultural and social perspectives exists on the concept of sudden and unexpected death. In countries, without a formal system of death investigation, sudden death is shrouded in mysticism often based on traditional belief systems. This cultural perspective on sudden death is often at variance with medical and forensic concepts and may include explanations such as sorcery, magic, and voodoo. In this case report, the postmortem findings in an alleged victim of lethal 'black magic', known as ema halo by the indigenous people of East Timor, is described. The alleged victim died suddenly in front of witnesses. At autopsy, marked dilation of a bicuspid aortic valve with annuloaortic ectasia and a sinus of Valsalva aneurysm was found after exhumation of the body. The findings mitigated the local belief in witchcraft and established a natural manner of death.

  11. Ants defend aphids against lethal disease.

    PubMed

    Nielsen, Charlotte; Agrawal, Anurag A; Hajek, Ann E

    2010-04-23

    Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies.

  12. Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats

    SciTech Connect

    Justesen, D.R.

    1981-10-01

    The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

  13. Collagen defects in lethal perinatal osteogenesis imperfecta.

    PubMed

    Bateman, J F; Chan, D; Mascara, T; Rogers, J G; Cole, W G

    1986-12-15

    Quantitative and qualitative abnormalities of collagen were observed in tissues and fibroblast cultures from 17 consecutive cases of lethal perinatal osteogenesis imperfecta (OI). The content of type I collagen was reduced in OI dermis and bone and the content of type III collagen was also reduced in the dermis. Normal bone contained 99.3% type I and 0.7% type V collagen whereas OI bone contained a lower proportion of type I, a greater proportion of type V and a significant amount of type III collagen. The type III and V collagens appeared to be structurally normal. In contrast, abnormal type I collagen chains, which migrated slowly on electrophoresis, were observed in all babies with OI. Cultured fibroblasts from five babies produced a mixture of normal and abnormal type I collagens; the abnormal collagen was not secreted in two cases and was slowly secreted in the others. Fibroblasts from 12 babies produced only abnormal type I collagens and they were also secreted slowly. The slower electrophoretic migration of the abnormal chains was due to enzymic overmodification of the lysine residues. The distribution of the cyanogen bromide peptides containing the overmodified residues was used to localize the underlying structural abnormalities to three regions of the type I procollagen chains. These regions included the carboxy-propeptide of the pro alpha 1(I)-chain, the helical alpha 1(I) CB7 peptide and the helical alpha 1(I) CB8 and CB3 peptides. In one baby a basic charge mutation was observed in the alpha 1(I) CB7 peptide and in another baby a basic charge mutation was observed in the alpha 1(I) CB8 peptide. The primary defects in lethal perinatal OI appear to reside in the type I collagen chains. Type III and V collagens did not appear to compensate for the deficiency of type I collagen in the tissues.

  14. Monocyte chemotactic protein 1 is released during lethal and sublethal bacteremia in baboons.

    PubMed

    Jansen, P M; van Damme, J; Put, W; de Jong, I W; Taylor, F B; Hack, C E

    1995-06-01

    The chemokine monocyte chemotactic protein 1 (MCP-1) is a cytokine with chemotactic activity specific for mononuclear phagocytes. To investigate the possible involvement of MCP-1 in the pathogenesis of sepsis, its course was studied in baboons challenged intravenously with a sublethal or lethal dose of Escherichia coli. Levels of MCP-1 started to increase in both groups of animals 2 h after injection of E. coli, reaching peak levels 4 and 6 h after a sublethal (186 +/- 21 ng/mL) or a lethal (213 +/- 24 ng/mL) dose, respectively. Levels of MCP-1 correlated significantly with plasma levels of another chemokine, interleukin-8 (IL-8; r = .826. P < .001), suggesting that common stimuli mediate the release of both cytokines in this model.

  15. Transgene-based, female-specific lethality system for genetic sexing of the silkworm, Bombyx mori.

    PubMed

    Tan, Anjiang; Fu, Guoliang; Jin, Li; Guo, Qiuhong; Li, Zhiqian; Niu, Baolong; Meng, Zhiqi; Morrison, Neil I; Alphey, Luke; Huang, Yongping

    2013-04-23

    Transgene-based genetic sexing methods are being developed for insects of agricultural and public health importance. Male-only rearing has long been sought in sericulture because males show superior economic characteristics, such as better fitness, lower food consumption, and higher silk yield. Here we report the establishment of a transgene-based genetic sexing system for the silkworm, Bombyx mori. We developed a construct in which a positive feedback loop regulated by sex-specific alternative splicing leads to high-level expression of the tetracycline-repressible transactivator in females only. Transgenic animals show female-specific lethality during embryonic and early larval stages, leading to male-only cocoons. This transgene-based female-specific lethal system not only has wide application in sericulture, but also has great potential in lepidopteran pest control. PMID:23569267

  16. Nandrolone Plus Moderate Exercise Increases the Susceptibility to Lethal Arrhythmias

    PubMed Central

    Ghorbani Baravati, Hamideh; Joukar, Siyavash; Fathpour, Hossein; Kordestani, Zeinab

    2015-01-01

    Background: Until now, no experimental study has directly assessed the arrhythmogenesis of chronic consumption of anabolic androgenic steroids along with moderate-intensity endurance exercise. Objectives: We evaluated the influence of integration of anabolic androgenic steroids along with moderate-intensity endurance exercise on susceptibility to lethal ventricular arrhythmias in rat. Materials and Methods: The animal groups were as follows: control group (CTL); exercise group (EX) which were under 6 weeks of treadmill exercise; nandrolone group (Nan) which received 5 mg/kg of nandrolone decanoate twice a week; vehicle group (Arach) which received Arachis oil (solvent of nandrolone); trained vehicle group (Arach + Ex); and trained nandrolone group (Nan + Ex). One day after ending of the intervention period, arrhythmia was inducted by intravenous infusion of aconitine and ventricular arrhythmias were recorded. Then malondialdehyde (MDA) and glutathione peroxidase (GPX) of heart tissue were measured. Results: Nandrolone, exercise, and their combination were associated with heart hypertrophy. Exercise could prevent the incremental effect of nandrolone on MDA/GPX ratio. Chronic administration of nandrolone with moderate-intensity endurance exercise had no significant effect on blood pressure, heart rate, and basal electrocardiographic parameters. Combination of nandrolone and exercise significantly increased the incidence of ventricular fibrillation (VF) and reduced the VF latency (P < 0.05). Conclusions: The findings suggest that chronic coadministration of nandrolone with moderate-intensity endurance exercise facilitates the VF occurrence in rat. Complementary studies are needed to elucidate the involved mechanisms of this abnormality. PMID:26396972

  17. Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax.

    PubMed

    Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M

    2015-09-29

    The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay.

  18. Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax

    PubMed Central

    Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M.

    2015-01-01

    The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay. PMID:26426050

  19. Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus).

    PubMed

    Nelson, Michelle; Lever, Mark S; Savage, Victoria L; Salguero, Francisco Javier; Pearce, Peter C; Stevens, Daniel J; Simpson, Andrew J H

    2009-04-01

    Susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (Callithrix jacchus) to determine its suitability as a non-human primate model. Pairs of marmosets were exposed to varying challenge doses of Francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). Lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (CFU). However, precise LD(50) determination was not possible. The model was characterized using a target challenge dose of approximately 100 CFU. Increased core body temperature was the first indicator of disease, at approximately 2.5 days p.c. Overt clinical signs were first observed 12-18 h after the temperature increase. Significantly decreased activity was observed after approximately 3 days. All animals succumbed to infection between 4.5 and 7 days p.c. At postmortem examination, gross pathology was evident in the liver, spleen and lungs of all animals and high bacterial numbers were detected in all the organs assessed. Bacteraemia was demonstrated in all animals postmortem. Histopathological observations included severe suppurative bronchopneumonia, severe multifocal pyogranulomatous hepatitis, splenitis and lymphadenitis. Tularaemia disease progression in the common marmoset therefore appears to be consistent with the disease seen in humans and other animal models. The common marmoset may therefore be considered a suitable model for further studies of inhalational tularaemia.

  20. Syn-lethality: an integrative knowledge base of synthetic lethality towards discovery of selective anticancer therapies.

    PubMed

    Li, Xue-juan; Mishra, Shital K; Wu, Min; Zhang, Fan; Zheng, Jie

    2014-01-01

    Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application.

  1. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.

    PubMed

    Flores, Florita; Hoogenboom, Mia O; Smith, Luke D; Cooper, Timothy F; Abrego, David; Negri, Andrew P

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l(-1) TSS (25 mg cm(-2) day(-1)) for M. aequituberculata and 100 mg l(-1) TSS (83 mg cm(-2) day(-1)) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  2. Syn-Lethality: An Integrative Knowledge Base of Synthetic Lethality towards Discovery of Selective Anticancer Therapies

    PubMed Central

    Li, Xue-juan; Mishra, Shital K.; Wu, Min; Zhang, Fan

    2014-01-01

    Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application. PMID:24864230

  3. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    PubMed Central

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  4. Shape of dose-survival curves for mammalian cells and repair of potentially lethal damage analyzed by hypertonic treatment

    SciTech Connect

    Pohlit, W.; Heyder, I.R.

    1981-09-01

    During the usual procedure of testing cell survival by colony-forming ability, repair of potentially lethal damage (PLD) takes place. By incubating the cells in hypertonic suspension a certain part of this repair can be inhibited, leading to an exponential dose-survival curve as expected from the Poisson distribution of lethal events in the cells. If such a hypertonic treatment is performed after increasing intervals following irradiation with x rays, curves with increasing shoulder length are obtained. Quantitative analysis of the kinetics of this repair shows that PLD is repaired for about 1 h after irradiation by a saturated repair system which eliminates about one lesion per 15 min per cell independent of the applied absorbed dose. PLD not eliminated by this last system is repaired by an unsaturated system with a time constant of several hours. Repair of PLD after x irradiation proceeds quantitatively in this way in plateau-phase cells suspended in a conditioned medium, which seems optimal for such repair. If these cells are suspended after irradiation in normal nutrient medium a certain fraction of the PLD is transformed into irreparable damage. The final survival after repair in nutrient medium is then identical with that obtained by the usual measurement of colony-forming ability on nutrient agar. This indicates that the shoulder in dose-survival curves for plateau phase cells ispartly due to repair of PLD and partly due to manifestation of this damage during repair time.

  5. Presence of Virus Neutralizing Antibodies in Cerebral Spinal Fluid Correlates with Non-Lethal Rabies in Dogs

    PubMed Central

    Leyson, Christina M.; Huang, Chien-tsun; Salyards, Gregory; Harvey, Stephen B.; Chen, Zhenhai; He, Biao; Yang, Yang; Hooper, D. C.; Dietzchold, Berhnard; Fu, Zhen F.

    2013-01-01

    Background Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans. Methodology/Principal Findings Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS. Conclusions/Significance Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection. PMID:24069466

  6. Tissue irradiator

    DOEpatents

    Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

    1975-12-16

    A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in- vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood- carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170.

  7. Animal Bites

    MedlinePlus

    Wild animals usually avoid people. They might attack, however, if they feel threatened, are sick, or are protecting their ... or territory. Attacks by pets are more common. Animal bites rarely are life-threatening, but if they ...

  8. Lethal body burdens of polar narcotics: Chlorophenols

    SciTech Connect

    Wezel, A.P. van; Punte, S.S.; Opperhuizen, A.

    1995-09-01

    The goal of the present study was to measure in fathead minnow (Pimephales promelas) the lethal body burden (LBB) of three chlorophenols that are known as polar narcotic chemicals. The LBBs of the chlorophenols were compared to LBBs of nonpolar narcotic chemicals to consider if the two classes of narcotic chemicals differ on a body burden level. The LBB of the most acidic chlorophenol was measured at two different levels of pH exposure to determine the influence of the degree of ionization on the magnitude of the LBB. Both n-octanol/water partition coefficients and n-hexane/water partition coefficients of the chlorophenols were determined at different pH levels to consider the influence of ionization on the partition coefficient and to determine the importance of a polar group in the organic phase on the partitioning behavior. Partitioning to n-octanol and n-hexane was used as input in a model to simulate the equilibrium partitioning between hydrophobic and nonhydrophobic and target and nontarget compartments in the fish.

  9. Tumor clone dynamics in lethal prostate cancer.

    PubMed

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers.

  10. Radiation-induced cell lethality of samonella typhimurium ATCC 14028: Cooperative effect of hydroxyl radical and oxygen

    SciTech Connect

    Kim, Y.A.; Thayer, D.W.

    1995-10-01

    The lethality of {gamma}-radiation doses of 0.2 to 1.0 kGy for Salmonella typhimurium ATCC 14028 was measured in the presence of air, N{sub 2} and N{sub 2}O and with the hydroxyl radical scavengers formate and polyethylene glycol (PEG), M{sub r} 8,000. Saturation of cell suspensions with either N{sub 2}O or N{sub 2}/N{sub 2}/N{sub 2}O (1:1, v/v) gas was expected to double the number of hydroxyl radicals (OH{center_dot}) and to produce an equivalent increase in lethality, but this did not occur. Adding 10% (v/v) O{sub 2} to either N{sub 2}/N{sub 2}O gas produced approximately the same {gamma}-irradiation lethality for S. typhimurium as did air. Addition of hydroxyl radical scavengers, 40 mM formate and 1.5% (w/v) PEG, significantly reduced the lethality of {gamma} radiation for S. typhimurium in the presence of air but not in the presence of N{sub 2} or N{sub 2}O gases. Membrane-permeable formate provided slightly better protection than nonpermeable PEG. Cells of S. typhimurium grown under anaerobic conditions were more sensitive to radiation, and were less protected by hydroxyl radical scavengers, especially formate, than when cells grown under aerobic conditions were irradiated in the presence of oxygen. Hydroxyl radical scavengers provided no further protection during irradiation in the absence of oxygen. These results indicated that the increased radiation sensitivity of cells grown under anaerobic conditions may be related to superoxide radicals which could increase intercellular damage during irradiation in the presence of oxygen. However, endogenous superoxide dismutase and catalase activities did not protect cells from the radiation-induced lethality of S. typhimurium. Cytoplasmic extracts protected bacterial DNA in vitro in either the presence of absence of oxygen, and no radiation-induced lipid peroxidation of the cellular components was identified by measuring the levels of 2-thiobarbituric acid. 38 refs., 4 figs., 2 tabs.

  11. Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model

    PubMed Central

    Cui, Xizhong; Su, Junwu; Li, Yan; Shiloach, Joseph; Solomon, Steven; Kaufman, Jeanne B.; Mani, Haresh; Fitz, Yvonne; Weng, Jia; Altaweel, Laith; Besch, Virginia; Eichacker, Peter Q.

    2012-01-01

    Objectives The in vivo inflammatory effects of the Bacillus anthracis cell wall are unknown. We therefore investigated these effects in rats and, for comparison, those of known inflammatory stimulants, Staphylococcus aureus cell wall or lipopolysaccharide (LPS). Method and Results Sprague–Dawley rats (n = 103) were challenged with increasing B. anthracis cell wall doses (10, 20, 40, 80, or 160 mg/kg) or diluent (control) as a bolus or 24-h infusion. The three highest bolus doses were lethal (20–64% lethality rates) as were the two highest infused doses (13% with each). Comparisons among lethal or nonlethal doses on other measured parameters were not significantly different, and these were combined for analysis. Over the 24 h after challenge initiation with lethal bolus or infusion, compared to controls, ten inflammatory cytokines and NO levels were increased and circulating neutrophils and platelets decreased (P ≤ 0.05). Changes with lethal doses were greater than changes with nonlethal doses (P ≤ 0.01). Lethal bolus or infusion doses produced hypotension or hypoxemia, respectively (P ≤ 0.05). The effects with B. anthracis cell wall were similar to those of S. aureus cell wall or LPS. However, paradoxically administration of B. anthracis cell wall or LPS decreased the lethality of concurrently administered B. anthracis lethal toxin (P < 0.0001 and 0.04, respectively). Conclusion B. anthracis cell wall has the potential to produce inflammatory injury during anthrax infection clinically. However, understanding why cell wall or LPS paradoxically reduced lethality with lethal toxin may help understand this toxin’s pathogenic effects. PMID:19756496

  12. Evaluation and design of non-lethal laser dazzlers utilizing microcontrollers

    NASA Astrophysics Data System (ADS)

    Richardson, Keith Jack

    Current non-lethal weapons suffer from an inability to meet requirements for uses across many fields and purposes. The safety and effectiveness of these weapons are inadequate. New concepts have provided a weapon utilizing lasers to flashblind a target's visual system. Minimal research and testing have been conducted to investigate the efficiency and safety of these weapons called laser dazzlers. Essentially a laser dazzler is comprised of a laser beam that has been diverged with the use of a lens to expand the beam creating an intensely bright flashlight. All laser dazzlers to date are incapable of adjusting to external conditions automatically. This is important, because the power of these weapons need to change according to distance and light conditions. At long distances, the weapon is rendered useless because the laser beam has become diluted. At near distances, the weapon is too powerful causing permanent damage to the eye because the beam is condensed. Similarly, the eye adapts to brightness by adjusting the pupil size, which effectively limits the amount of light entering the eye. Laser eye damage is determined by the level of irradiance entering the eye. Therefore, a laser dazzler needs the ability to adjust output irradiance to compensate for the distance to the target and ambient light conditions. It was postulated if an innovative laser dazzler design could adjust the laser beam divergence then the irradiance at the eye could be optimized for maximum vision disruption with minimal risk of permanent damage. The young nature of these weapons has lead to the rushed assumptions of laser wavelengths (color) and pulsing frequencies to cause maximum disorientation. Research provided key values of irradiance, wavelength, pulsing frequency and functions for the optical lens system. In order for the laser dazzler to continuously evaluate the external conditions, luminosity and distance sensors were incorporated into the design. A control system was devised to

  13. Data base on animal mortality

    SciTech Connect

    Jones, T.D.

    1987-01-01

    A data base on animal mortality has been compiled. The literature on LD/sub 50/ and the dose-response function for radiation-induced lethality, reflect several inconsistencies - primarily due to dose assignments and to analytical methods and/or mathematical models used. Thus, in order to make the individual experiments which were included in the data base as consistent as possible, an estimate of the uniform dose received by the bone marrow in each treatment group was made so that the interspecies differences are minimized. The LD/sub 50/ was recalculated using a single estimation procedure for all studies for which sufficient experimental data are available. For small animals such as mice, the dose to the hematopoietic system is approximately equal to the treatment dose, but for large animals the marrow dose may be about half of the treatment dose.

  14. Entry, Descent, Landing Animation (Animation)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation

    This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.

  15. Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken.

    PubMed

    Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

    2016-01-01

    The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

  16. Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide.

    PubMed

    Sweeney, Lisa M; Sommerville, Douglas R; Channel, Stephen R

    2014-03-01

    The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C) and duration (t), with TL equaling C(n) × t being a typical form. Hypothetically, any combination of concentration and time that yields the same "toxic load" will give a constant biological response. These formulas have been developed and tested using controlled, constant concentration animal studies, but the validity of applying these assumptions to time-varying concentration profiles has not been tested. Experiments were designed to test the validity of the model under conditions of non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus t profiles was used to evaluate the ability of the model to adequately describe the lethality of HCN under the conditions of non-constant inhalation exposure. The model was found to be applicable under the tested conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.

  17. Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken

    PubMed Central

    Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

    2016-01-01

    The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

  18. Lethal Gram-Negative Bacterial Superinfection in Guinea Pigs Given Bacitracin

    PubMed Central

    Farrar, W. Edmund; Kent, Thomas H.; Elliott, Van B.

    1966-01-01

    Farrar, W. Edmund, Jr. (Walter Reed Army Institute of Research, Washington, D.C.), Thomas H. Kent, and Van B. Elliott. Lethal gram-negative bacterial superinfection in guinea pigs given bacitracin. J. Bacteriol. 92:496–501. 1966.—Oral administration of a single dose of bacitracin (either 2,000 or 10,000 units) was lethal to more than 80% of guinea pigs. Within the first 12 hr, there was a 2,000-fold fall in the number of gram-positive organisms in the cecum. An increase in the number of coliform bacteria in the cecum was demonstrable within 6 hr, and, by 48 hr, these organisms had increased from the normal level of less than 100 per gram to approximately 1 billion per gram. The changes in intestinal bacterial flora were associated with development of a severe cecitis, mild ileitis, and acute regional lymphadenitis. Bacteremia, primarily due to coliform bacteria, was demonstrated in approximately 40% of the animals killed between 72 and 96 hr after administration of bacitracin. Development of this disease syndrome was suppressed by the administration of neomycin and polymyxin B, nonabsorbable antibiotics effective against coliform bacteria. The lethal disease produced by bacitracin in the guinea pig is similar to that produced by penicillin. Images PMID:16562140

  19. Sickness behaviour associated with non-lethal infections in wild primates

    PubMed Central

    Ghai, Ria R.; Fugère, Vincent; Chapman, Colin A.; Goldberg, Tony L.; Davies, T. Jonathan

    2015-01-01

    Non-lethal parasite infections are common in wildlife, but there is little information on their clinical consequences. Here, we pair infection data from a ubiquitous soil-transmitted helminth, the whipworm (genus Trichuris), with activity data from a habituated group of wild red colobus monkeys (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. We use mixed-effect models to examine the relationship between non-lethal parasitism and red colobus behaviour. Our results indicate that red colobus increased resting and decreased more energetically costly behaviours when shedding whipworm eggs in faeces. Temporal patterns of behaviour also changed, with individuals switching behaviour less frequently when whipworm-positive. Feeding frequency did not differ, but red colobus consumption of bark and two plant species from the genus Albizia, which are used locally in traditional medicines, significantly increased when animals were shedding whipworm eggs. These results suggest self-medicative plant use, although additional work is needed to verify this conclusion. Our results indicate sickness behaviours, which are considered an adaptive response by hosts during infection. Induction of sickness behaviour in turn suggests that these primates are clinically sensitive to non-lethal parasite infections. PMID:26311670

  20. Lethal body concentrations and accumulation patterns determine time-dependent toxicity of cadmium in soil arthropods

    SciTech Connect

    Crommentuijn, T.; Doodeman, C.J.A.M.; Doornekamp, A.; Pol, J.J.C. van der; Bedaux, J.J.M.; Gestel, C.A.M. van )

    1994-11-01

    Time-dependent toxicity in bioassays is usually explained in terms of uptake and elimination kinetics of the toxicant. By comparing different species with essentially different accumulation kinetics, a firm test of this concept may be made. This article compares the sensitivity of six soil arthropods, the collembolans Orchesella cincta and Tomocerus minor, the oribatid mite Platynothrus peltifer, the isopods Porcellio scaber and Oniscus asellus, and the diplopod Cylindroiulus britannicus, when exposed to cadmium in the food. Survival was determined at various time intervals; accumulation of cadmium in the animals was measured at one time interval. Kinetic-based toxicity models were fitted to the data, and estimates were obtained for lethal body concentration, uptake rate constant, elimination rate constant, and ultimate LC50. Two different accumulation patterns could be discerned; these were correlated with time-survival relationships. One, species that have the possibility to eliminate cadmium will reach an equilibrium for the internal concentration and also an ultimate LC50. Two, species that are unable to eliminate cadmium but store it in the body will have an ultimate LC50 equal to zero. For these species the time in which the lethal body concentration is reached is more important. Taxonomically related species appeared to have comparable accumulation patterns, but lethal body concentrations differed. It is concluded that knowledge of the accumulation pattern is indispensable for the evaluation of species' sensitivities to toxicants.

  1. ALC/50/ values for some polymeric materials. [Apparent Lethal Concentration fire toxicity

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.; Schneider, J. E.; Kourtides, D. A.; Parker, J. A.

    1978-01-01

    Apparent lethal concentrations for 50 per cent of the test animals within a 30-min exposure period (ALC/50/) were determined for seventeen samples of polymeric materials, using the screening test method. The materials evaluated included resin-glass composites, film composites, and miscellaneous resins. ALC(50) values, based on weight of original sample charged, ranged from 24 to 110 mg/l. Modified phenolic resins seemed to exhibit less toxicity than the baseline epoxy resins. Among the film composites evaluated, only flame modified polyvinyl fluoride appeared to exhibit less toxicity than the baseline polyvinyl fluoride film.

  2. Are high-lethality suicide attempters with bipolar disorder a distinct phenotype?

    PubMed

    Oquendo, Maria A; Carballo, Juan Jose; Rajouria, Namita; Currier, Dianne; Tin, Adrienne; Merville, Jessica; Galfalvy, Hanga C; Sher, Leo; Grunebaum, Michael F; Burke, Ainsley K; Mann, J John

    2009-01-01

    Because Bipolar Disorder (BD) individuals making highly lethal suicide attempts have greater injury burden and risk for suicide, early identification is critical. BD patients were classified as high- or low-lethality attempters. High-lethality attempts required inpatient medical treatment. Mixed effects logistic regression models and permutation analyses examined correlations between lethality, number, and order of attempts. High-lethality attempters reported greater suicidal intent and more previous attempts. Multiple attempters showed no pattern of incremental lethality increase with subsequent attempts, but individuals with early high-lethality attempts more often made high-lethality attempts later. A subset of high-lethality attempters make only high-lethality attempts. However, presence of previous low-lethality attempts does not indicate that risk for more lethal, possibly successful, attempts is reduced.

  3. Irradiation subassembly

    DOEpatents

    Seim, O.S.; Filewicz, E.C.; Hutter, E.

    1973-10-23

    An irradiation subassembly for use in a nuclear reactor is described which includes a bundle of slender elongated irradiation -capsules or fuel elements enclosed by a coolant tube and having yieldable retaining liner between the irradiation capsules and the coolant tube. For a hexagonal bundle surrounded by a hexagonal tube the yieldable retaining liner may consist either of six segments corresponding to the six sides of the tube or three angular segments each corresponding in two adjacent sides of the tube. The sides of adjacent segments abut and are so cut that metal-tometal contact is retained when the volume enclosed by the retaining liner is varied and Springs are provided for urging the segments toward the center of the tube to hold the capsules in a closely packed configuration. (Official Gazette)

  4. Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling.

    PubMed

    Medhora, Meetha; Gao, Feng; Glisch, Chad; Narayanan, Jayashree; Sharma, Ashish; Harmann, Leanne M; Lawlor, Michael W; Snyder, Laura A; Fish, Brian L; Down, Julian D; Moulder, John E; Strande, Jennifer L; Jacobs, Elizabeth R

    2015-03-01

    To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy.

  5. Animal welfare and animal rights.

    PubMed

    Sumner, L W

    1988-05-01

    Animal liberationists tend to divide into two mutually antagonistic camps: animal welfarists, who share a utilitarian moral outlook, and animal rightists, who presuppose a structure of basic rights. However, the gap between these groups tends to be exaggerated by their allegiance to oversimplified versions of their favored moral frameworks. For their part, animal rightists should acknowledge that rights, however basic, are also defeasible by appeals to consequences. Contrariwise, animal welfarists should recognize that rights, however derivative, are capable of constraining appeals to consequences. If both sides move to more defensible theoretical positions, their remaining differences on that level may be compatible with a broad area of convergence on practical issues.

  6. Lethal combat and sex ratio evolution in a parasitoid wasp

    PubMed Central

    Innocent, Tabitha M.; Savage, Joanna; West, Stuart A.; Reece, Sarah E.

    2013-01-01

    Sex allocation theory provides excellent opportunities for testing how behavior and life histories are adjusted in response to environmental variation. One of the most successful areas from this respect is Hamilton’s local mate competition theory. As predicted by theory, a large number of animal species have been shown to adjust their offspring sex ratios (proportion male) conditionally, laying less female-biased sex ratios as the number of females that lay eggs on a patch increases. However, recent studies have shown that this predicted pattern is not followed by 2 parasitoid species in the genus Melittobia, which always produce extremely female-biased sex ratios. A possible explanation for this is that males fight fatally and that males produced by the first female to lay eggs on a patch have a competitive advantage over later emerging males. This scenario would negate the advantage of later females producing a less female-biased sex ratio. Here we examine fatal fighting and sex ratio evolution in another species, Melittobia acasta. We show that females of this species also fail to adjust their offspring sex ratio in response to the number of females laying eggs on a patch. We then show that although earlier emerging males do have an advantage in winning fights, this advantage 1) can be reduced by an interaction with body size, with larger males more likely to win fights and 2) only holds for a brief period around the time at which the younger males emerge from their pupae. This suggests that lethal male combat cannot fully explain the lack of sex ratio shift observed in Melittobia species. We discuss alternative explanations. PMID:24273326

  7. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub

  8. MEDLI Animation

    NASA Video Gallery

    Animation of MEDLI, the Mars Science Laboratory Entry, Descent, and Landing Instrument, which contains multiple sophisticated temperature sensors to measure atmospheric conditions and performance o...

  9. Animal therapy.

    PubMed

    Willis, D A

    1997-01-01

    This article explores the concept of animal therapy. The discussion includes a brief history of animal therapy, its importance, its relationship to rehabilitation, and its usefulness as a tool to influence adaptation, change, power, communication, advocacy, teaching, accountability, responsibility, and locus of control. This theoretical concept is important because of the joy and unconditional love animals can provide their owners. Relationships with animals can promote feelings of self-worth, help offset loneliness, reduce anxiety, provide contact, comfort, security, and the feeling of being needed. PMID:9110848

  10. Animal cytomegaloviruses.

    PubMed Central

    Staczek, J

    1990-01-01

    Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovirus infections. Recent advances in biotechnology have permitted the study of many of the animal cytomegaloviruses in vitro. Consequently, animal cytomegaloviruses can be used as model systems for studying the pathogenesis, immunobiology, and molecular biology of cytomegalovirus-host and cytomegalovirus-cell interactions. PMID:2170830

  11. Survival after total body irradiation: Effects of irradiation of exteriorized small intestine. (Reannouncement with new availability information)

    SciTech Connect

    Vriesendorp, H.M.; Vigneulle, R.M.; Kitto, G.; Pelky, T.; Taylor, P.

    1993-12-31

    Rats receiving lethal irradiation to their exteriorized small intestine with pulsed 18 MVp bremsstrahlung radiation live about 4 days longer than rats receiving a dose of total-body irradiation (TBI) causing intestinal death. The LD50 for intestinal irradiation is approximately 6 Gy higher than the LD50 for intestinal death after TBI. Survival time after exteriorized intestinal irradiation can be decreased, by adding abdominal irradiation. Adding thoracic or pelvic irradiation does not alter survival time. Shielding of large intestine improves survival after irradiation of the rest of the abdomen while the small intestine is also shielded. The kinetics of histological changes in small intestinal tissues implicate the release of humoral factors after irradiation of the abdomen. Radiation injury develops faster in the first (proximal) 40 cm of the small intestine and is expressed predominantly as shortening in villus height. In the last (distal) 40 cm of the small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Irradiation (20 Gy) of the proximal small intestine causes 92 % mortality (median survival 10 days). Irradiation (20 Gy) of the distal small intestine causes 27% mortality (median survival > 30 days). In addition to depletion of crypt stem cells in the small intestine, other issues (humoral factors, irradiated subsection of the small intestine and shielding of the large intestine) appear to influence radiation-induced intestinal mortality.

  12. Irradiated foods

    MedlinePlus

    ... it reduces the risk of food poisoning . Food irradiation is used in many countries. It was first approved in the U.S. to prevent sprouts on white potatoes, and to control insects on wheat and in certain spices and seasonings.

  13. Stage-dependent teratogenic and lethal effects exerted by ultraviolet B radiation on Rhinella (Bufo) arenarum embryos.

    PubMed

    Castañaga, Luis A; Asorey, Cynthia M; Sandoval, María T; Pérez-Coll, Cristina S; Argibay, Teresa I; Herkovits, Jorge

    2009-02-01

    The adverse effects of ultraviolet B radiation from 547.2 to 30,096 J/m2 on morphogenesis, cell differentiation, and lethality of amphibian embryos at six developmental stages were evaluated from 24 up to 168 h postexposure. The ultraviolet B radiation lethal dose 10, 50, and 90 values were obtained for all developmental stages evaluated. The lethal dose 50 values, considered as the dose causing lethality in the 50% of the organisms exposed, in J/m2 at 168 h postexposure, ranged from 2,307 to 18,930; gill circulation and blastula were the most susceptible and resistant stages, respectively. Ultraviolet B radiation caused malformations in all developmental stages but was significantly more teratogenic at the gill circulation and complete operculum stages. Moreover, at the gill circulation stage, even the lowest dose (547.2 J/m2) resulted in malformations to 100% of embryos. The most common malformations were persistent yolk plug, bifid spine, reduced body size, delayed development, asymmetry, microcephaly and anencephaly, tail and body flexures toward the irradiated side, agenesia or partial gill development, abnormal pigment distribution, and hypermotility. The stage-dependent susceptibility to ultraviolet B radiation during amphibian embryogenesis could be explained in the framework of evoecotoxicology, considering ontogenic features as biomarkers of environmental signatures of living forms ancestors during the evolutionary process. The stage-dependent susceptibility to ultraviolet B radiation on Rhinella (Bufo) arenarum embryos for both lethal and teratogenic effects could contribute to a better understanding of the role of the increased ultraviolet B radiation on worldwide amphibian populations decline.

  14. Kindergarten Animation

    ERIC Educational Resources Information Center

    Hinshaw, Craig

    2012-01-01

    Animation is one of the last lessons that come to mind when thinking of kindergarten art. The necessary understanding of sequencing, attention to small, often detailed drawings, and the use of technology all seem more suitable to upper elementary. With today's emphasis on condensing and integrating curriculum, consider developing animation lessons…

  15. Animal Detectives

    ERIC Educational Resources Information Center

    Mulvey, Bridget; Warnock, Carly

    2015-01-01

    During a two-week inquiry-based 5E learning cycle unit, children made observations and inferences to guide their explorations of animal traits and habitats (Bybee 2014). The children became "animal detectives" by studying a live-feed webcam and digital images of wolves in their natural habitat, reading books and online sources about…

  16. Galantamine is a novel post-exposure therapeutic against lethal VX challenge

    SciTech Connect

    Hilmas, Corey J. Poole, Melissa J.; Finneran, Kathryn; Clark, Matthew G.; Williams, Patrick T.

    2009-10-15

    The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 {mu}g/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI)

  17. Differential repair of potentially lethal damage in exponentially growing and quiescent 9L cells

    SciTech Connect

    Mendonca, M.S.; Rodriguez, A.; Alpen, E.L. )

    1990-04-01

    The alteration of potentially lethal damage repair by postirradiation treatment with hypertonic saline (0.5 M PBS) was investigated in exponentially growing and quiescent 9L cells in vitro. A single dose of X rays (8.5 Gy) immediately followed by a 30-min treatment with hypertonic PBS at 37 degrees C reduced the survival of exponentially growing 9L cells by a factor of 13-18 compared to survival of irradiated immediately and delayed-plated cells, while the survival of quiescent cells was reduced by only a factor of 5-8. Survival curves confirmed the relative resistance of the quiescent 9L cells versus exponentially growing 9L cells to X rays plus hypertonic treatment. Both the slope and the shoulder of the survival curve were reduced to a greater extent in exponentially growing cells than in the quiescent cells by hypertonic treatment. The response of quiescent cells cannot be explained by either the duration of hypertonic treatment or the redistribution of the cells into G1 phase. We show that quiescent 9L cells can recover from hypertonically induced potentially lethal damage when incubated under conditions which have been found to delay progression through the cell cycle, and postulate that an altered chromatin structure or an enhanced repair capacity of quiescent 9L cells may be responsible for their resistance.

  18. Size of lethality target in mouse immature oocytes determined with accelerated heavy ions.

    PubMed

    Straume, T; Dobson, R L; Kwan, T C

    1989-01-01

    Mouse immature oocytes were irradiated in vivo with highly charged, heavy ions from the Bevalac accelerator at the Lawrence Berkeley Laboratory. The particles used were 670-MeV/nucleon Si14+, 570-MeV/nucleon Ar18+, and 450-MeV/nucleon Fe26+. The cross-sectional area of the lethality target in these extremely radiosensitive cells was determined from fluence-response curves and information on energy deposition by delta rays. Results indicate a target cross-section larger than that of the nucleus, one which closely approximates the cross-sectional area of the entire oocyte. For 450-MeV/nucleon Fe26+ particles, the predicted target cross-sectional area is 120 +/- 16 microns2, comparing well with the microscopically determined cross-sectional area of 111 +/- 12 microns2 for these cells. The present results are in agreement with our previous target studies which implicate the oocyte plasma membrane.

  19. Size of lethality target in mouse immature oocytes determined with accelerated heavy ions.

    PubMed

    Straume, T; Dobson, R L; Kwan, T C

    1989-01-01

    Mouse immature oocytes were irradiated in vivo with highly charged, heavy ions from the Bevalac accelerator at the Lawrence Berkeley Laboratory. The particles used were 670-MeV/nucleon Si14+, 570-MeV/nucleon Ar18+, and 450-MeV/nucleon Fe26+. The cross-sectional area of the lethality target in these extremely radiosensitive cells was determined from fluence-response curves and information on energy deposition by delta rays. Results indicate a target cross-section larger than that of the nucleus, one which closely approximates the cross-sectional area of the entire oocyte. For 450-MeV/nucleon Fe26+ particles, the predicted target cross-sectional area is 120 +/- 16 microns2, comparing well with the microscopically determined cross-sectional area of 111 +/- 12 microns2 for these cells. The present results are in agreement with our previous target studies which implicate the oocyte plasma membrane. PMID:2657842

  20. Animal experimentation.

    PubMed

    Kolar, Roman

    2006-01-01

    Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

  1. Animal learning.

    PubMed

    Castro, Leyre; Wasserman, Edward A

    2010-01-01

    Pavlov and Thorndike pioneered the experimental study of animal learning and provided psychologists with powerful tools to unveil its underlying mechanisms. Today's research developments and theoretical analyses owe much to the pioneering work of these early investigators. Nevertheless, in the evolution of our knowledge about animal learning, some initial conceptions have been challenged and revised. We first review the original experimental procedures and findings of Pavlov and Thorndike. Next, we discuss critical research and consequent controversies which have greatly shaped animal learning theory. For example, although contiguity seemed to be the only condition that is necessary for learning, we now know that it is not sufficient; the conditioned stimulus (CS) also has to provide information about the occurrence of the unconditioned stimulus (US). Also, animals appear to learn different things about the same stimuli when circumstances vary. For instance, when faced with situations in which the meaning of a CS changes, as in the case of acquisition and later extinction, animals seem to preserve the original knowledge (CS-US) in addition to learning about the new conditions (CS-noUS). Finally, we discuss how parallels among Pavlovian conditioning, operant conditioning, and human causal judgment suggest that causal knowledge may lie at the root of both human and animal learning. All of these empirical findings and theoretical developments prove that animal learning is more complex and intricate than was once imagined. Copyright © 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

  2. Animal learning.

    PubMed

    Castro, Leyre; Wasserman, Edward A

    2010-01-01

    Pavlov and Thorndike pioneered the experimental study of animal learning and provided psychologists with powerful tools to unveil its underlying mechanisms. Today's research developments and theoretical analyses owe much to the pioneering work of these early investigators. Nevertheless, in the evolution of our knowledge about animal learning, some initial conceptions have been challenged and revised. We first review the original experimental procedures and findings of Pavlov and Thorndike. Next, we discuss critical research and consequent controversies which have greatly shaped animal learning theory. For example, although contiguity seemed to be the only condition that is necessary for learning, we now know that it is not sufficient; the conditioned stimulus (CS) also has to provide information about the occurrence of the unconditioned stimulus (US). Also, animals appear to learn different things about the same stimuli when circumstances vary. For instance, when faced with situations in which the meaning of a CS changes, as in the case of acquisition and later extinction, animals seem to preserve the original knowledge (CS-US) in addition to learning about the new conditions (CS-noUS). Finally, we discuss how parallels among Pavlovian conditioning, operant conditioning, and human causal judgment suggest that causal knowledge may lie at the root of both human and animal learning. All of these empirical findings and theoretical developments prove that animal learning is more complex and intricate than was once imagined. Copyright © 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID:26272842

  3. Wild Animals.

    ERIC Educational Resources Information Center

    Web Feet K-8, 2000

    2000-01-01

    This annotated subject guide to Web sites and other resources focuses on wild animals. Includes Web sites, CD-ROMs and software, videos, books, audios, magazines, and professional resources, as well as a class activity. (LRW)

  4. Pulsar Animation

    NASA Video Gallery

    Pulsars are thought to emit relatively narrow radio beams, shown as green in this animation. If these beams don't sweep toward Earth, astronomers cannot detect the radio signals. Pulsar gamma-ray e...

  5. Animal Bites

    MedlinePlus

    ... Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental Disabilities Ear Nose & Throat Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth ...

  6. Suzaku Animation

    NASA Video Gallery

    This animation depicts the Suzaku spacecraft. Suzaku (originally known as Astro-E2) was launched July 10, 2005, and maintains a low-Earth orbit while it observes X-rays from the universe. The satel...

  7. [Dangerous animals].

    PubMed

    Koljonen, Virve; Söderlund, Tim; Mäkisalo, Heikki; Gissler, Mika

    2016-01-01

    Contacts between humans and animals inevitably involve encounters possibly resulting in the human being injured. During the period of 2000 to 2014 almost 90 people died in this kind of conflict in Finland. Of these deaths, one third were associated with horses. In addition, over the same period 85 people died in traffic accidents in which an animal was hit by a car. Accidents requiring hospitalization occurred for approx. 8 000 people. PMID:27522833

  8. Lethal, potentially lethal, and nonlethal damage induction by heavy ions in cultured human cells

    SciTech Connect

    Todd, P.; Wood, J.C.; Walker, J.T.; Weiss, S.J.

    1985-01-01

    In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus.

  9. Empirical complexities in the genetic foundations of lethal mutagenesis.

    PubMed

    Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

    2013-10-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

  10. Chemotherapy agents and the induction of late lethal defects.

    PubMed

    Seymour, C B; Mothersill, C

    1991-01-01

    Radiation is now known to be capable of producing both lethal and non lethal lesions in a variety of mammalian cells which may not be expressed for several cell divisions after the initial insult. The mechanism by which such an effect occurs is unknown. Because of the possible implications for cancer treatment, if such an effect also occurred following chemotherapy exposure, cells were exposed to various cytotoxic chemotherapy agents with known and well characterised effects on DNA or other areas of cell function or structure. The results indicate that late lethal defects are not detectable after treatment with appropriate ranges of doses of cisplatinum, vincristine, BCNU or adriamycin, but that they are induced by Bleomycin and to a lesser extent by 5-Fluorouracil. Bleomycin is known to cause strand breaks and is regarded as a radiomimetic agent. 5-Fluorouracil may act by preventing efficient and faithful synthesis of DNA, allowing mutations to become integrated into the genome. The occurrence of lethal mutations with both these agents supports previous suggestions that error-prone repair of DNA base sequence abnormalities may be fundamental to the process of late lethal damage production in mammalian cells. The cloning efficiency of cells which survived exposure to Vincristine or BCNU over a wide dose range was found to be significantly increased; this may represent an adaptive response to the drugs.

  11. The Rorschach Suicide Constellation: assessing various degrees of lethality.

    PubMed

    Fowler, J C; Piers, C; Hilsenroth, M J; Holdwick, D J; Padawer, J R

    2001-04-01

    In this article we examine the relation between the Rorschach Comprehensive System's Suicide Constellation (S-CON; Exner, 1993; Exner & Wiley, 1977) and lethality of suicide attempts during the course of patients' hospitalization at the Austen Riggs Center (Stockbridge, MA). Patient records were rated as nonsuicidal (n = 37), parasuicidal (n = 37), or near-lethal (n = 30) based on the presence and lethality of self-destructive acts. Diagnostic efficiency statistics utilizing a cutoff score of 7 or more positive indicators successfully predicted which patients would engage in near-lethal suicidal activity relative to parasuicidal patients (overall correct classification rate [OCC] = .79), nonsuicidal inpatients (OCC = .79), and college students (OCC = .89). Although these predictions were influenced by relatively high base rates in the hospital population (14.5%), base rate estimates were calculated for other hypothetical populations revealing different prediction estimates that should be considered when judging the relative efficacy of the S-CON. Logistic regression analysis revealed that an S-CON score of 7 or more was the sole predictor of near-lethal suicide attempts among 9 psychiatric and demographic variables.

  12. The Rorschach Suicide Constellation: assessing various degrees of lethality.

    PubMed

    Fowler, J C; Piers, C; Hilsenroth, M J; Holdwick, D J; Padawer, J R

    2001-04-01

    In this article we examine the relation between the Rorschach Comprehensive System's Suicide Constellation (S-CON; Exner, 1993; Exner & Wiley, 1977) and lethality of suicide attempts during the course of patients' hospitalization at the Austen Riggs Center (Stockbridge, MA). Patient records were rated as nonsuicidal (n = 37), parasuicidal (n = 37), or near-lethal (n = 30) based on the presence and lethality of self-destructive acts. Diagnostic efficiency statistics utilizing a cutoff score of 7 or more positive indicators successfully predicted which patients would engage in near-lethal suicidal activity relative to parasuicidal patients (overall correct classification rate [OCC] = .79), nonsuicidal inpatients (OCC = .79), and college students (OCC = .89). Although these predictions were influenced by relatively high base rates in the hospital population (14.5%), base rate estimates were calculated for other hypothetical populations revealing different prediction estimates that should be considered when judging the relative efficacy of the S-CON. Logistic regression analysis revealed that an S-CON score of 7 or more was the sole predictor of near-lethal suicide attempts among 9 psychiatric and demographic variables. PMID:11393464

  13. Recombinant human manganese superoxide dismutase (rMnSOD): a positive effect on the immunohematological state of mice irradiated with protons

    NASA Astrophysics Data System (ADS)

    Ambesi-Impiombato, Francesco Saverio; Belov, Oleg; Bulinina, Taisia; Ivanov, Alexander; Mancini, Aldo; Borrelli, Antonella; Krasavin, Eugene A.

    Protons represent the largest component of space radiation. In this regard screening of radioprotective drugs capable of increasing radioresistance of astronauts obligatory includes studying these compounds using proton radiation injury models. The recombinant human manganese superoxide dismutase (rMnSOD) had previously demonstrated its efficacy on an in vivo X-ray induced injury model, when multiple intraperitoneal treatments allowed the survival of mice irradiated with doses which were lethal for the control animals (Borrelli A et al. “A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells”. Free Radic Biol Med. 2009, 46, 110-6). Using the model of sublethal whole-body irradiation with protons available at Phasotron of Joint Institute for Nuclear Research (Dubna, Russia), we reconstruct the bone-marrow form of the acute radiation sickness to test the radioprotective effect of rMnSOD. Male (CBAxC57Bl6) F1 hybrid SPF mice weighting approximately 24 g were exposed to 171 MeV protons at the dose of 4 Gy. After irradiation, the sixfold daily subcutaneous treatment with rMnSOD has provided a statistically significant acceleration of the recovery of thymus and spleen mass and of the number of leukocytes in mice peripheral blood. In the control, untreated and irradiated mice, these positive effects were not observed even on day 7 after exposure. The number of karyocytes in bone marrow of irradiated mice has even exceeded its basal level in the control group 7 days after irradiation. The rMnSOD-treated group has thus demonstrated a significant hyper-restoration of this characteristic. In the presentation, several possibilities of using of rMnSOD in space medicine will be discussed, taking into account various biomedically relevant effects of this enzyme.

  14. Animal Bioacoustics

    NASA Astrophysics Data System (ADS)

    Fletcher, Neville H.

    Animals rely upon their acoustic and vibrational senses and abilities to detect the presence of both predators and prey and to communicate with members of the same species. This chapter surveys the physical bases of these abilities and their evolutionary optimization in insects, birds, and other land animals, and in a variety of aquatic animals other than cetaceans, which are treated in Chap. 20. While there are many individual variations, and some animals devote an immense fraction of their time and energy to acoustic communication, there are also many common features in their sound production and in the detection of sounds and vibrations. Excellent treatments of these matters from a biological viewpoint are given in several notable books [19.1,2] and collections of papers [19.3,4,5,6,7,8], together with other more specialized books to be mentioned in the following sections, but treatments from an acoustical viewpoint [19.9] are rare. The main difference between these two approaches is that biological books tend to concentrate on anatomical and physiological details and on behavioral outcomes, while acoustical books use simplified anatomical models and quantitative analysis to model vocalization frequency scaling in animals hearing sound production animal animal biological biological bioacoustics whole-system behavior. This latter is the approach to be adopted here.

  15. Cyclopeptide toxins of lethal amanitas: Compositions, distribution and phylogenetic implication.

    PubMed

    Tang, Shanshan; Zhou, Qian; He, Zhengmi; Luo, Tao; Zhang, Ping; Cai, Qing; Yang, Zhuliang; Chen, Jia; Chen, Zuohong

    2016-09-15

    Lethal amanitas (Amanita sect. Phalloideae) are responsible for 90% of all fatal mushroom poisonings. Since 2000, more than ten new lethal Amanita species have been discovered and some of them had caused severe mushroom poisonings in China. However, the contents and distribution of cyclopeptides in these lethal mushrooms remain poorly known. In this study, the diversity of major cyclopeptide toxins in seven Amanita species from Eastern Asia and three species from Europe and North America were systematically analyzed, and a new approach to inferring phylogenetic relationships using cyclopeptide profile was evaluated for the first time. The results showed that there were diversities of the cyclopeptides among lethal Amanita species, and cyclopeptides from Amanita rimosa and Amanita fuligineoides were reported for the first time. The amounts of amatoxins in East Asian Amanita species were significantly higher than those in European and North American species. The analysis of distribution of amatoxins and phallotoxins in various Amanita species demonstrated that the content of phallotoxins was higher than that of amatoxins in Amanita phalloides and Amanita virosa. In contrast, the content of phallotoxins was significantly lower than that of amatoxins in all East Asian lethal Amanita species tested. However, the distribution of amatoxins and phallotoxins in different tissues showed the same tendency. Eight cyclopeptides and three unknown compounds were identified using cyclopeptide standards and high-resolution MS. Based on the cyclopeptide profiles, phylogenetic relationships of lethal amanitas were inferred through a dendrogram generated by UPGMA method. The results showed high similarity to the phylogeny established previously based on the multi-locus DNA sequences. PMID:27476461

  16. A lethal disease model for hantavirus pulmonary syndrome in immunosuppressed Syrian hamsters infected with Sin Nombre virus.

    PubMed

    Brocato, Rebecca L; Hammerbeck, Christopher D; Bell, Todd M; Wells, Jay B; Queen, Laurie A; Hooper, Jay W

    2014-01-01

    Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.

  17. Lethal toxicity of cadmium to Cyprinus carpio and Tilapia aurea

    SciTech Connect

    Not Available

    1986-09-01

    There have been several studies of the lethal toxicity of cadmium to freshwater fishes, but further information is required on a number of points. For example, the shallow slope which is characteristic of the cadmium toxicity curve makes interspecific comparisons difficult. There also is a paucity of information on cadmium toxicity to non-Salmonid European species. As part of a study of the water quality requirements of cultured fish species in the Mediterranean, the authors report on the lethal toxicity of cadmium to two such species, the common carp Cyprinus carpio, and Tilapia aurea, for which little information has previously been reported.

  18. Approaches to Identifying Synthetic Lethal Interactions in Cancer

    PubMed Central

    Thompson, Jordan M.; Nguyen, Quy H.; Singh, Manpreet; Razorenova, Olga V.

    2015-01-01

    Targeting synthetic lethal interactions is a promising new therapeutic approach to exploit specific changes that occur within cancer cells. Multiple approaches to investigate these interactions have been developed and successfully implemented, including chemical, siRNA, shRNA, and CRISPR library screens. Genome-wide computational approaches, such as DAISY, also have been successful in predicting synthetic lethal interactions from both cancer cell lines and patient samples. Each approach has its advantages and disadvantages that need to be considered depending on the cancer type and its molecular alterations. This review discusses these approaches and examines case studies that highlight their use. PMID:26029013

  19. Animal Identification

    PubMed Central

    Macpherson, J. W.; Penner, P.

    1967-01-01

    A number of branding tools of various metals and various sizes in combination with several wetting agents were cooled with liquid nitrogen and applied for different lengths of time to calves and mature cattle. White hair appeared in the shape of the brand on the animals in place of dark hair when the application was properly carried out. Best results can be obtained by using metal irons at least 25 millimeters thick and 14 millimeters wide with xylol as a wetting agent for ten seconds in young or thin skinned animals and up to twenty seconds in mature or thick skinned animals. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 5. PMID:4229181

  20. Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening

    PubMed Central

    Adams, David; Baldock, Richard; Bhattacharya, Shoumo; Copp, Andrew J.; Dickinson, Mary; Greene, Nicholas D. E.; Henkelman, Mark; Justice, Monica; Mohun, Timothy; Murray, Stephen A.; Pauws, Erwin; Raess, Michael; Rossant, Janet; Weaver, Tom; West, David

    2013-01-01

    Identifying genes that are important for embryo development is a crucial first step towards understanding their many functions in driving the ordered growth, differentiation and organogenesis of embryos. It can also shed light on the origins of developmental disease and congenital abnormalities. Current international efforts to examine gene function in the mouse provide a unique opportunity to pinpoint genes that are involved in embryogenesis, owing to the emergence of embryonic lethal knockout mutants. Through internationally coordinated efforts, the International Knockout Mouse Consortium (IKMC) has generated a public resource of mouse knockout strains and, in April 2012, the International Mouse Phenotyping Consortium (IMPC), supported by the EU InfraCoMP programme, convened a workshop to discuss developing a phenotyping pipeline for the investigation of embryonic lethal knockout lines. This workshop brought together over 100 scientists, from 13 countries, who are working in the academic and commercial research sectors, including experts and opinion leaders in the fields of embryology, animal imaging, data capture, quality control and annotation, high-throughput mouse production, phenotyping, and reporter gene analysis. This article summarises the outcome of the workshop, including (1) the vital scientific importance of phenotyping embryonic lethal mouse strains for basic and translational research; (2) a common framework to harmonise international efforts within this context; (3) the types of phenotyping that are likely to be most appropriate for systematic use, with a focus on 3D embryo imaging; (4) the importance of centralising data in a standardised form to facilitate data mining; and (5) the development of online tools to allow open access to and dissemination of the phenotyping data. PMID:23519032

  1. Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome

    PubMed Central

    Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

    2015-01-01

    KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. PMID:26166481

  2. Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome.

    PubMed

    Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

    2015-08-01

    KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. PMID:26166481

  3. Abnormal differentiation, hyperplasia and embryonic/perinatal lethality in BK5-T/t transgenic mice

    PubMed Central

    Chen, Xin; Schneider-Broussard, Robin; Hollowell, Debra; McArthur, Mark; Jeter, Collene R.; Benavides, Fernando; DiGiovanni, John; Tang, Dean G.

    2009-01-01

    The cell-of-origin has a great impact on the types of tumors that develop and the stem/progenitor cells have long been considered main targets of malignant transformation. The SV40 large T and small t antigens (T/t), have been targeted to multiple differentiated cellular compartments in transgenic mice. In most of these studies, transgenic animals develop tumors without apparent defects in animal development. In this study, we used the bovine keratin 5 (BK5) promoter to target the T/t antigens to stem/progenitor cell-containing cytokeratin 5 (CK5) cellular compartment. A transgene construct, BK5-T/t, was made and microinjected into the male pronucleus of FVB/N mouse oocytes. After implanting ∼1700 embryos, only 7 transgenics were obtained, including 4 embryos (E9.5, E13, E15, and E20) and 3 postnatal animals, which died at P1, P2, and P18, respectively. Immunohistological analysis revealed aberrant differentiation and prominent hyperplasia in several transgenic CK5 tissues, especially the upper digestive organs (tongue, oral mucosa, esophagus, and forestomach) and epidermis, the latter of which also showed focal dysplasia. Altogether, these results indicate that constitutive expression of the T/t antigens in CK5 cellular compartment results in abnormal epithelial differentiation and leads to embryonic/perinatal animal lethality. PMID:19272531

  4. Parenteral Administration of Capsule Depolymerase EnvD Prevents Lethal Inhalation Anthrax Infection.

    PubMed

    Negus, David; Vipond, Julia; Hatch, Graham J; Rayner, Emma L; Taylor, Peter W

    2015-12-01

    Left untreated, inhalation anthrax is usually fatal. Vegetative forms of Bacillus anthracis survive in blood and tissues during infection due to elaboration of a protective poly-γ-D-glutamic acid (PDGA) capsule that permits uncontrolled bacterial growth in vivo, eventually leading to overwhelming bacillosis and death. As a measure to counter threats from multidrug-resistant strains, we are evaluating the prophylactic and therapeutic potential of the PDGA depolymerase EnvD, a stable and potent enzyme which rapidly and selectively removes the capsule from the surface of vegetative cells. Repeated intravenous administration of 10 mg/kg recombinant EnvD (rEnvD) to mice infected with lethal doses of B. anthracis Ames spores by inhalation prevented the emergence of symptoms of anthrax and death; all animals survived the 5-day treatment period, and 70% survived to the end of the 14-day observation period. In contrast to results in sham-treated animals, the lungs and spleen of rEnvD-dosed animals were free of gross pathological changes. We conclude that rEnvD has potential as an agent to prevent the emergence of inhalation anthrax in infected animals and is likely to be effective against drug-resistant forms of the pathogen.

  5. Animal Science.

    ERIC Educational Resources Information Center

    VanCleave, Janice

    2001-01-01

    Presents a set of hands-on, outdoor science experiments designed to teach elementary school students about animal adaptation. The experiments focus on: how color camouflage affects an insect population; how spiderlings find a home; and how chameleons camouflage themselves by changing color. (SM)

  6. Curriculum Animation

    ERIC Educational Resources Information Center

    Gose, Michael D.

    2004-01-01

    Twenty-five teachers with reputations for artistry in curriculum planning were interviewed about their "curriculum animation" plans or how they ensured their curriculum was brought to life. Their statements indicated that much of their planning is informal and intuitive, and that the criteria they use for their curriculum includes: (1) it is…

  7. Transgenic Animals.

    ERIC Educational Resources Information Center

    Jaenisch, Rudolf

    1988-01-01

    Describes three methods and their advantages and disadvantages for introducing genes into animals. Discusses the predictability and tissue-specificity of the injected genes. Outlines the applications of transgenic technology for studying gene expression, the early stages of mammalian development, mutations, and the molecular nature of chromosomes.…

  8. Small Molecule Inhibitors of Anthrax Lethal Factor Toxin

    PubMed Central

    Williams, John D.; Khan, Atiyya R.; Cardinale, Steven C.; Butler, Michelle M.; Bowlin, Terry L.; Peet, Norton P.

    2014-01-01

    This manuscript describes the preparation of new small molecule inhibitors of Bacillus anthracis lethal factor. Our starting point was the symmetrical, bis-quinolinyl compound 1 (NSC 12155). Optimization of one half of this molecule led to new LF inhibitors that were desymmetrized to afford more drug-like compounds. PMID:24290062

  9. Dominant-lethal mutations and heritable translocations in mice

    SciTech Connect

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  10. The "Lethal Chamber": Further Evidence of the Euthanasia Option.

    ERIC Educational Resources Information Center

    Elks, Martin A.

    1993-01-01

    Historical discussions of the euthanasia or "lethal chamber" option in relation to people with mental retardation are presented. The paper concludes that eugenic beliefs in the primacy of heredity over environment and the positive role of natural selection may have condoned the poor conditions characteristic of large, segregated institutions and…

  11. The Prevalence, Lethality and Intent of Suicide Attempts among Adolescents.

    ERIC Educational Resources Information Center

    Andrews, Judy A.; Lewinsohn, Peter M.

    Although suicide is the second leading cause of death among adolescents in the United States, little is known about the prevalence or characteristics of suicide attempts among adolescents. Data from 1,710 adolescents attending 9 high schools in 5 communities were examined to determine the prevalence of suicide attempts and the lethality and intent…

  12. An overview of the future of non-lethal weapons.

    PubMed

    Alexander, J B

    2001-01-01

    During the past decade, vast changes have occurred in the geopolitical landscape and the nature of the types of conflicts in which technologically developed countries have been involved. While the threat of conventional war remains, forces have been more frequently deployed in situations that require great restraint. Adversaries are often likely to be elusive and commingled with noncombatants. There has been some shift in public opinion away from tolerance of collateral casualties. Therefore there is a need to be able to apply force while limiting casualties. Non-lethal weapons provide part of the solution. Among the changes that will influence the future have been studies by the US and NATO concerning the use of non-lethal weapons, coincidental with increased funding for their development and testing. New concepts and policies have recently been formalized. Surprisingly, the most strident objections to the implementation of non-lethal weapons have come from organizations that are ostensibly designed to protect non-combatants. These arguments are specious and, while technically and academically challenging, actually serve to foster an environment that will result in the deaths of many more innocent civilians. They misconstrue technology with human intent. The reasons for use of force will not abate. Alternatives to bombs, missiles, tanks and artillery must therefore be found. Non-lethal weapons are not a panacea but do offer the best hope of minimizing casualties while allowing nations or alliances the means to use force in protection of national or regional interests.

  13. Histopathological effects of anthrax lethal factor on rat liver.

    PubMed

    Altunkaynak, Berrin Zuhal; Ozbek, Elvan

    2015-01-01

    Bacillus anthracis, the causative agent of anthrax, has become an increasingly important scientific topic due to its potential role in bioterrorism. The lethal toxin (LT) of B. anthracis consists of lethal factor (LF) and a protective antigen (PA). This study investigated whether only lethal factor was efficient as a hepatotoxin in the absence of the PA. To achieve this aim, LF (100 µg/kg body weight, dissolved in sterile distilled water) or distilled water vehicle were intraperitoneally injected once into adult rats. At 24 h post-injection, the hosts were euthanized and their livers removed and tissue samples examined under light and electron microscopes. As a result of LF application, hepatic injury - including cytoplasmic and nuclear damage in hepatocytes, sinusoidal dilatation, and hepatocellular lysis - became apparent. Further, light microscopic analyses of liver sections from the LF-injected rats revealed ballooning degeneration and cytoplasmic loss within hepatocytes, as well as peri-sinusoidal inflammation. Additionally, an increase in the numbers of Kupffer cells was evident. Common vascular injuries were also found in the liver samples; these injuries caused hypoxia and pathological changes. In addition, some cytoplasmic and nuclear changes were detected within the liver ultrastructure. The results of these studies allow one to suggest that LF could be an effective toxicant alone and that PA might act in situ to modify the effect of this agent (or the reverse situation wherein LF modifies effects of PA) such that lethality results.

  14. Moving ahead on harnessing synthetic lethality to fight cancer.

    PubMed

    Jerby-Arnon, Livnat; Ruppin, Eytan

    2015-01-01

    We have recently developed a data-mining pipeline that comprehensively identifies cancer unique susceptibilities, following the concept of Synthetic Lethality (SL). The approach enables, for the first time, to identify and harness genome-scale SL-networks to accurately predict gene essentiality, drug response, and clinical prognosis in cancer.

  15. An overview of the future of non-lethal weapons.

    PubMed

    Alexander, J B

    2001-01-01

    During the past decade, vast changes have occurred in the geopolitical landscape and the nature of the types of conflicts in which technologically developed countries have been involved. While the threat of conventional war remains, forces have been more frequently deployed in situations that require great restraint. Adversaries are often likely to be elusive and commingled with noncombatants. There has been some shift in public opinion away from tolerance of collateral casualties. Therefore there is a need to be able to apply force while limiting casualties. Non-lethal weapons provide part of the solution. Among the changes that will influence the future have been studies by the US and NATO concerning the use of non-lethal weapons, coincidental with increased funding for their development and testing. New concepts and policies have recently been formalized. Surprisingly, the most strident objections to the implementation of non-lethal weapons have come from organizations that are ostensibly designed to protect non-combatants. These arguments are specious and, while technically and academically challenging, actually serve to foster an environment that will result in the deaths of many more innocent civilians. They misconstrue technology with human intent. The reasons for use of force will not abate. Alternatives to bombs, missiles, tanks and artillery must therefore be found. Non-lethal weapons are not a panacea but do offer the best hope of minimizing casualties while allowing nations or alliances the means to use force in protection of national or regional interests. PMID:11578037

  16. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... result, one of which is a statistically significant dose-related increase in the number of dominant... a statistically significant dose-related increase in the number of dominant lethals or a... of the uteri are examined to determine the numbers of implants and live and dead embryos....

  17. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... result, one of which is a statistically significant dose-related increase in the number of dominant... a statistically significant dose-related increase in the number of dominant lethals or a... of the uteri are examined to determine the numbers of implants and live and dead embryos....

  18. The Lethal "Femme Fatale" in the Noir Tradition.

    ERIC Educational Resources Information Center

    Boozer, Jack

    2000-01-01

    Traces the lethal seductress through Hollywood's "noir" history from "Double Indemnity" (1944) to "The Last Seduction" (1996). Examines how this figure largely abjures traditional romance and passive domesticity, choosing instead to apply her sexuality to homicidal plots toward greed. Argues that her narrative positioning serves as a barometer of…

  19. Conditional lethality strains for the biological control of Anastrepha species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pro-apoptotic cell death genes are promising candidates for biologically-based autocidal control of pest insects as demonstrated by tetracycline (tet)-suppressible systems for conditional embryonic lethality in Drosophila melanogaster (Dm) and the medfly, Ceratitis capitata (Cc). However, for medfly...

  20. Development of a non-lethal method for evaluating transcriptomic endpoints in Arctic grayling (Thymallus arcticus).

    PubMed

    Veldhoen, Nik; Beckerton, Jean E; Mackenzie-Grieve, Jody; Stevenson, Mitchel R; Truelson, Robert L; Helbing, Caren C

    2014-07-01

    With increases in active mining and continued discharge associated with former mine operations, evaluating the health of watersheds in the Canadian Yukon Territory is warranted. Current environmental assessment approaches often employ guidelines established using sentinel species not relevant to Arctic monitoring programs. The present study focused on the successful development of a quantitative real-time polymerase chain reaction (qPCR) assay directed towards the indigenous Arctic grayling (Thymallus arcticus) and examines the feasibility of using non-lethal sampling from the caudal fin as a means for evaluation of mRNA abundance profiles reflective of environmental conditions. In a proof of concept study performed blind, qPCR results from animals in an area with elevated water concentrations of cadmium (Cd) and zinc (Zn) and higher body burdens of Cd, Zn, and lead (Pb) were compared to a reference location in the Yukon Territory. Lower condition factor and a higher abundance of hepatic and caudal fin gene transcripts encoding the metallothionein isoforms (mta/mtb), in addition to elevated heat shock protein 70 (hsp70) and catalase (cat) mRNAs in liver, were observed in fish from the test site. The strong positive correlation between metal body burden and caudal fin mta/mtb mRNA abundance demonstrates a high potential for use of the Arctic grayling assay in non-lethal environmental monitoring programs.

  1. Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis.

    PubMed

    Wang, Zeneng; Roberts, Adam B; Buffa, Jennifer A; Levison, Bruce S; Zhu, Weifei; Org, Elin; Gu, Xiaodong; Huang, Ying; Zamanian-Daryoush, Maryam; Culley, Miranda K; DiDonato, Anthony J; Fu, Xiaoming; Hazen, Jennie E; Krajcik, Daniel; DiDonato, Joseph A; Lusis, Aldons J; Hazen, Stanley L

    2015-12-17

    Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e(-/-) mice without alterations in circulating cholesterol levels. The present studies suggest that targeting gut microbial production of TMA specifically and non-lethal microbial inhibitors in general may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases.

  2. Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

    PubMed

    Chang, Hsin-Hou; Wang, Tsung-Pao; Chen, Po-Kong; Lin, Yo-Yin; Liao, Chih-Hsien; Lin, Ting-Kai; Chiang, Ya-Wen; Lin, Wen-Bin; Chiang, Chih-Yu; Kau, Jyh-Hwa; Huang, Hsin-Hsien; Hsu, Hui-Ling; Liao, Chi-Yuan; Sun, Der-Shan

    2013-01-01

    Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+)-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

  3. Suppressed Production of Methyl Farnesoid Hormones Yields Developmental Defects and Lethality in Drosophila Larvae

    PubMed Central

    Jones, Davy; Jones, Grace; Teal, Peter; Hammac, Courey; Messmer, Lexa; Osborne, Kara; Belgacem, Yasser Hadj; Martin, Jean-Rene

    2010-01-01

    A long-unresolved question in the developmental biology of Drosophila melanogaster has been whether methyl farnesoid hormones secreted by the ring gland are necessary for larval maturation and metamorphosis. In the present study, we have used RNAi techniques to inhibit 3-Hydroxy-3-Methylglutaryl CoA Reductase (HMGCR) expression selectively in the corpora allatal cells that produce the circulating farnesoid hormones. The developing larvae manifest a number of developmental, metabolic and morphogenetic derangements. These defects included the exhibition of an “ultraspiracle” death phenotype at the 1st to 2nd larval molt, similar to that exhibited by animals that are null for the farnesoid receptor ultraspiracle. The few larvae surviving past a second lethal period at the 2nd to 3rd instar larval molt, again with “ultraspiracle” phenotype, often became developmentally arrested after either attaining a misformed puparium or after formation of the white pupa. Survival past the “ultraspiracle” lethal phenotype could be rescued by dietary provision of an endogenous dedicated precursor to the three naturally secreted methyl farnesoid hormones. In addition to these developmental and morphogenetic defects, most larvae that survived to the late second instar exhibited a posterior-originating melanization of the tracheal system. These results support the hypothesis that larval methyl farnesoid hormones are necessary for larval survival and morphogenetic transformation through the larval and pupal metamorphic processes. PMID:19595690

  4. A conditionally lethal mutant of Salmonella Typhimurium induces a protective response in mice.

    PubMed

    Hidalgo, Alejandro A; Villagra, Nicolás A; Jerez, Sebastián A; Fuentes, Juan A; Mora, Guido C

    2016-02-01

    Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 10(6) bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 10(6) bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 10(4) oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions.

  5. Human cathepsin L rescues the neurodegeneration and lethality incathepsin B/L double deficient mice

    SciTech Connect

    Sevenich, Lisa; Pennacchio, Len A.; Peters, Christoph; Reinheckel, Thomas

    2006-01-09

    Cathepsin B (CTSB) and cathepsin L (CTSL) are two widelyexpressed cysteine proteases thought to predominantly reside withinlysosomes. Functional analysis of CTSL in humans is complicated by theexistence of two CTSL-like homologues (CTSL and CTSL2), in contrast tomice which contain only one CTSL enzyme. Thus transgenic expression ofhuman CTSL in CTSL deficient mice provides an opportunity to study the invivo functions of this human protease without interference by its highlyrelated homologue. While mice with single gene deficiencies for murineCTSB or CTSL survive without apparent neuromuscular impairment, murineCTSB/CTSL double deficient mice display degeneration of cerebellarPurkinje cells and neurons of the cerebral cortex, resulting in severehypotrophy, motility defects, and lethality during their third to fourthweek of life. Here we show that expression of human CTSL through agenomic transgene results in widespread expression of human CTSL in themouse which is capable of rescuing the lethality found in CTSB/CTSLdouble-deficient animals. Human CTSL is expressed in the brain of thesecompound mutants predominantly in neurons of the cerebral cortex and inPurkinje cells of the cerebellum, where it appears to prevent neuronalcell death.

  6. A comparison of irradiation and mitomycin as blocking agents in the mixed lymphocyte reaction

    SciTech Connect

    Anderson, R.E.; Pogue, L.; Troup, G.M.; Standefer, J.C.

    1984-05-01

    In comparison with administration of mitomycin, lethal irradiation (2,000 rad) of the stimulator cells in a one-way mixed leukocyte culture results in a reduced response due at least in part to the release of inhibitory materials by the irradiated cells. These inhibitory molecules may be partially removed by washing and possess differential reactivity with respect to phytohemagglutinin, concanavalin A, lipopolysaccharide, and pokeweed mitogen.

  7. Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

    SciTech Connect

    von Melchner, H.; Metcalf, D.; Mandel, T.E.

    1980-11-01

    After lethal irradiation of C57BL mice followed by the injection of 10/sup 7/ marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 h after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.

  8. Reproductive and genetic effects of continuous prenatal irradiation in the pig

    SciTech Connect

    Erickson, B.H.; Martin, P.G.

    1984-08-01

    The stem germ cells of the prenatal pig are highly vulnerable to the cytotoxic effects of ionizing irradiation. This study was conducted to determine whether sensitivity to killing was also marked by a sensitivity to mutation and how prenatal depletion of the germ-cell population affects reproductive performance. Germ-cell populations were reduced by continuously irradiating sows at dose rates of either 0.25 or 1.0 rad/day for the first 108 days of gestation. The prenatally irradiated boars were tested for sperm-producing ability, sperm abnormalities, dominant lethality, reciprocal translocations, and fertility. Prenatally irradiated females were allowed to bear and nurture one litter, then tested for dominant lethality in a second litter; germ cell survival and follicular development were assessed in their serially sectioned ovaries. Sperm production was not significantly affected in the 0.25-rad boars, but boars irradiated with 1.0 rad per day produced sperm at only 17% of the control level. Incidence of defective sperm was 4.9% and 11.1% in the 0.25 and 1.0 groups, respectively. Four of the 1.0-rad boars were infertile, but prenatal irradiation apparently caused neither dominant lethality nor reciprocal translocations in fertile males. Number of oocytes was reduced to 66 +/- 7% of control in the 0.25-rad gilts, but reproductive performance was unaffected and no dominant lethality was observed. Only 7 +/- 1% of the oocytes survived in the 1.0-rad group. Reproductive performance was normal for the first litter, but four of the 23 sows tested were infertile at the second litter and a significant incidence of dominant lethality was observed.

  9. [Changes in the content of the thiol form of the acetylation coenzyme in the liver during administration of vitamin B3-active compounds to intact and locally irradiated animals].

    PubMed

    Rozanov, V A

    1984-01-01

    A local exposure of mouse head to gamma-rays caused phase changes in CoASH content of the liver. The administration of D-pantothenate-Ca and D-pantethine increased the level of CoASH in the liver of exposed animals; calcium D-homopantothenate did not influence the co-enzyme content. It is suggested that pantothenate and pantethine act like vitamins while the influence of homopantothenate is associated with the effects of calcium ions. PMID:6739738

  10. Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants

    PubMed Central

    Liu, Yuanli; Zhou, Jinan; Qu, Yilin; Yang, Xinguang; Shi, Guojing; Wang, Xiuhong; Hong, Yuzhi; Drlica, Karl; Zhao, Xilin

    2016-01-01

    Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical) are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS) characteristic of treatment with quinolone (oxolinic acid). These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold) the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability. PMID:27045517

  11. Protection against lethal measles virus infection in mice by immune-stimulating complexes containing the hemagglutinin or fusion protein.

    PubMed Central

    Varsanyi, T M; Morein, B; Löve, A; Norrby, E

    1987-01-01

    The importance of each of the two surface glycoproteins of measles virus in active and passive immunization was examined in mice. Infected-cell lysates were depleted of either the hemagglutinin (H) or fusion (F) glycoprotein by using multiple cycles of immunoaffinity chromatography. The products were used to prepare immune-stimulating complexes (iscoms) containing either F or H glycoprotein. Such complexes are highly immunogenic, possibly as a result of effective presentation of viral proteins to the immune system [B. Morein, B. Sundquist, S. Höglund, K. Dalsgaard, and A. Osterhaus, Nature (London) 308:457-460, 1984]. Groups of 3-week-old BALB/c mice were inoculated with the iscom preparations. All animals developed hemolysis-inhibiting antibodies, whereas only sera of animals immunized with the iscoms containing the H glycoprotein had hemagglutination-inhibiting antibodies. Sera from animals immunized with the H or F preparation only precipitated the homologous glycoprotein in radioimmune precipitation assays. The immunized animals were challenged with a lethal dose of the hamster neurotropic variant of measles virus. Of the 7-week-old animals in the nonimmunized control group, 50% died within 10 days after challenge. No animals in the immunized groups showed symptoms of disease throughout the observation period of 3 months. Passive administration of anti-H monoclonal antibodies gave full protection against the 100% lethal acute infection with the hamster neurotropic variant of measles virus in newborn mice, whereas anti-F monoclonal antibodies failed to protect the animals. This study emphasizes that both H and F glycoproteins need to be considered in the development of measles virus subunit vaccines. Images PMID:2960833

  12. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    PubMed

    Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  13. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    PubMed

    Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  14. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

    PubMed Central

    Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  15. Animal leptospirosis.

    PubMed

    Ellis, William A

    2015-01-01

    Leptospirosis is a global disease of animals, which can have a major economic impact on livestock industries and is an important zoonosis. The current knowledge base is heavily biased towards the developed agricultural economies. The disease situation in the developing economies presents a major challenge as humans and animals frequently live in close association. The severity of disease varies with the infecting serovar and the affected species, but there are many common aspects across the species; for example, the acute phase of infection is mostly sub-clinical and the greatest economic losses arise from chronic infection causing reproductive wastage. The principles of, and tests for, diagnosis, treatment, control and surveillance are applicable across the species. PMID:25388134

  16. Robotic animation

    NASA Astrophysics Data System (ADS)

    Kretch, S. J.

    1982-08-01

    The effectiveness of the robotic systems Place and Animate at McDonnell Douglas is discussed. The systems are designed for CAD/CAM on a kinematic basis. Place allows creation, analysis, and editing of cell descriptions as part of the CAD process, and involves primitive cell configuring prior to eventual integration of the entire robot. Objects are displayed in wire frame form and movement receives an awkwardness rating automatically, indicating the percentage of the real-world joint limit that is being approached. The same program is employed in the Animate process, where verification and debugging of the robot programs proceeds. Clearances, motion limits, and correct responses to commands are checked, allowing decisions on production to be made before any robots are actually built.

  17. Sub-lethal cadmium exposure increases phytochelatin concentrations in the aquatic snail Lymnaea stagnalis.

    PubMed

    Sf, Gonçalves; Sk, Davies; Bennett, M; Raab, A; Feldmann, J; Kille, P; Loureiro, S; Dj, Spurgeon; Jg, Bundy

    2016-10-15

    Phytochelatins are metal-binding metabolites found in almost all plant species and some animal groups, including nematodes and annelids, where they can play an important role in detoxifying metals such as cadmium. Species from several other taxa contain a phytochelatin synthase (PCS) gene orthologue, including molluscs, indicating they may have the potential to synthesize phytochelatins. However, the presence of a gene alone does not demonstrate that it plays a functional role in metal detoxification. In the present study, we show that the aquatic snail Lymnaea stagnalis produced both penta- and heptapeptide phytochelatins (i.e. phytochelatin-2 and phytochelatin-3), and their levels increased in response to sub-lethal levels of cadmium.

  18. "Rickettsia amblyommii" induces cross protection against lethal Rocky Mountain spotted fever in a guinea pig model.

    PubMed

    Blanton, Lucas S; Mendell, Nicole L; Walker, David H; Bouyer, Donald H

    2014-08-01

    Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia rickettsii for which there is no available vaccine. We hypothesize that exposure to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii" protects against R. rickettsii challenge. To test this hypothesis, guinea pigs were inoculated with "R. amblyommii." After inoculation, the animals showed no signs of illness. When later challenged with lethal doses of R. rickettsii, those previously exposed to "R. amblyommii" remained well, whereas unimmunized controls developed severe illness and died. We conclude that "R. amblyommii" induces an immune response that protects from illness and death in the guinea pig model of RMSF. These results provide a basis for exploring the use of low-virulence rickettsiae as a platform to develop live attenuated vaccine candidates to prevent severe rickettsioses.

  19. Sub-lethal cadmium exposure increases phytochelatin concentrations in the aquatic snail Lymnaea stagnalis.

    PubMed

    Sf, Gonçalves; Sk, Davies; Bennett, M; Raab, A; Feldmann, J; Kille, P; Loureiro, S; Dj, Spurgeon; Jg, Bundy

    2016-10-15

    Phytochelatins are metal-binding metabolites found in almost all plant species and some animal groups, including nematodes and annelids, where they can play an important role in detoxifying metals such as cadmium. Species from several other taxa contain a phytochelatin synthase (PCS) gene orthologue, including molluscs, indicating they may have the potential to synthesize phytochelatins. However, the presence of a gene alone does not demonstrate that it plays a functional role in metal detoxification. In the present study, we show that the aquatic snail Lymnaea stagnalis produced both penta- and heptapeptide phytochelatins (i.e. phytochelatin-2 and phytochelatin-3), and their levels increased in response to sub-lethal levels of cadmium. PMID:27358197

  20. Oxidative stress in hoof laminar tissue of horses with lethal gastrointestinal diseases.

    PubMed

    Laskoski, Luciane Maria; Dittrich, Rosangela Locatelli; Valadão, Carlos Augusto Araújo; Brum, Juliana Sperotto; Brandão, Yara; Brito, Harald Fernando Vicente; de Sousa, Renato Silva

    2016-03-01

    Tissue damage caused by oxidative stress is involved in the pathogenesis of several diseases in animals and man, and is believed to play a role in the development of laminitis in horses. The aim of this study was to investigate the oxidative stress associated with laminar lesions in horses with lethal gastrointestinal disorders. Laminar tissue samples of the hoof of 30 horses were used. Tissue samples were divided as follows: six healthy horses (control group-CG), and 24 horses that died after complications of gastrointestinal diseases (group suffering from gastrointestinal disorders-GDG). Superoxide dismutase (SOD2) and nitrotyrosine immunostaining and the severity of laminar lesions were evaluated. Presence of laminar lesions and immunostaining for nitrotyrosine and SOD2 were only evident in horses from the GDG group. Thus, oxidative stress may play a role in the pathogenesis of laminar lesions secondary to gastrointestinal disorders. PMID:26964719

  1. Cooperative study of clinical benefits from use of the fully portable blood irradiator

    SciTech Connect

    Hungate, F.P.

    1994-10-01

    This report looks at the clinical benefits from use of a fully portable blood irradiator, techniques developed by Pacific Northwest Laboratory. Significant accomplishments included the following: blood irradiators were successfully fabricated by PNL; irradiators were activated at the University of Missouri and quality tested at PNL; A-V shunts for irradiators were successfully fabricated in the PNL plastics shop; all activities necessary for experimental work on animals using the blood irradiators were completed.

  2. Potentiation of the anaphylatoxins in vivo using an inhibitor of serum carboxypeptidase N (SCPN). I. Lethality and pathologic effects on pulmonary tissue.

    PubMed Central

    Huey, R.; Bloor, C. M.; Kawahara, M. S.; Hugli, T. E.

    1983-01-01

    Carboxypeptidase N (EC 3.4.12.7) (SCPN) is a plasma enzyme that efficiently inactivates the anaphylatoxins C3a and C4a and significantly reduces C5a spasmogenic activity by removing the C-terminal arginyl residue from each of these factors. The arginine analog DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (SCPN-INH) is a potent competitive inhibitor of SCPN with a Ki for this carboxypeptidase in serum of 2 x 10(-9) M. Therefore, we have used the SCPN inhibitor to potentiate biologic activity of the anaphylatoxins in vivo. Infusion via the carotid artery of about 40 mg of SCPN-INH into each of 8 adult guinea pigs inactivated the SCPN for at least 3 hours and caused no measurable toxic effects. When cobra venom factor (CVF) is infused into guinea pigs, it activates the alternative pathway of complement, thereby generating the anaphylatoxins C3a and C5a. Ordinarily, infusion of CVF is nonlethal, because the generated anaphylatoxins are rapidly converted to C3a des Arg and C5a des Arg by SCPN. However, CVF (200 micrograms) plus SCPN-INH delivered intravenously in 5 animals induced a lethal reaction in less than 5 minutes. The authors conclude that the lethal effect is due largely to the anaphylatoxins. Histologic sections of the lungs from treated animals show dramatic structural changes consistent with peripheral small airway constriction, bronchial constriction, and vasoconstriction of small muscular arteries. Also, cell aggregates are present in blood vessels. Other histologic changes include severe congestion, pulmonary edema, and an interstitial infiltrate of mononuclear cells. Large doses of chlorpheniramine prevent this lethal reaction. Lethality is apparently attributable to asphyxia and is dependent on the level of CVF administered: eg, 100 micrograms CVF was not lethal in 4 animals given SCPN inhibitor, although signs of respiratory distress were observed. On histologic examination of lungs from guinea pigs given CVF and SCPN-INH, the features are

  3. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    PubMed

    Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

    2010-01-01

    The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  4. A Cysteine Protease Inhibitor Rescues Mice from a Lethal Cryptosporidium parvum Infection

    PubMed Central

    Nath-Chowdhury, Milli; Sajid, Mohammed; Marcus, Victoria; Mashiyama, Susan T.; Sakanari, Judy; Chow, Eric; Mackey, Zachary; Land, Kirkwood M.; Jacobson, Matthew P.; Kalyanaraman, Chakrapani; McKerrow, James H.; Arrowood, Michael J.; Caffrey, Conor R.

    2013-01-01

    Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, can stunt infant growth and can be lethal in immunocompromised individuals. The most widely used drugs for treating cryptosporidiosis are nitazoxanide and paromomycin, although both exhibit limited efficacy. To investigate an alternative approach to therapy, we demonstrate that the clan CA cysteine protease inhibitor N-methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K11777) inhibits C. parvum growth in mammalian cell lines in a concentration-dependent manner. Further, using the C57BL/6 gamma interferon receptor knockout (IFN-γR-KO) mouse model, which is highly susceptible to C. parvum, oral or intraperitoneal treatment with K11777 for 10 days rescued mice from otherwise lethal infections. Histologic examination of untreated mice showed intestinal inflammation, villous blunting, and abundant intracellular parasite stages. In contrast, K11777-treated mice (210 mg/kg of body weight/day) showed only minimal inflammation and no epithelial changes. Three putative protease targets (termed cryptopains 1 to 3, or CpaCATL-1, -2, and -3) were identified in the C. parvum genome, but only two are transcribed in infected mammals. A homology model predicted that K11777 would bind to cryptopain 1. Recombinant enzymatically active cryptopain 1 was successfully targeted by K11777 in a competition assay with a labeled active-site-directed probe. K11777 exhibited no toxicity in vitro and in vivo, and surviving animals remained free of parasites 3 weeks after treatment. The discovery that a cysteine protease inhibitor provides potent anticryptosporidial activity in an animal model of infection encourages the investigation and development of this biocide class as a new, and urgently needed, chemotherapy for cryptosporidiosis. PMID:24060869

  5. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    NASA Astrophysics Data System (ADS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  6. Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

    NASA Technical Reports Server (NTRS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2006-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  7. Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

    NASA Technical Reports Server (NTRS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2007-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  8. An ultrastructural analysis of the vascular damage in the lethal and sublethal Forssman reaction in the guinea-pig.

    PubMed Central

    Baker, J. R.; Bullock, G. R.; Butler, K. D.; Williamson, I. H.; White, A. M.

    1985-01-01

    The involvement of the complement system and platelets in the sublethal Forssman reaction in the guinea pig has been studied together with the ultrastructural changes observed in the endothelial cells of the pulmonary vasculature. The main ultrastructural change noted was swelling of the endothelium. This did not occur in thrombocytopenic animals or in decomplemented animals, indicating the importance of both platelets and the complement pathways in this reaction. The platelet inhibitors sulphinpyrazone or aspirin had no effect on endothelial swelling in the sublethal reaction. In the lethal reaction the degree of endothelial cell damage was more severe and included lesions in the cell membrane, lifting, necrosis and finally exposure of the basement membrane. This damage only occurred in animals with an intact complement cascade. Images Fig. 4 Fig. 5 Fig. 2 Fig. 3 Fig. 6 Fig. 7 PMID:3878720

  9. Animal picobirnavirus.

    PubMed

    Ganesh, Balasubramanian; Masachessi, Gisela; Mladenova, Zornitsa

    2014-01-01

    Picobirnavirus (PBV) is a small, non-enveloped, bisegmented double-stranded RNA (dsRNA) virus of vertebrate hosts. The name 'Picobirnavirus' derives from the prefix 'pico' (latin for 'small') in reference to the small virion size, plus the prefix 'bi' (latin for 'two') and the word 'RNA' to indicate the nature of the viral genome. The serendipitous discovery of PBV dates back to 1988 from Brazil, when human fecal samples collected during the acute gastroenteritis outbreaks were subjected for routine rotavirus surveillance by polyacrylamide gel electrophoresis (PAGE) and silver straining (S/S). The PAGE gels after silver staining showed a typical 'two RNA band' pattern, and it was identified as Picobirnavirus. Likewise, the feces of wild black-footed pigmy rice rats (Oryzomys nigripes) subjected for PAGE assay by the same research group in Brazil reported the presence of PBV (Pereira et al., J Gen Virol 69:2749-2754, 1988). PBVs have been detected in faeces of humans and wide range of animal species with or without diarrhoea, worldwide. The probable role of PBV as either a 'primary diarrhoeal agent' in 'immunocompetent children'; or a 'potential pathogen' in 'immunocompromised individuals' or an 'innocuous virus' in the intestine remains elusive and needs to be investigated despite the numerous reports of the presence of PBV in fecal samples of various species of domestic mammals, wild animals, birds and snakes; our current knowledge of their biology, etiology, pathogenicity or their transmission characteristics remains subtle. This review aims to analyse the veterinary and zoonotic aspects of animal Picobirnavirus infections since its discovery. PMID:25674589

  10. Animal behavior and animal welfare.

    PubMed

    Houpt, K A

    1991-04-15

    The value of behavioral techniques in assessing animal welfare, and in particular assessing the psychological well being of animals, is reviewed. Using cats and horses as examples, 3 behavioral methods are presented: (1) comparison of behavior patterns and time budgets; (2) choice tests; and (3) operant conditioning. The behaviors of intact and declawed cats were compared in order to determine if declawing led to behavioral problems or to a change in personality. Apparently it did not. The behavior of free ranging horses was compared with that of stabled horses. Using two-choice preference tests, the preference of horses for visual contact with other horses and the preference for bedding were determined. Horses show no significant preference for locations from which they can make visual contact with other horses, but they do prefer bedding, especially when lying down. Horses will perform an operant response in order to obtain light in a darkened barn or heat in an outside shed. These same techniques can be used to answer a variety of questions about an animal's motivation for a particular attribute of its environment. PMID:2061151

  11. Animal Testing

    NASA Astrophysics Data System (ADS)

    Moretto, Johnny; Chauffert, Bruno; Bouyer, Florence

    The development of a new anticancer drug is a long, complex and multistep process which is supervised by regulatory authorities from the different countries all around the world [1]. Application of a new drug for admission to the market is supported by preclinical and clinical data, both including the determination of pharmacodynamics, toxicity, antitumour activity, therapeutic index, etc. As preclinical studies are associated with high cost, optimization of animal experiments is crucial for the overall development of a new anticancer agent. Moreover, in vivo efficacy studies remain a determinant panel for advancement of agents to human trials and thus, require cautious design and interpretation from experimental and ethical point of views.

  12. Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model

    PubMed Central

    Pollpeter, Molly J.

    2016-01-01

    Background Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. Objective To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. Methods We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Results and Conclusions Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p < 0.0001). In addition, the hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated. PMID:27144769

  13. Median lethal concentration of formaldehyde and its genotoxic potential in bullfrog tadpoles (Lithobates catesbeianus).

    PubMed

    Santana, Juliana M; Dos Reis, Adriana; Teixeira, Patrícia C; Ferreira, Fábio C; Ferreira, Cláudia M

    2015-01-01

    In order to avoid that contaminated frog farms animals escaping in the environment and become potential vector of emergent diseases, studies with disinfection protocol are strictly necessary. The formaldehyde is one of the compounds tested in fungal disinfection protocols and also used in aquaculture. This study aimed to determine the median lethal concentration (LC50-96h) of formaldehyde in bullfrog tadpoles and to evaluate the possible genotoxic effects in acute exposition. Accordingly, the animals were exposed to formaldehyde in the concentrations of 6, 9, 12, 15, and 18 mg L(-1), and after 96 h blood samples were drawn for the micronucleus (MN) test. The LC50-96h was 10.53 mg L(-1), and the MN frequency increased in proportion to the formaldehyde concentrations, with an estimated frequency in the negative control being 1.35 MN/individual. We concluded that formaldehyde is genotoxic to tadpoles of bullfrogs in the tested concentrations, and the choice of this chemical should be contemplated before its use in animals in captivity.

  14. C. Elegans are Protected from Lethal Hypoxia by an Embryonic Diapause

    PubMed Central

    Miller, Dana L.; Roth, Mark B.

    2016-01-01

    Summary At least 100 mammalian species exhibit embryonic diapause, where fertilized embryos arrest development in utero until suitable seasonal or nutritional environments are encountered [1, 2]. Delaying maternal investments in producing offspring allows these animals to utilize limited resources to survive while searching for better conditions, and ensures that progeny are not produced when they are unlikely to survive. In addition, embryos may be protected from external environmental vicissitudes while in utero [3]. Here we demonstrate embryonic diapause in C. elegans, and show that this diapause protects embryos from otherwise lethal hypoxia. Diapausing embryos in utero require san-1 to survive, indicating that hypoxia-induced embryonic diapause may be mechanistically related to suspended animation. Furthermore, we show that neuronal HIF-1 activity in the adult dictates the O2 tension at which embryonic diapause is engaged. We suggest that the maternal perception of hypoxia stimulates a response to protect embryos in utero by inducing diapause, a natural form of suspended animation. This response is likely to be an important strategy to improve offspring survival in harsh conditions and allow adults to find environments more suitable for reproductive success. PMID:19576771

  15. Median lethal concentration of formaldehyde and its genotoxic potential in bullfrog tadpoles (Lithobates catesbeianus).

    PubMed

    Santana, Juliana M; Dos Reis, Adriana; Teixeira, Patrícia C; Ferreira, Fábio C; Ferreira, Cláudia M

    2015-01-01

    In order to avoid that contaminated frog farms animals escaping in the environment and become potential vector of emergent diseases, studies with disinfection protocol are strictly necessary. The formaldehyde is one of the compounds tested in fungal disinfection protocols and also used in aquaculture. This study aimed to determine the median lethal concentration (LC50-96h) of formaldehyde in bullfrog tadpoles and to evaluate the possible genotoxic effects in acute exposition. Accordingly, the animals were exposed to formaldehyde in the concentrations of 6, 9, 12, 15, and 18 mg L(-1), and after 96 h blood samples were drawn for the micronucleus (MN) test. The LC50-96h was 10.53 mg L(-1), and the MN frequency increased in proportion to the formaldehyde concentrations, with an estimated frequency in the negative control being 1.35 MN/individual. We concluded that formaldehyde is genotoxic to tadpoles of bullfrogs in the tested concentrations, and the choice of this chemical should be contemplated before its use in animals in captivity. PMID:26266476

  16. Tolazoline decreases survival time during microwave-induced lethal heat stress in anesthetized rats

    SciTech Connect

    Jauchem, J.R.; Chang, K.S.; Frei, M.R.

    1996-03-01

    Effects of {alpha}-adrenergic antagonists have been studied during environmental heating but not during microwave-induced heating. Tolazoline may exert some of its effects via {alpha}-adrenergic blockade. In the present study, ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/cm{sup 2} (whole-body specific absorption rate of approximately 14 W/kg) until lethal temperatures were attained. The effects of tolazoline (10 mg/kg body weight) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. Survival time was significantly shorter in the tolazoline group than in saline-treated animals. In general, heart rate and blood pressure responses were similar to those that occur during environmental heat stress. Heart rate, however, was significantly elevated in animals that received tolazoline, both before and during terminal microwave exposure. It is possible that changes associated with the elevated heart rate (e.g., less cardiac filling) in tolazoline-treated animals resulted in greater susceptibility to microwave-induced heating and the lower survival time. 47 refs., 3 figs., 2 tabs.

  17. Strategy for enhanced transgenic strain development for embryonic conditionnal lethality in Anastrepha suspensa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here the first reproductive sterility system for the tephritid pest, Anastrepha suspensa, is presented, based on lethality primarily in embryos heterozygous for a lethal conditional transgene combination. The tetracycline-suppressible system uses the cellularization-specific A. suspensa serendipity...

  18. Use of Irradiated Foods

    NASA Technical Reports Server (NTRS)

    Brynjolfsson, A.

    1985-01-01

    The safety of irradiated foods is reviewed. Guidelines and regulations for processing irradiated foods are considered. The radiolytic products formed in food when it is irradiated and its wholesomeness is discussed. It is concluded that food irradiation processing is not a panacea for all problems in food processing but when properly used will serve the space station well.

  19. Animal papillomaviruses.

    PubMed

    Rector, Annabel; Van Ranst, Marc

    2013-10-01

    We provide an overview of the host range, taxonomic classification and genomic diversity of animal papillomaviruses. The complete genomes of 112 non-human papillomavirus types, recovered from 54 different host species, are currently available in GenBank. The recent characterizations of reptilian papillomaviruses extend the host range of the Papillomaviridae to include all amniotes. Although the genetically diverse papillomaviruses have a highly conserved genomic lay-out, deviations from this prototypic genome organization are observed in several animal papillomaviruses, and only the core ORFs E1, E2, L2 and L1 are present in all characterized papillomavirus genomes. The discovery of papilloma-polyoma hybrids BPCV1 and BPCV2, containing a papillomaviral late region but an early region encoding typical polyomaviral nonstructural proteins, and the detection of recombination breakpoints between the early and late coding regions of cetacean papillomaviruses, could indicate that early and late gene cassettes of papillomaviruses are relatively independent entities that can be interchanged by recombination.

  20. ANIMAL COMMUNICATION.

    PubMed

    SEBEOK, T A

    1965-02-26

    Semiotics and ethology have converged in a new behavioral science, zoosemiotics. Those who are interested in the theoretical analysis of the complex problems of non-verbal behavior that arise where these two disciplines interact aim to treat comprehensively animal communication systems by the aid of representations that have proved illuminating in the study of sentences of human language. Students of zoosemiotics are concerned with codes and messages much as linguists are concerned with competence, or language, and performance, or speech. They thus face the twin tasks of constructing a model for the addresser to specify how a message is encoded and transformed into a signal carried by a variety of channels to the addressee; and of constructing a model for the addressee to specify the ways in which animals utilize their knowledge of their code to recognize the messages they receive. Finally, they assess the context of the communicative event in the hope of dissecting that which is relevant to the selection process from the rest of the background, a program for which there is as yet neither a procedural eliciting technique nor a satisfactory theoretical solution in sight.

  1. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli.

    PubMed

    Minnema, M C; Chang, A C; Jansen, P M; Lubbers, Y T; Pratt, B M; Whittaker, B G; Taylor, F B; Hack, C E; Friedman, B

    2000-02-15

    Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Escherichia coli infusion in baboons, but the mechanisms behind this effect are not clear. In the present study, we evaluated the effects of recombinant human ATIII (rhATIII) on the clinical course and the inflammatory cytokine and coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII starting 1 hour before an E coli challenge. Those in the control group were administered saline. Survival was significantly improved in the treatment group (P =.002). Both groups had similar hemodynamic responses to E coli challenge but different coagulation and inflammatory responses. The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls. In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons lethally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy. (Blood. 2000;95:1117-1123)

  2. Atropine sulfate and 2-pyridine aldoxime methylchloride elicit stress-induced convulsions and lethality in mice and guinea pigs.

    PubMed

    Donzanti, B A; Green, M D; Shores, E I

    1985-01-01

    The present study demonstrates that dose combinations of atropine sulfate and 2-pyridine aldoxime methylchloride (2-PAM), which do not produce any overt toxic effects on the behavior of mice or guinea pigs in a stable environment, elicit clonic-tonic convulsions and death when the animals are physically stressed by cold water swimming. Phenoxybenzamine (1-6 mg/kg), diazepam (0.625 and 1.25 mg/kg) and pilocarpine (2.5 and 5 mg/kg) significantly decreased (or abolished) the occurrence of atropine and 2-PAM stressed-induced convulsions and/or lethality. In contrast, propranolol (20 mg/kg), was ineffective in preventing either convulsions or lethality. Changes in plasma glucose levels and internal body temperature did not appear to explain the precipitation of convulsions or ensuing death. These results suggest that during acute physical stress, relatively low doses of atropine and 2-PAM produce toxic and lethal effects due to the activation of alpha-adrenergic mechanisms along with a concomitant inactivation of cholinergic mechanisms.

  3. Atropine sulfate and 2-pyridine aldoxime methylchloride elicit stress-induced convulsions and lethality in mice and guinea pigs.

    PubMed

    Donzanti, B A; Green, M D; Shores, E I

    1985-01-01

    The present study demonstrates that dose combinations of atropine sulfate and 2-pyridine aldoxime methylchloride (2-PAM), which do not produce any overt toxic effects on the behavior of mice or guinea pigs in a stable environment, elicit clonic-tonic convulsions and death when the animals are physically stressed by cold water swimming. Phenoxybenzamine (1-6 mg/kg), diazepam (0.625 and 1.25 mg/kg) and pilocarpine (2.5 and 5 mg/kg) significantly decreased (or abolished) the occurrence of atropine and 2-PAM stressed-induced convulsions and/or lethality. In contrast, propranolol (20 mg/kg), was ineffective in preventing either convulsions or lethality. Changes in plasma glucose levels and internal body temperature did not appear to explain the precipitation of convulsions or ensuing death. These results suggest that during acute physical stress, relatively low doses of atropine and 2-PAM produce toxic and lethal effects due to the activation of alpha-adrenergic mechanisms along with a concomitant inactivation of cholinergic mechanisms. PMID:4092617

  4. Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

    SciTech Connect

    Paessler, Slobodan Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

    2007-10-25

    We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta ({alpha}{beta}) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ({gamma}{delta}) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient ({mu}MT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3{sup +} T cells are required for protection.

  5. A framework for the assessment of non-lethal weapons.

    PubMed

    Rappert, Brian

    2004-01-01

    In many government, police and military circles, attention is being given to so-called 'non-lethal' weapons as means of reducing many of the negative effects directly or indirectly associated with the use of force. Despite the purported ability of the adoption of such weaponry to lessen grounds for contention and concern, past experience suggests the need for scepticism regarding the purported benefits. Rather than relying on poorly substantiated claims, comprehensive procedures are needed to ensure the appropriateness of force options. This article outlines some of the institutional structures required for 'carefully evaluating' and 'carefully controlling' non-lethal weapons, with a discussion of the perennial tensions associated with ensuring the relative 'acceptability' of the use of force. PMID:15015546

  6. Gene essentiality and synthetic lethality in haploid human cells.

    PubMed

    Blomen, Vincent A; Májek, Peter; Jae, Lucas T; Bigenzahn, Johannes W; Nieuwenhuis, Joppe; Staring, Jacqueline; Sacco, Roberto; van Diemen, Ferdy R; Olk, Nadine; Stukalov, Alexey; Marceau, Caleb; Janssen, Hans; Carette, Jan E; Bennett, Keiryn L; Colinge, Jacques; Superti-Furga, Giulio; Brummelkamp, Thijn R

    2015-11-27

    Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase β adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology. PMID:26472760

  7. Variability of platyspondylic lethal chondrodysplasia: another case report.

    PubMed

    Nishimura, G; Iwasawa, T; Fukuzawa, R; Hirabayashi, Y; Ito, T

    1998-07-01

    We report the radiological and histological findings of another case of platyspondylic lethal chondrodysplasia. The patient was a girl, who died of respiratory failure at 18 days of age. The radiological changes comprised moderate platyspondyly with ovoid-shaped vertebral bodies, broad and short ilia, rhizomelic shortening and mild bowing of the long bones (particularly of the humeri), relatively long short tubular bones, and retarded epiphyseal ossification and ragged metaphyses, which were most similar to those of a mild variant of this entity, the Luton type. However, the histological findings of cartilage, including hypercellularity of the reserve zone with round resting chondrocytes, relatively normal column formation of the proliferative and hypertrophic zones, and incorporation of hypertrophic cartilage with a columnar arrangement into metaphyseal bony trabeculae, resemble those of a severe variant of this entity, the Torrance type. Our observation provides an insight into the phenotypic variabilities of platyspondylic lethal chondrodysplasia. PMID:9689993

  8. Gene essentiality and synthetic lethality in haploid human cells.

    PubMed

    Blomen, Vincent A; Májek, Peter; Jae, Lucas T; Bigenzahn, Johannes W; Nieuwenhuis, Joppe; Staring, Jacqueline; Sacco, Roberto; van Diemen, Ferdy R; Olk, Nadine; Stukalov, Alexey; Marceau, Caleb; Janssen, Hans; Carette, Jan E; Bennett, Keiryn L; Colinge, Jacques; Superti-Furga, Giulio; Brummelkamp, Thijn R

    2015-11-27

    Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase β adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology.

  9. Medical ethics, cultural values, and physician participation in lethal injection.

    PubMed

    Boehnlein, J K; Parker, R M; Arnold, R M; Bosk, C F; Sparr, L F

    1995-01-01

    Capital punishment by lethal injection has been discussed in the literature, but there has been no consideration of the sociocultural foundations of the ethical issues related to medical aspects of capital punishment. Lethal injection represents the inappropriate medicalization of a complex social issue whereby medical skills and procedures are used in ways that contradict established medical practice. Although physicians are socialized to their healing role during medical education and training, their behavior is influenced by social and cultural values that both precede and coexist with their professional life. Because of this dynamic interplay between professional and sociocultural values, physicians can neither exempt themselves from societal debate by merely invoking professional ethics, nor can they define their professional role exclusively in terms of societal values that potentially diminish personal and collective professional responsibility. It is essential that physicians have a broad historical perspective on the development of the profession's standards and values in order to deal effectively with present and future complex ethical issues.

  10. Lethal congenital contracture syndrome: further delineation and genetic aspects.

    PubMed Central

    Vuopala, K; Herva, R

    1994-01-01

    In a national morphology based study of lethal arthrogryposis between 1979 and 1992, 40 fetuses and infants with lethal congenital contracture syndrome (LCCS, McKusick 253310) were found in Finland. The incidence of LCCS in Finland was 1:19,000 births. There were 20 affected males and 20 affected females in 26 families. In 16 cases the pregnancy was terminated after the prenatal diagnosis of total akinesia and fetal hydrops on ultrasound. There were 19 stillborn infants and five were born showing signs of life, but died within one hour. The segregation analyses yielded 0.45 affected by the "singles" method and 0.34 by the "sib" method. The birthplaces of the grandparents were located in the sparsely populated north east of Finland. This finding supports the existence of an autosomal recessive LCCS gene in Finland, particularly in the north eastern part. Images PMID:7966188

  11. Assessing lethal and sub-lethal effects of trichlorfon on different trophic levels.

    PubMed

    Coelho, Sónia; Oliveira, Rhaul; Pereira, Susana; Musso, Carolina; Domingues, Inês; Bhujel, Ram C; Soares, Amadeu M V M; Nogueira, António J A

    2011-06-01

    Trichlorfon (TCF) is one of the most used veterinary pharmaceuticals not only to fight infestations but also as a preventive measure worldwide. The high concentrations used generate concerns about environmental and human health. In this work we assessed the acute toxicity of this compound to non-target organisms belonging to different trophic levels: Danio rerio (early life stages and adults), Daphnia magna and algae (Pseudokirchneriella subcapitata and Chlorella vulgaris), and studied the potential of the biomarkers cholinesterase (ChE), glutathione-S-transferase (GST), lactate dehydrogenase (LDH) and catalase (CAT) to assess sub-lethal effects of trichlorfon in zebrafish and daphnids. The fish embryo test followed the OECD draft guideline FET and was based on the exposure of newly fertilized eggs to 0, 2.5, 5.0, 10, 20, 40, 80 and 160 mg/L of TCF for 5 days; the fish acute test followed the OECD guideline 203 and was based on the exposure of adult fish to 0, 2.5, 5, 10, 20, 40, 60 and 80 mg/L of TCF for 4 days; Daphnia sp. immobilization assay followed the OECD guideline 202 and was based on the exposure of juvenile daphnids to 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1 and 2 μg/L of TCF for 2 days and the algae growth inhibition assay followed the OECD guideline 201 and was based on the exposure of the two species to 0, 1, 3.2, 10, 32, 100 and 300 mg/L of TCF for 4 days. Biomarker levels were measured after 96 h exposure to TCF in zebrafish early life stages and adults and after 48 h exposure in D. magna. Tested organisms seem to have dissimilar sensitivities towards TCF exposure. D. magna (48 h-LC(50)=0.29 μg/L) was the most sensitive organism, followed by early life stages and adults of zebrafish (96 h-LC(50)=25.4 and 28.8 mg/L, respectively) and finally by the algae P. subcapitata (96 h-LC(50)=274.5 mg/L) and C. vulgaris (no effect observed). As daphnids are a source of food for organisms of higher trophic levels, the impairment on its population is prone to have

  12. Autopsy observations in lethal short-rib polydactyly syndromes.

    PubMed

    Okiro, Patricia; Wainwright, Helen; Spranger, Jürgen; Beighton, Peter

    2015-01-01

    The short rib-polydactyly syndromes are a heterogeneous group of lethal autosomal recessive disorders (SRP I-IV), which result from cellular ciliary dysfunction during embryogenesis. Diagnosis is conventionally based on radiographic imaging. Since 1976, postmortem investigations of 5 affected fetuses or stillbirths have been undertaken and the visceral abnormalities have been documented. These anomalies are discussed in the context of prenatal differential diagnosis and prognostication following imaging in pregnancy and at autopsy following miscarriage or stillbirth.

  13. Spondyloepiphyseal dysplasia congenita. A cause of lethal neonatal dwarfism.

    PubMed

    Macpherson, R I; Wood, B P

    1980-07-01

    Spondyloepiphyseal dysplasia congenita is a form of primary short dwarfism, that is manifest at birth generally has not been regarded as a cause of lethal neonatal dwarfism. Seven neonates with severe dwarfism are presented. The first survived the newborn period, but the other six were early neonatal deaths. All displayed the clinical and radiologic features of spondyloepiphyseal dysplasia congenita. The striking similarities between spondyloepiphyseal dysplasia congenita and achondrogenesis type 2 are discussed. PMID:6773018

  14. [Lethal achondrogenesis: a review of 56 cases (author's transl)].

    PubMed

    Schulte, M J; Lenz, W; Vogel, M

    1978-07-01

    54 cases with lethal achondrogenesis from the literature as well as two own cases are reviewed and analyzed with regard to the following characteristics: sex, hydramnios, breech presentation, duration of pregnancy, length and weight at birth, head circumference, length of upper and lower extremities, clinical and radiological data, age of mother and father at time of birth, familial occurrence and consanguinity of parents, histological, histochemical and electronmicroscopic tissue examination. PMID:353375

  15. Detection of irradiated liquor

    NASA Astrophysics Data System (ADS)

    Shengchu, Qi; Jilan, Wu; Rongyao, Yuan

    D-2,3-butanediol is formed by irradiation processes in irradiated liquors. This radiolytic product is not formed in unirradiated liquors and its presence can therefore be used to identify whether a liquor has been irradiated or not. The relation meso/dl≈1 for 2,3-butanediol and the amount present in irradiated liquors may therefore be used as an indication of the dose used in the irradiation.

  16. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  17. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  18. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  19. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  20. To Laugh in the Face of Death: The Games That Lethal People Play.

    ERIC Educational Resources Information Center

    Thorson, James A.; Powell, F. C.

    1990-01-01

    A total of 399 individuals completed a lethal behaviors scale and a measure of death anxiety, which were found to have no significant correlation. Predictors of lethalness included doing dangerous things for the fun of it and having ever driven a motorcycle. The most lethal individuals were young, male, and less educated. (Author/ABL)

  1. 28 CFR 552.25 - Use of chemical agents or non-lethal weapons.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Use of chemical agents or non-lethal weapons. 552.25 Section 552.25 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE... agents or non-lethal weapons. The Warden may authorize the use of chemical agents or non-lethal...

  2. Mouse model of sublethal and lethal intraperitoneal glanders (Burkholderia mallei).

    PubMed

    Fritz, D L; Vogel, P; Brown, D R; Deshazer, D; Waag, D M

    2000-11-01

    Sixty male BALB/c mice were inoculated intraperitoneally with either a sublethal or a lethal dose of Burkholderia mallei China 7 strain, then killed at multiple time points postinoculation. Histopathologic changes were qualitatively similar in both groups and consisted of pyogranulomatous inflammation. In sublethal study mice, changes were first seen at 6 hours in mediastinal lymph nodes, then in spleen, liver, peripheral lymph nodes, and bone marrow at day 3. These changes generally reached maximal incidence and severity by day 4 but decreased by comparison in all tissues except the liver. Changes were first seen in lethal study mice also at 6 hours in mediastinal lymph nodes and in spleens. At day 1, changes were present in liver, peripheral lymph nodes, and bone marrow. The incidence and severity of these changes were maximal at day 2. In contrast to sublethal study mice, the incidence and severity of the changes did not decrease through the remainder of the study. The most significant difference between the two groups was the rapid involvement of the spleen in the lethal study mice. Changes indicative of impaired vascular perfusion were more frequently seen in the sublethal study mice. Our findings indicate that mice are susceptible to B. mallei infection and may serve as an appropriate model for glanders infection in a resistant host such as human beings. Additionally, by immunoelectron microscopy, we showed the presence of type I O-antigenic polysaccharide (capsular) antigen surrounding B. mallei.

  3. Lethality of First Contact Dysentery Epidemics on Pacific Islands.

    PubMed

    Shanks, G Dennis

    2016-08-01

    Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. PMID:27185765

  4. Intact alternation performance in high lethality suicide attempters.

    PubMed

    Keilp, John G; Wyatt, Gwinne; Gorlyn, Marianne; Oquendo, Maria A; Burke, Ainsley K; John Mann, J

    2014-09-30

    Suicide attempters often perform poorly on tasks linked to ventral prefrontal cortical (VPFC) function. Object Alternation (OA) - a VPFC probe - has not been used in these studies. In this study, currently depressed medication-free past suicide attempters whose most severe attempt was of high (n=31) vs. low (n=64) lethality, 114 medication-free depressed non-attempters, and 86 non-patients completed a computerized OA task. Participants also completed comparison tasks assessing the discriminant validity of OA (Wisconsin Card Sort), its concurrent validity relative to tasks associated with past attempt status (computerized Stroop task, Buschke Selective Reminding Test), and its construct validity as a VPFC measure (Go-No Go and Iowa Gambling Task). Against expectations, high lethality suicide attempters - the majority of whom used non-violent methods in their attempts with some planning - outperformed other depressed groups on OA, with no group differences observed on Wisconsin Card Sort. Despite intact performance on OA, past attempters exhibited deficits on the Stroop and Buschke. OA performance was associated with performance on Go-No Go and Iowa Gambling, confirming that OA measures a similar construct. VPFC dysfunction may not be a characteristic of all suicide attempters, especially those who make more carefully planned, non-violent - though potentially lethal - attempts. PMID:24878299

  5. Structural basis for a lethal mutation in U6 RNA.

    PubMed

    Sashital, Dipali G; Allmann, Anne M; Van Doren, Steven R; Butcher, Samuel E

    2003-02-18

    U6 RNA is essential for nuclear pre-mRNA splicing and has been implicated directly in catalysis of intron removal. The U80G mutation at the essential magnesium binding site of the U6 3' intramolecular stem-loop region (ISL) is lethal in yeast. To further understand the structure and function of the U6 ISL, we have investigated the structural basis for the lethal U80G mutation by NMR and optical spectroscopy. The NMR structure reveals that the U80G mutation causes a structural rearrangement within the ISL resulting in the formation of a new Watson-Crick base pair (C67 x G80), and disrupts a protonated C67 x A79 wobble pair that forms in the wild-type structure. Despite the structural change, the accessibility of the metal binding site is unperturbed, and cadmium titration produces similar phosphorus chemical shift changes for both the U80G mutant and wild-type RNAs. The thermodynamic stability of the U80G mutant is significantly increased (Delta Delta G(fold) = -3.6 +/- 1.9 kcal/mol), consistent with formation of the Watson-Crick pair. Our structural and thermodynamic data, in combination with previous genetic data, suggest that the lethal basis for the U80G mutation is stem-loop hyperstabilization. This hyperstabilization may prevent the U6 ISL melting and rearrangement necessary for association with U4. PMID:12578359

  6. Crystallographic studies of the Anthrax lethal toxin. Annual report

    SciTech Connect

    Frederick, C.A.

    1996-07-01

    The lethal form of Anthrax results from the inhalation of anthrax spores. Death is primarily due to the effects of the lethal toxin (Protective Antigen (PA) + Lethal Factor) from the causative agent, Bacillus anthracis. All the Anthrax vaccines currently in use or under development contain or produce PA, the major antigenic component of anthrax toxin, and there is a clear need for an improved vaccine for human use. In the previous report we described the first atomic resolution structure of PA, revealing that the molecule is composed largely of beta-sheets organized into four domains. This information can be used in the design. of recombinant PA vaccines. In this report we describe additional features of the full-length PA molecule derived from further crystallographic refinement and careful examination of the structure. We compare two crystal forms of PA grown at different pH values and discuss the functional implications. A complete definition of the function of each domain must await the crystal structure of the PA63 heptamer. We have grown crystals of the heptamer under both detergent and detergent-free conditions, and made substantial progress towards the crystal structure. The mechanism of anthrax intoxication in the light of our results is reviewed.

  7. Lethal injection, autonomy and the proper ends of medicine.

    PubMed

    Silver, David

    2003-04-01

    Gerald Dworkin has argued that it is inconsistent with the proper ends of medicine for a physician to participate in an execution by lethal injection. He does this by proposing a principle by which we are to judge whether an action is consistent with the proper ends of medicine. I argue: (a) that this principle, if valid, does not show that it is inconsistent with the proper ends of medicine for a physician to participate in an execution by lethal injection; and (b) that this principle is not valid, and this is because it mistakenly views the promotion of patient autonomy as one of the proper ends of medicine. Rather, I propose, we should view respect for a patient's autonomy as a constraint on the pursuit of the proper ends of medicine, rather than as one of the proper ends itself. With this revised understanding of the proper ends of medicine, we can conclude that it is inconsistent with the proper ends of medicine for a physician to participate in an execution by lethal injection.

  8. Lethality of First Contact Dysentery Epidemics on Pacific Islands.

    PubMed

    Shanks, G Dennis

    2016-08-01

    Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history.

  9. RBE values and repair characteristics for colo-rectal injury after caesium 137 gamma-ray and neutron irradiation. II. Fractionation up to ten doses.

    PubMed

    Terry, N H; Denekamp, J

    1984-07-01

    Early and late colo-rectal damage in mice have been assessed after 137Cs gamma irradiation and 3 MeV neutrons given as 1,2,5 or 10 fractions. Damage was measured by early changes in body weight, the late production of short faecal pellets and the pattern of lethality after irradiation. The data have been analysed in terms of the time course of expression of damage, fractionation effects and the RBE for neutrons over a wide range of doses per fraction (0.5-12.5 Gy neutrons, 3.5-33.5 Gy gamma rays). An initial epithelial denudation led to an early loss of weight, maximal at 11-17 days after irradiation. A dose-dependent weight reduction persisted over the animals' life-time. Deaths after localised pelvic gamma irradiation were progressive with no sharp demarcation between early or late phases of injury. The time course for lethality was qualitatively similar after neutrons. Beyond six months the rectum became constricted by fibrosis and a higher proportion of small faecal pellets was observed. At 6-15 months relatively shallow dose-response curves were obtained for this change. The sparing effect of fractionation was marked for the gamma-irradiated mice and almost absent after neutrons. A very high repair increment (11 Gy) was seen with two gamma-ray fractions of 20 Gy. At lower doses per fraction the proportion of each gamma-ray fraction recovered was 50-69% for all assays, i.e., similar to that for other normal tissues. There was a slight enhancement in the sparing effect for the late compared with the early assays over the lower dose range. The RBE was strongly dependent on dose per fraction because of the lack of reparable damage after neutrons. The RBE for both early and late effects was 5.0 at a neutron dose per fraction of 1 Gy. Extrapolation of the RBE data to lower doses, using the linear quadratic model, predicts a higher RBE for late (7.4-12.7) than for early damage (5.7-8.5) if gamma-ray doses below 5 Gy are used.

  10. Effect of different laser irradiation on the dysentery bacilli

    NASA Astrophysics Data System (ADS)

    Ou, Lin; Chen, Rong; Chen, Yanjiao; Li, Depin; Wen, Caixia

    1998-08-01

    The S. flexnesi, which have high drug-resistance especially in Cm, Sm, Tc, SD, were irradiated by Ar+ laser at 488 nm and semiconductor laser at 808 nm. The experiment results have shown that both Ar+ laser and semiconductor laser with power density of 1.7 w/cm2 and irradiation dose of 2000 J/cm2 can conduce to the bacterial lethality and increase the mutation rates of the bacterial drug-sensitivity, and 'Colony Count' method have the superiority over the 'Inhibacteria Ring' method. At the mean time it further indicate that the high power semiconductor laser would play an important role in the sciences of laser biological medicine. But the effect of the near infrared semiconductor laser is far lower than that of Ar+ laser of shorter wavelength at the same irradiation dose. It is clear that the output and irradiation dose of near infrared semiconductor laser shall be increased in order to get the same rates of the bacterial lethality and the drug-sensitivity mutation as Ar+ laser's.

  11. Allograft tolerance in pigs after fractionated lymphoid irradiation. I. Skin grafts after partial lateral irradiation and bone marrow cell grafting

    SciTech Connect

    Vaiman, M.; Daburon, F.; Remy, J.; Villiers, P.A.; de Riberolles, C.; Lecompte, Y.; Mahouy, G.; Fradelizi, D.

    1981-05-01

    Experiments with pigs have been performed to establish bone marrow chimerism and skin graft tolerance between SLA genotyped animals. Recipients were conditioned by means of fractionated partial irradiation from lateral cobalt sources (partial lateral irradiation (PLI)). The head, neck, and lungs were protected with lead, the rest of the body being irradiated including the thymus, the majority of lymphoid organs with spleen, and most of the bone marrow sites.

  12. A scanning electron microscopic study of microvascular anastomoses on irradiated vessels: short-term effect of irradiation

    SciTech Connect

    De Wilde, R.; Boeckx, W.; Van Der Schueren, E.; Guelinckx, P.; Gruwez, J.

    1983-01-01

    Experiments were carried out to determine the effect of previous irradiation on microvascular arterial anastomoses. The study focused on regeneration of endothelial cells and thrombus formation. Careful examination with scanning electron microscopy (SEM) showed a difference between irradiated animals and a control group. In the irradiated group one can notice a decreased regeneration, a greater amount of fibrin and platelets, and a higher incidence of microthrombi.

  13. Irradiation of municipal sludge for agricultural use

    NASA Astrophysics Data System (ADS)

    Ahlstrom, Scott B.

    Research has demonstrated that irradiation is an effective means for reducing pathogens in sewage sludge to levels where sludge reuse in public areas meets criteria for protection of the public health. Complementary research has demonstrated the value of the irradiated sludge in both agronomic and animal science applications. The benefits of sludge application to cropland are well documented. The irradiation process does not increase the extractability and plant uptake of a broad range of nutrients and heavy metals from sludge-amended soils. However, it does eliminate the hazards associated with pathogen contamination when applying sludge to agricultural land. Irradiated sludge has also been evaluated as a supplemental foodstuff for cattle and sheep. The data indicate that products derived from raw sewage may have a substantial nutritive value for ruminant animals. Irradiation of sewage sludge is a practical means of sludge disinfection. Where a highly disinfected sludge is required, it should be considered as a viable sludge management alternative. Evaluation of sludge irradiation technology and its associated costs must be done with consideration of other sludge treatment processes to develop an acceptable sludge management system.

  14. Bioethical Problems: Animal Welfare, Animal Rights.

    ERIC Educational Resources Information Center

    March, B. E.

    1984-01-01

    Discusses various bioethical issues and problems related to animal welfare and animal rights. Areas examined include: Aristotelian views; animal welfare legislation; Darwin and evolutionary theory; animal and human behavior; and vegetarianism. A 14-point universal declaration of the rights of animals is included. (JN)

  15. Psychoactive-drug response is affected by acute low-level microwave irradiation

    SciTech Connect

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1983-01-01

    The effects of various psychoactive drugs were studied in rats exposed for 45 min in a circularly polarized, pulsed microwave field (2450 MHz; SAR 0.6 W/kg; 2-microseconds pulses, 500 pps). Apomorphine-induced hypothermia and stereotypy were enhanced by irradiation. Amphetamine-induced hyperthermia was attenuated while stereotypy was unaffected. Morphine-induced catalepsy and lethality were enhanced by irradiation at certain dosages of the drug. Since these drugs have different modes of action on central neural mechanisms and the effects of microwaves depend on the particular drug studied, these results show the complex nature of the effect of microwave irradiation on brain functions.

  16. Induction of transplantation tolerance in mice across major histocompatibility barrier by using allogeneic thymus transplantation and total lymphoid irradiation

    SciTech Connect

    Waer, M.; Palathumpat, V.; Sobis, H.; Vandeputte, M. )

    1990-07-15

    The use of allogeneic thymus transplantation as a means of inducing tolerance across MHC barriers was investigated in thymectomized, total lymphoid irradiated BALB/c mice. In 90% of the animals long term outgrowth of histologically normal C57BL thymus grafts was observed. None of the latter animals was chimeric. All thymus graft-bearing mice showed specific nonresponsiveness for C57BL MHC Ag in mixed lymphocyte reaction and cell-mediated lympholysis. Spleen cells of the C57BL thymus-bearing mice were unable to induce lethal graft-vs-host disease in neonatal (BALB/c X C57BL) F1 mice but provoked a vigorous graft-vs-host disease reaction in (BALB/c x C3H) F1 neonates. Tolerant mice permanently accepted C57BL heart and pancreas grafts, but all rejected C3H grafts. Induction of tolerance of BALB/c pre-T cells through allogeneic thymus graft and/or specific suppressor cells seems to be involved. The present model offers new opportunities to study thymocyte maturation in a fully allogeneic environment and may yield applications for clinical organ transplantation.

  17. Animal welfare: an animal science approach.

    PubMed

    Koknaroglu, H; Akunal, T

    2013-12-01

    Increasing world population and demand for animal-derived protein puts pressure on animal production to meet this demand. For this purpose animal breeding efforts were conducted to obtain the maximum yield that the genetic makeup of the animals permits. Under the influence of economics which is the driving force behind animal production, animal farming became more concentrated and controlled which resulted in rearing animals under confinement. Since more attention was given on economics and yield per animal, animal welfare and behavior were neglected. Animal welfare which can be defined as providing environmental conditions in which animals can display all their natural behaviors in nature started gaining importance in recent years. This does not necessarily mean that animals provided with good management practices would have better welfare conditions as some animals may be distressed even though they are in good environmental conditions. Consumers are willing to pay more for welfare-friendly products (e.g.: free range vs caged egg) and this will change the animal production practices in the future. Thus animal scientists will have to adapt themselves for the changing animal welfare rules and regulations that differ for farm animal species and countries. In this review paper, animal welfare is discussed from an animal science standpoint.

  18. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub

  19. Animating Brains

    PubMed Central

    Borck, Cornelius

    2016-01-01

    A recent paper famously accused the rising field of social neuroscience of using faulty statistics under the catchy title ‘Voodoo Correlations in Social Neuroscience’. This Special Issue invites us to take this claim as the starting point for a cross-cultural analysis: in which meaningful ways can recent research in the burgeoning field of functional imaging be described as, contrasted with, or simply compared to animistic practices? And what light does such a reading shed on the dynamics and effectiveness of a century of brain research into higher mental functions? Reviewing the heated debate from 2009 around recent trends in neuroimaging as a possible candidate for current instances of ‘soul catching’, the paper will then compare these forms of primarily image-based brain research with older regimes, revolving around the deciphering of the brain’s electrical activity. How has the move from a decoding paradigm to a representational regime affected the conceptualisation of self, psyche, mind and soul (if there still is such an entity)? And in what ways does modern technoscience provide new tools for animating brains? PMID:27292322

  20. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    PubMed

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p < 0.000. Bladder tumours accounts in CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

  1. Irradiation-related ischemic heart disease

    SciTech Connect

    Corn, B.W.; Trock, B.J.; Goodman, R.L. )

    1990-04-01

    An expectation for long-term survival has emerged among several groups of cancer patients treated with therapeutic irradiation (eg, Hodgkin's disease, early stage breast cancer). Therefore, the cardiovascular sequelae of thoracic irradiation have recently come under scrutiny. Animal models have demonstrated that cardiac irradiation can directly damage the myocardial microvasculature and can indirectly damage the coronary macrovasculature when coupled with cholesterol feeding. A clear association between thoracic radiotherapy and ischemic heart disease was observed among older clinical studies using radiotherapeutic techniques that are no longer optimal by today's standards. Such a relationship could not be confirmed in modern studies in which treatment factors (such as dose and volume of heart irradiated) were more carefully controlled. 56 references.

  2. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  3. DNA damage-processing in E. coli: on-going protein synthesis is required for fixation of UV-induced lethality and mutation.

    PubMed

    Burger, Amanda; Raymer, Jenny; Bockrath, R

    2002-10-01

    UV irradiation of E. coli produces photoproducts in the DNA genome. In consequence, some bacteria lose viability (colony-forming ability) or remain viable as mutant cells. However, the end-points of viability inactivation (lethality) or mutation are determined by cellular processes that act on the UV-damaged DNA. We have investigated the in vivo time course for processes that deal with cyclobutane pyrimidine dimers (CPD) which can be specifically removed by photoreactivation (PR). At different times during post-UV incubation, samples were challenged with PR and assayed for viability or mutation. We used excision-defective E. coli B/r cells and worked under yellow light to avoid background PR. During post-UV incubation (0-100min) in fully supplemented defined medium, inactivation and mutation were initially significantly reversed by PR but the extent of this reversal decreased during continued incubation defining "fixation" of lethality or mutation, respectively. In contrast, if protein synthesis was restricted during the post-UV incubation, no fixation developed. When chloramphenicol was added to inhibit protein synthesis after 30min of supplemented post-UV incubation, at a time sufficient for expression of UV-induced protein(s), fixation of lethality or mutation was still annulled (no change in the effectiveness of PR developed). Lethality fixation did progress when protein synthesis was restricted and the cells were incubated in the presence of puromycin or were either clpP or clpX defective. We discuss these and related results to suggest (1) on-going protein synthesis is required in the fixation process for lethality and mutation to sustain an effective level of a hypothetical protein sensitive to ClpXP proteolysis and (2) this protein plays a critical role in the process leading to exchange between Pol III activity and alternative polymerase activities required as each cell deals with damage in template DNA.

  4. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    SciTech Connect

    Sasaki, H.; Nishimoto, T. )

    1989-10-01

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD.

  5. Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation

    SciTech Connect

    Grosse, Nicole; Fontana, Andrea O.; Hug, Eugen B.; Lomax, Antony; Coray, Adolf; Augsburger, Marc; Paganetti, Harald; Sartori, Alessandro A.; Pruschy, Martin

    2014-01-01

    Purpose: To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation. Methods and Materials: The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining-deficient cells were analyzed after irradiation with clinically relevant, low-linear energy transfer (LET) protons and 200-keV photons. Results: All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR-deficient cells and wild-type cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual γH2AX foci after irradiation. Conclusion: Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways.

  6. Lethal and estrogenic effects of 4-nonylphenol in the cockle Cerastoderma glaucum.

    PubMed

    Marin, Maria Gabriella; Rigato, Stefano; Ricciardi, Francesco; Matozzo, Valerio

    2008-01-01

    The lethal and sublethal effects of the xenoestrogen 4-nonylphenol (NP) were evaluated in the cockle Cerastoderma glaucum. In a 96-h lethality test, bivalves were exposed to 0, 0+ acetone, 0.19, 0.38, 0.75, 1.5 and 3.0 mg NP/l. The 96-h LC(50) value was 0.3mg NP/l. No mortality was observed at 0.1 mg NP/l. The potential estrogenicity of NP was studied in both sexually undifferentiated (resting phase) and differentiated (pre-spawning phase) cockles, exposed for 7 and 14 days to 0, 0+ acetone, 0.0125, 0.025, 0.05, and 0.1 mg NP/l. Vitellogenin (Vg)-like protein levels were determined in both haemolymph and digestive gland by the alkali-labile phosphate (ALP) assay. In the resting phase, exposure for 7 days to 0.1 mg NP/l resulted in significant increases in ALP in both haemolymph and digestive gland, compared with controls. A significant increase was also observed in digestive gland of animals exposed to 0.0125 mg NP/l-exposed animals. After 14 days of exposure, haemolymph ALP levels were significantly increased in exposed animals at all NP concentrations tested, whereas no difference was recorded in digestive gland. In the pre-spawning phase, exposure for 7 days to NP significantly increased ALP levels in haemolymph from males exposed at all NP concentrations tested, whereas no significant variations were found in haemolymph from females. NP (0.05 and 0.1 mg/l) was also shown to increase ALP concentrations significantly in digestive gland of males, but not in those of females. Likewise, after 14 days' exposure, ALP levels significantly increased in haemolymph from males only at 0.1 mg NP/l. Conversely, NP caused significant increases in ALP levels in digestive gland from both males (at all NP concentrations tested) and females (at 0.025 and 0.1 mg NP/l). These results demonstrate that NP induces Vg synthesis in C. glaucum. Interestingly, males were more responsive to NP than females.

  7. A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge.

    PubMed

    Phoolcharoen, Waranyoo; Dye, John M; Kilbourne, Jacquelyn; Piensook, Khanrat; Pratt, William D; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S; Herbst-Kralovetz, Melissa M

    2011-12-20

    Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen-antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD(50) of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.

  8. Dominant lethal pathologies in male mice engineered to contain an X-linked DUX4 transgene

    PubMed Central

    Dandapat, Abhijit; Bosnakovski, Darko; Hartweck, Lynn M.; Arpke, Robert W.; Baltgalvis, Kristen A.; Vang, Derek; Baik, June; Darabi, Radbod; Perlingeiro, RitaC.R.; Hamra, F. Kent; Gupta, Kalpna; Lowe, Dawn A.; Kyba, Michael

    2014-01-01

    SUMMARY Facioscapulohumeral muscular dystrophy (FSHD) is an enigmatic disease associated with epigenetic alterations in the subtelomeric heterochromatin of the D4Z4 macrosatellite repeat. Each repeat unit encodes DUX4, a gene that is normally silent in most tissues. Besides muscular loss, most patients suffer retinal vascular telangiectasias. To generate an animal model, we introduced a doxycycline-inducible transgene encoding DUX4and 3′genomic DNA into a euchromatic region of the mouse X chromosome. Without induction, DUX4 RNA was expressed at low levels in many tissues and animals displayed a variety of unexpected dominant leaky phenotypes, including male-specific lethality. Remarkably, rare live-born males expressed DUX4 RNA in the retina and presented a retinal vascular telangiectasia. By using doxycycline to induce DUX4 expression in satellite cells, we observed impaired myogenesis in vitro and in vivo. This mouse model, which shows pathologies due to FSHD-related D4Z4 sequences, is likely to be useful for testing anti-DUX4 therapies in FSHD. PMID:25176645

  9. Preparation and characterization of cobalt-substituted anthrax lethal factor

    SciTech Connect

    Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.; Lo, Suet Y.; Siemann, Stefan

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressing Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.

  10. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    PubMed Central

    Hohmann, Miriam S. N.; Cardoso, Renato D. R.; Pinho-Ribeiro, Felipe A.; Crespigio, Jefferson; Cunha, Thiago M.; Alves-Filho, José C.; da Silva, Rosiane V.; Pinge-Filho, Phileno; Ferreira, Sergio H.; Cunha, Fernando Q.; Casagrande, Rubia; Verri, Waldiceu A.

    2013-01-01

    5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage. PMID:24288682

  11. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

    PubMed

    Safronetz, David; Rosenke, Kyle; Westover, Jonna B; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W; Feldmann, Heinz; Gowen, Brian B

    2015-01-01

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

  12. Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia

    PubMed Central

    Lindhurst, Marjorie J.; Fiermonte, Giuseppe; Song, Shiwei; Struys, Eduard; De Leonardis, Francesco; Schwartzberg, Pamela L.; Chen, Amy; Castegna, Alessandra; Verhoeven, Nanda; Mathews, Christopher K.; Palmieri, Ferdinando; Biesecker, Leslie G.

    2006-01-01

    SLC25A19 mutations cause Amish lethal microcephaly (MCPHA), which markedly retards brain development and leads to α-ketoglutaric aciduria. Previous data suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleotide transporter. We generated a knockout mouse model of Slc25a19. These animals had 100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day 10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a yolk sac erythropoietic failure, and elevated α-ketoglutarate in the amniotic fluid. We found that these animals have normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels, suggesting that transport of these molecules is not the primary role of SLC25A19. We identified thiamine pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through homology searching and confirmed it by using transport assays of the recombinant reconstituted protein. The mitochondria of Slc25a19−/− and MCPHA cells have undetectable and markedly reduced ThPP content, respectively. The reduction of ThPP levels causes dysfunction of the α-ketoglutarate dehydrogenase complex, which explains the high levels of this organic acid in MCPHA and suggests that mitochondrial ThPP transport is important for CNS development. PMID:17035501

  13. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

    PubMed

    Safronetz, David; Rosenke, Kyle; Westover, Jonna B; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W; Feldmann, Heinz; Gowen, Brian B

    2015-01-01

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs. PMID:26456301

  14. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

    PubMed Central

    Safronetz, David; Rosenke, Kyle; Westover, Jonna B.; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W.; Feldmann, Heinz; Gowen, Brian B.

    2015-01-01

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs. PMID:26456301

  15. Perinatal lethal type II osteogenesis imperfecta: a case report

    PubMed Central

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure. PMID:26401205

  16. Intimate partner homicide: new insights for understanding lethality and risks.

    PubMed

    Sheehan, Brynn E; Murphy, Sharon B; Moynihan, Mary M; Dudley-Fennessey, Erin; Stapleton, Jane G

    2015-02-01

    Research on covictims, family members, and close friends who have lost loved ones to intimate partner homicide (IPH) is a neglected area of study. We conducted phenomenological interviews with covictims to gain insights into risk and lethality, examined affidavits from criminal case files, and reviewed news releases. The data uncovered acute risk factors prior to the homicide, identified changes in the perpetrators' behavior and the perpetrators' perceived loss of control over the victim, and described barriers that victims faced when attempting to gain safety. Findings suggest that recognizing acute risk factors is an important area for future IPH research.

  17. Potent inhibitors of anthrax lethal factor from green tea

    PubMed Central

    Dell'Aica, Isabella; Donà, Massimo; Tonello, Fiorella; Piris, Alejandro; Mock, Michèle; Montecucco, Cesare; Garbisa, Spiridione

    2004-01-01

    The anthrax lethal factor (LF) has a major role in the development of anthrax. LF is delivered by the protective antigen (PA) inside the cell, where it exerts its metalloprotease activity on the N-terminus of MAPK-kinases. PA+LF are cytotoxic to macrophages in culture and kill the Fischer 344 rat when injected intravenously. We describe here the properties of some polyphenols contained in green tea as powerful inhibitors of LF metalloproteolytic activity, and how the main catechin of green tea, (−)epigallocatechin-3-gallate, prevents the LF-induced death of macrophages and Fischer 344 rats. PMID:15031715

  18. Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity.

    PubMed

    Malik, Sushma; Paldiwal, Ashutosh Abhimanyu; Korday, Charusheela Sujit; Jadhav, Shruti Sudhir

    2015-10-01

    Carnitine palmitoyltransferase II (CPTII) deficiency is a rare disorder of mitochondrial fatty acid oxidation with autosomal recessive mode of inheritance. Three classic forms of CPT II deficiency have been described namely the lethal neonatal form, severe infantile hepatocardiomuscular form and the myopathic form. We present a three-day-old female child, admitted to us for lethargy, icterus, low sugars and convulsions. Persistent non ketotic hypoglycaemia, hyperammonemia, raised liver enzymes with hepatomegaly and cardiomyopathy led to the suspicion of fatty acid oxidation defect. Tandem mass spectrometry helped to clinch the diagnosis of CPT II Deficiency in the present case. PMID:26557586

  19. Commercial food irradiation

    SciTech Connect

    Black, E.F.; Libby, L.M.

    1983-06-01

    Food irradiation is discussed. Irradiation exposes food to gamma rays from a cobalt-60 or a cesium-137 source, or to high-energy electrons emitted by an electron accelerator. A major advantage is that food can be packaged either before or after treatment. FDA regulations with regard to irradiation are discussed. Comments on an 'Advance Notice' on irradiation, published by the FDA in 1981 are summarized.

  20. Effect of preoperative irradiation on healing of low colorectal anastomoses

    SciTech Connect

    Morgenstern, L.; Sanders, G.; Wahlstrom, E.; Yadegar, J.; Amodeo, P.

    1984-02-01

    The effect of preoperative irradiation on the healing of low colorectal anastomoses was studied experimentally. In 12 dogs in whom preoperative irradiation of 4,000 rads was given before low colorectal stapled anastomosis was performed, anastomotic leakage occurred in 66 percent. More than half of the anastomotic leaks were associated with either severe sepsis or death. In a matched group of control animals that underwent stapled anastomoses without irradiation, no anastomotic complications occurred. The clinical implications of this study are that stapled anastomoses in irradiated colon are at serious risk of anastomotic dehiscence and, therefore, should be protected with a proximal colostomy.

  1. Consumer in-store response to irradiated papayas

    SciTech Connect

    Bruhn, C.M.; Noell, J.W.

    1987-09-01

    In this study, purchase behavior of California consumers in response to irradiated papayas is described. The papayas were shipped from Hawaii and irradiated in California under a permit by the Animal and Plant Health Inspection Service and approved by the California Department of Food and Agriculture. Results show that the superior appearance of the irradiated fruit appealed to consumers and that two-thirds or more of the people queried indicated that they would buy irradiated produce. It is noted that this marketing took place in a supportive environment with no protestors present. Informational material was available.

  2. Lethal and sub-lethal effects of elevated CO2 concentrations on marine benthic invertebrates and fish.

    PubMed

    Lee, Changkeun; Hong, Seongjin; Kwon, Bong-Oh; Lee, Jung-Ho; Ryu, Jongseong; Park, Young-Gyu; Kang, Seong-Gil; Khim, Jong Seong

    2016-08-01

    Concern about leakage of carbon dioxide (CO2) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO2 affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO2, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO2, with the Venus clam being the most tolerant (LpH50 = 5.45). Sub-tidal species (such as brittle starfish [LpH50 = 6.16] and marine medaka [LpH50 = 5.91]) were more sensitive to elevated CO2 compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO2. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO2 and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO2 adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO2.

  3. Lethal and sub-lethal effects of elevated CO2 concentrations on marine benthic invertebrates and fish.

    PubMed

    Lee, Changkeun; Hong, Seongjin; Kwon, Bong-Oh; Lee, Jung-Ho; Ryu, Jongseong; Park, Young-Gyu; Kang, Seong-Gil; Khim, Jong Seong

    2016-08-01

    Concern about leakage of carbon dioxide (CO2) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO2 affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO2, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO2, with the Venus clam being the most tolerant (LpH50 = 5.45). Sub-tidal species (such as brittle starfish [LpH50 = 6.16] and marine medaka [LpH50 = 5.91]) were more sensitive to elevated CO2 compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO2. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO2 and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO2 adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO2. PMID:27074931

  4. [Analysis of recessive sex-linked lethal mutations in genotypically different strains of Drosophila melanogaster MS and w, exposed in the 5-kilometer zone of the accident at the Chernobyl nuclear reactor].

    PubMed

    Aslanian, M M; Kim, A I; Magomedova, M A; Fatkulbaianova, N L

    1994-09-01

    The frequency of induced and spontaneous recessive sex-linked lethal mutations (RSLLM) in Drosophila melanogaster strains w and ms was estimated after their chronic irradiation in the five-kilometer zone of the Chernobyl' meltdown. The mutagenic effect of relatively low radiation doses was analyzed. In an experiment conducted in 1990, a significant increase in the RSLLM frequency was recorded, while, in 1991, no significant difference between the experiment and control was found.

  5. Lethal body burdens of polar narcotic chemicals: Chlorophenols

    SciTech Connect

    Wezel, A. van; Punte, S.; Opperhuizen, A.

    1994-12-31

    Lethal body burdens (LBBs) were measured of low chlorinated phenols to obtain insight in the intrinsic toxicity of these compounds and in the origins of differences in toxicity between polar and nonpolar narcotic chemicals. Fathead minnows were exposed until death to 2-chlorophenol, 4-chlorophenol or 2,4-chlorophenol at fixed pH. LBBs of chlorophenols were shown to be significantly lower than LBBs of the nonpolar chlorobenzenes. The pH of the exposure doesn`t influence the LBB of chlorophenols, whereas it does influence chemical speciation and thus the uptake and the LC50 of the chlorophenols. Octanol-water partition coefficients were measured at different pH, to gain insight in the distribution of the chlorophenols between aqueous and fatty compartments inside the organism. It is shown that at a physiological pH only a fraction of the total amount of chlorophenols inside the organism is accumulated in the fatty parts of the organism. These fatty parts, including the membranes, are usually considered as the target site for narcotic chemicals. It is concluded that the concentration at the membrane needed for lethality is lower for polar narcotic chemicals than for nonpolar narcotic chemicals, implying either a different mode of action at the same target site or another target site.

  6. Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir

    PubMed Central

    de Ávila, Ana I.; Gallego, Isabel; Soria, Maria Eugenia; Gregori, Josep; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.; Domingo, Esteban; Perales, Celia

    2016-01-01

    Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagen. Here we show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during its replication in human hepatoma cells. T-705 leads to an excess of G → A and C → U transitions in the mutant spectrum of preextinction HCV populations. Infectivity decreased significantly in the presence of concentrations of T-705 which are 2- to 8-fold lower than its cytotoxic concentration 50 (CC50). Passaging the virus five times in the presence of 400 μM T-705 resulted in virus extinction. Since T-705 has undergone advanced clinical trials for approval for human use, the results open a new approach based on lethal mutagenesis to treat hepatitis C virus infections. If proven effective for HCV in vivo, this new anti-HCV agent may be useful in patient groups that fail current therapeutic regimens. PMID:27755573

  7. Molecular markers in prostate cancer. Part I: predicting lethality

    PubMed Central

    Agrawal, Sachin; Dunsmuir, William D.

    2009-01-01

    Assessing the lethality of 'early,' potentially organ-confined prostate cancer (PCa) is one of the central controversies in modern-day urological clinical practice. Such cases are often considered for radical 'curative' treatment, although active surveillance may be equally appropriate for many men. Moreover, the balance between judicious intervention and overtreatment can be difficult to judge. The patient's age, comorbidities, family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease, the number and percentage of biopsy cores involved with the disease, histological grade, presenting prostate-specific antigen (PSA) and possible previous PSA kinetics. For many years, scientists and physicians have sought additional molecular factors that may be predictive for disease stage, progression and lethality. Usually, claims for a 'new' unique marker fall short of true clinical value. More often than not, such molecular markers are useful only in multivariate models. This review summarizes relevant molecular markers and models reported up to and including 2008. PMID:19050690

  8. Equation of state and fragmentation issues in computational lethality analysis

    SciTech Connect

    Trucano, T.G.

    1993-07-01

    The purpose of this report is to summarize the status of computational analysis of hypervelocity impact lethality in relatively nontechnical terms from the perspective of the author. It is not intended to be a review of the technical literature on the problems of concern. The discussion is focused by concentrating on two phenomenology areas which are of particular concern in computational impact studies. First, the material`s equation of state, specifically the treatment of expanded states of metals undergoing shock vaporization, is discussed. Second, the process of dynamic fragmentation is addressed. In both cases, the context of the discussion deals with inaccuracies and difficulties associated with numerical hypervelocity impact simulations. Laboratory experimental capabilities in hypervelocity impact for impact velocities greater than 10.0 km/s are becoming increasingly viable. This paper also gives recommendations for experimental thrusts which utilize these capabilities that will help to resolve the uncertainties in the numerical lethality studies that are pointed out in the present report.

  9. Effectiveness of lethal, directed wolf-depredation control in Minnesota

    USGS Publications Warehouse

    Harper, E.K.; Paul, W.J.; Mech, L.D.; Weisberg, S.

    2008-01-01

    Wolf (Canis lupus) depredations on livestock in Minnesota, USA, are an economic problem for many livestock producers, and depredating wolves are lethally controlled. We sought to determine the effectiveness of lethal control through the analysis of data from 923 government-verified wolf depredations from 1979 to 1998. We analyzed the data by 1) assessing the correlations between the number of wolves killed in response to depredations with number of depredations the following year at state and local levels, and 2) the time to the next depredation. No analysis indicated that trapping wolves substantially reduced the following year's depredations at state or local levels. However, more specific analyses indicated that in certain situations, killing wolves was more effective than no action (i.e., not trapping). For example, trapping and killing adult males decreased the re-depredation risk. At sheep farms, killing wolves was generally effective. Attempting to trap, regardless of the results, seemed more effective at reducing depredations than not trapping, suggesting that mere human activity near depredation sites might deter future depredations.

  10. Fluorescence resonance energy transfer studies on anthrax lethal toxin.

    PubMed

    Croney, John C; Cunningham, Kristina M; Collier, R John; Jameson, David M

    2003-08-28

    Anthrax lethal toxin is a binary bacterial toxin consisting of two proteins, protective antigen (PA) and lethal factor (LF), that self-assemble on receptor-bearing eukaryotic cells to form toxic, non-covalent complexes. PA(63), a proteolytically activated form of PA, spontaneously oligomerizes to form ring-shaped heptamers that bind LF and translocate it into the cell. Site-directed mutagenesis was used to substitute cysteine for each of three residues (N209, E614 and E733) at various levels on the lateral face of the PA(63) heptamer and for one residue (E126) on LF(N), the 30 kDa N-terminal PA binding domain of LF. Cysteine residues in PA were labeled with IAEDANS and that in LF(N) was labeled with Alexa 488 maleimide. The mutagenesis and labeling did not significantly affect function. Time-resolved fluorescence methods were used to study fluorescence resonance energy transfer (FRET) between the AEDANS and Alexa 488 probes after the complex assembled in solution. The results clearly indicate energy transfer between AEDANS labeled at residue N209C on PA and the Alexa 488-labeled LF(N), whereas transfer from residue E614C on PA was slight, and none was observed from residue E733C. These results support a model in which LF(N) binds near the top of the ring-shaped (PA(63))(7) heptamer.

  11. Injury risk assessment of non-lethal projectile head impacts.

    PubMed

    Oukara, Amar; Nsiampa, Nestor; Robbe, Cyril; Papy, Alexandre

    2014-01-01

    Kinetic energy non-lethal projectiles are used to impart sufficient effect onto a person in order to deter uncivil or hazardous behavior with a low probability of permanent injury. Since their first use, real cases indicate that the injuries inflicted by such projectiles may be irreversible and sometimes lead to death, especially for the head impacts. Given the high velocities and the low masses involved in such impacts, the assessment approaches proposed in automotive crash tests and sports may not be appropriate. Therefore, there is a need of a specific approach to assess the lethality of these projectiles. In this framework, some recent research data referred in this article as "force wall approach" suggest the use of three lesional thresholds (unconsciousness, meningeal damages and bone damages) that depend on the intracranial pressure. Three corresponding critical impact forces are determined for a reference projectile. Based on the principle that equal rigid wall maximal impact forces will produce equal damage on the head, these limits can be determined for any other projectile. In order to validate the consistence of this innovative method, it is necessary to compare the results with other existing assessment methods. This paper proposes a comparison between the "force wall approach" and two different head models. The first one is a numerical model (Strasbourg University Finite Element Head Model-SUFEHM) from Strasbourg University; the second one is a mechanical surrogate (Ballistics Load Sensing Headform-BLSH) from Biokinetics. PMID:25400712

  12. The lethal effects of Cyperus iria on Aedes aegypti.

    PubMed

    Schwartz, A M; Paskewitz, S M; Orth, A P; Tesch, M J; Toong, Y C; Goodman, W G

    1998-03-01

    The sedge Cyperus iria, a common weed in rice, contains large amounts of the insect hormone (10R) juvenile hormone III (JH III). Given its widespread distribution in Asia and Africa, we examined the possibility that C. iria could be used as a safe, inexpensive, and readily available mosquito larvicide. Plants of varying ages were harvested and leaves tested for lethal effects on larvae of the yellow fever mosquito, Aedes aegypti. The median lethal doses (LD50s) for frozen leaves from 1- and 2-month-old plants were 267 and 427 mg/100 ml of water, respectively. Leaves from 1-month-old C. iria contained 193 micrograms JH III/g fresh weight, whereas leaves from 2-month-old plants contained 143 micrograms JH III/g fresh weight. Larval sensitivity to the plant differed with age; 4-day-old larvae displayed the greatest mortality followed in decreasing sensitivity by larvae 5, 6, 3, and 2 days old. Six Cyperus species (C. albostriatus, C. alternifolius, C. esculentus, C. iria, C. miliifolius, and C. papyrus) of similar developmental stage were assayed for JH III content. Only C. iria was found to contain significant levels of JH III. PMID:9599328

  13. Non-lethal sampling for mercury evaluation in crocodilians.

    PubMed

    Lázaro, Wilkinson L; de Oliveira, Robson F; dos Santos-Filho, Manoel; da Silva, Carolina J; Malm, Olaf; Ignácio, Áurea R A; Díez, Sergi

    2015-11-01

    Mercury (Hg) is a ubiquitous environmental contaminant that poses potential threats to ecosystems due to its toxicity to humans and wildlife. The development of non-lethal sampling techniques is a critical step for evaluation of Hg in threatened species in tropical floodplain environments, where most of Hg found is the result of land use and gold mining activities, and more methylation sites are available. We evaluated the spatial and seasonal effectiveness of caudal scutes and claws to estimate Hg bioaccumulation in crocodilians (Caiman yacare), in the scarcely documented Pantanal. Hence, we investigated the potential for Hg bioaccumulation in top predators according to its proximity to mining sites, and in water bodies with different hydrological characteristics and connectivity with the main river during two phases of the flood pulse (dry and flood). The highest Hg concentrations were detected in caimans captured close to mining activities, in claws (2176 ng g(-1) ww) and caudal scutes (388 ng g(-1) ww). THg concentration in claws was related to the flood season and its mean concentration was thirteen fold higher than Hg concentration in scutes during whole year. Both tissues were found to be effective as non-lethal sampling techniques for measuring Hg bioaccumulation in reptiles over time. Nevertheless, claw tissue seems to have a more consistent result, since its constitutional chemical characteristics makes it a better indicator of spatial patterns that influence on Hg exposure. PMID:26026900

  14. Lethal Nipah virus infection induces rapid overexpression of CXCL10.

    PubMed

    Mathieu, Cyrille; Guillaume, Vanessa; Sabine, Amélie; Ong, Kien Chai; Wong, Kum Thong; Legras-Lachuer, Catherine; Horvat, Branka

    2012-01-01

    Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

  15. Injury Risk Assessment of Non-Lethal Projectile Head Impacts

    PubMed Central

    Oukara, Amar; Nsiampa, Nestor; Robbe, Cyril; Papy, Alexandre

    2014-01-01

    Kinetic energy non-lethal projectiles are used to impart sufficient effect onto a person in order to deter uncivil or hazardous behavior with a low probability of permanent injury. Since their first use, real cases indicate that the injuries inflicted by such projectiles may be irreversible and sometimes lead to death, especially for the head impacts. Given the high velocities and the low masses involved in such impacts, the assessment approaches proposed in automotive crash tests and sports may not be appropriate. Therefore, there is a need of a specific approach to assess the lethality of these projectiles. In this framework, some recent research data referred in this article as “force wall approach” suggest the use of three lesional thresholds (unconsciousness, meningeal damages and bone damages) that depend on the intracranial pressure. Three corresponding critical impact forces are determined for a reference projectile. Based on the principle that equal rigid wall maximal impact forces will produce equal damage on the head, these limits can be determined for any other projectile. In order to validate the consistence of this innovative method, it is necessary to compare the results with other existing assessment methods. This paper proposes a comparison between the “force wall approach” and two different head models. The first one is a numerical model (Strasbourg University Finite Element Head Model-SUFEHM) from Strasbourg University; the second one is a mechanical surrogate (Ballistics Load Sensing Headform-BLSH) from Biokinetics. PMID:25400712

  16. Influences of Microwave Irradiation on Environment

    NASA Astrophysics Data System (ADS)

    Murakami, H.; Abe, Y.; Iwata, T.; Kudo, I.; Saito, K.; Okuda, T.

    2004-12-01

    An experimental facility to evaluate the long-duration influence of microwave to environment, a so-called long duration microwave exposure facility (LDMEF), was constructed in Tsukuba in 1994, and so far irradiation tests on plants accumulated over 40,000 hours have been conducted with the aid of 2.45 GHz magnetron. The LDMEF consists of a pair of outdoor electromagnetically isolated areas, one under the influence of microwave irradiation with a 500 W magnetron and one without microwave irradiation. The growth rates of plants in both areas were compared and evaluated with the experimental data for the temperature distribution in the soil and power distribution of microwave. Although any appreciable influence of microwave was not noticed in the power density less than 10 mW/cm2 , the experimental results showed a significant growth rate enhancement when the power density became over 10 mW/cm2 . However, the growth was rather depressed when the power density increased over 15 mW/cm2 . These effects are well explained by the temperature and moisture in the soil which are also under an appreciable influence of microwave irradiation [1,2]. In this context, we newly constructed an indoor irradiation facility, in which the growth conditions of plants under a constant soil temperature can be maintained. In addition, irradiation with a 5.8 GHz magnetron will be conducted in the new facility. In parallel to a series of indoor and outdoor irradiation tests on plants, the influence of microwave irradiation on the growth pattern of albino mouse will be conducted. This experiment will be the first experimental evaluation for the influence of microwave irradiation on animals.

  17. Controlling periodontal bone levels with multiple LED irradiations.

    PubMed

    Chang, Po-Chun; Wang, Chen-Ying; Chong, Li Yen

    2015-02-01

    Because a single exposure to light-emitting diode (LED) irradiation at 660 nm only demonstrated a 3-day biostimulatory effect in recovering periodontal bone level (PBL), this study sought to evaluate whether the periodontal effect could be extended through the use of multiple LED irradiations. Experimental periodontitis was developed unilaterally in 48 Sprague-Dawley rats after the placement of a silk ligature plus Porphyromonas gingivalis lipopolysaccharide injections. The animals were divided into four groups (no irradiation, a single irradiation, or two or three irradiations per week) and exposed to LED light irradiation at a wavelength of 660 ± 25 nm and energy density of 10 J/cm(2) after debridement and detoxification. The animals were euthanized after 7 or 14 days, and the effect of irradiation was evaluated using micro-computed tomography and histology. By day 7, PBL was significantly reduced (p < 0.05), with significantly reduced inflammation (p < 0.05) and gingival hyperplasia (p < 0.001), in the animals receiving three irradiations per week. At day 14, the reduction in gingival hyperplasia was still significant (p < 0.05), and collagen matrix deposition and realignment appeared to be accelerated in the animals receiving three irradiations per week, despite a lack of significant difference in PBL. The treatment regimen receiving three LED light irradiations per week apparently extended the effects in reducing PBL and inflammation to 7 days. The inclusion of additional inflammation control measures or the addition of bioactive signals to mediate the repairing process is necessary to maintain long-term periodontal stability.

  18. Programs in Animal Agriculture.

    ERIC Educational Resources Information Center

    Herring, Don R.; And Others

    1980-01-01

    Five topics relating to programs in animal agriculture are addressed: (1) the future of animal agriculture; (2) preparing teachers in animal agriculture; (3) how animal programs help young people; (4) a nontraditional animal agriculture program; and (5) developing competencies in animal agriculture. (LRA)

  19. Methods for routine control of irradiated food: Determination of the irradiation status of shellfish by thermoluminescence analysis

    NASA Astrophysics Data System (ADS)

    Schreiber, G. A.; Hoffmann, A.; Helle, N.; Bögl, K. W.

    1994-06-01

    In some countries, clearance has been given for treating certain types of shellfish by ionizing radiation in order to increase the shelf-life and to reduce health hazards which might be caused by contaminating microorganisms. In the present study, thermoluminescence (TL) analysis was used to examine the irradiation status of shellfish products purchased from local suppliers. For analysis minerals were isolated from the guts of the animals. Although on none of the examined products an irradiation treatment prior to analysis could be shown, the results obtained on non-irradiated and irradiated products have revealed that irradiation within the commercially used dose range can clearly be detected. Already first glow TL intensities of minerald indicated irradiation treatments. Normalized TL signals of non-irradiated and irradiated samples were clearly separated. By calculation of differences of TL intensities and TL signals between non-irradiated and irradiated samples in dependency of integration temperature an optimized integration area for glow curves was determined. The result of this study agree well with results obtained by two large-scale intercomparisons between food control laboratories to detect irradiation treatment of spices and herbal products as well as of fruit and vegetables by TL analysis of contaminating minerals.

  20. Antibody-dependent cellular cytotoxicity-mediated serotherapy against murine neuroblastoma. II. In vitro and in vivo treatment using effector cells from normal and X-irradiated humans.

    PubMed

    Byfield, J E; Zerubavel, R; Fonkalsrud, E W

    1983-01-01

    Human peripheral lymphocytes (HLc) have been studied in vitro as possible effector cells in an antibody-dependent cellular cytotoxicity (ADCC) reaction. HLc were found to be active against murine neuroblastoma cells (MNB) inoculated into the flank of syngeneic mice. Both the time of onset of tumor appearance and the mean survival time of tumor-bearing host mice were beneficially influenced. Occasional animals could be cured of up to 10(5) tumor cells (1--10 cells of MNB are lethal). This level of tumor cytotoxicity approaches that of tolerance-dose chemotherapy and is without demonstrable side-effects. HLc from patients who had just received = 3,000 rads fractionated therapeutic X-irradiation were equally effective as HLc from control non-irradiated donors when assayed at equivalent HLc : tumor cell ratios. HLc could also inhibit MNB tumor cell growth in the ascitic form, confirming in vivo activity. Overall, HLc appeared almost as active as rat spleen cells in mediating a useful anti-tumor ADCC. This approach may ultimately prove useful in man, especially in the peritoneal cavity, and is currently limited only by the need to develop appropriate antisera. It is proposed and emphasized that such antisera need not necessarily be directed at tumor-specific antigens. Organ-specific antibodies such are already known to develop spontaneously in some human auto-immune diseases might be equally useful and are a naturally occurring potential source of appropriately expressed genetic material.

  1. A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice

    PubMed Central

    Milligan, Gregg N.; Sarathy, Vanessa V.; Infante, Ernesto; Li, Li; Campbell, Gerald A.; Beatty, P. Robert; Harris, Eva; Barrett, Alan D. T.; Bourne, Nigel

    2015-01-01

    Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals. PMID:25938762

  2. A study of the uptake of toluidine blue O by Porphyromonas gingivalis and the mechanism of lethal photosensitization.

    PubMed

    Bhatti, M; MacRobert, A; Meghji, S; Henderson, B; Wilson, M

    1998-09-01

    The purpose of the study was to determine the distribution of the photosensitizer toluidine blue O (TBO) within Porphyromonas gingivalis and the possible mechanism(s) involved in the lethal photosensitization of this organism. The distribution of TBO was determined by incubating P. gingivalis with tritiated TBO (3H-TBO) and fractionating the cells into outer membrane (OM), plasma membrane (PM), cytoplasmic proteins, other cytoplasmic constituents and DNA. The percentage of TBO in each of the fractions was found to be, 86.7, 5.4, 1.9, 5.7 and 0.3%, respectively. The involvement of cytotoxic species in the lethal photosensitization induced by light from a heliumneon (HeNe) laser and TBO was investigated by using deuterium oxide (D2O), which prolongs the lifetime of singlet oxygen, and the free radical and signlet oxygen scavenger L-tryptophan. There were 9.0 log10 and 2 log10 reductions in the presence of D2O and H2O (saline solutions), respectively, at a light dose of 0.44 J (energy density = 0.22 J/cm2), suggesting the involvement of singlet oxygen. Decreased kills were attained in the presence of increasing concentrations of L-tryptophan. The effect of lethal photosensitization on whole cell proteins was determined by measuring tryptophan fluorescence, which decreased by 30% using 4.3 J (energy density = 4.3 J/cm2) of light. Effects on the OM and PM proteins were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. There was evidence of change in the molecular masses of several PM proteins and OM proteins compared to controls. There was evidence of damage to the DNA obtained from irradiated cells. Scanning electron microscopic studies showed that there was coaggregation of P. gingivalis cells when sensitized and then exposed to laser light. These results suggest that lethal photosensitization of P. gingivalis may involve changes in OM and/or PM proteins and DNA damage mediated by singlet oxygen.

  3. How many loci on the X-chromosome of Drosophila melanogaster can mutate to recessive lethals

    SciTech Connect

    Abrahamson, S.; Wuergler, F.E.; DeJongh, C.; Meyer, H.U.

    1980-01-01

    The sensitivity of the sex-linked recessive lethal test is due to the fact that a very large number of loci are included in the mutation study. From extensive studies on the spontaneous sex-linked recessive lethal frequency and spontaneous specific locus mutation rates, it is possible to derive an estimate of the number of loci included in the recessive lethal test. The average number derived from three estimates on male and female germ cells in 563 loci. A second independent approach derives from published data which analyzed short regions of the genome and the proportion of loci within these regions which mutate to lethality. This analysis suggests that 830 loci are potentially lethal mutables. We describe the reasons for concluding that 600 to 800 loci of the approximately 1000 loci on the X-chromosome are involved in the X-linked recessive lethal test.

  4. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida.

    PubMed

    Rico, Andreu; Sabater, Consuelo; Castillo, María-Ángeles

    2016-05-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems.

  5. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida.

    PubMed

    Rico, Andreu; Sabater, Consuelo; Castillo, María-Ángeles

    2016-05-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems. PMID:26874341

  6. RKN Lethal DB: A database for the identification of Root Knot Nematode (Meloidogyne spp.) candidate lethal genes

    PubMed Central

    Ismail, Ahmed; Matthews, Benjamin F; Alkharouf, Nadim W

    2012-01-01

    Root Knot nematode (RKN; Meloidogyne spp.) is one of the most devastating parasites that infect the roots of hundreds of plant species. RKN cannot live independently from their hosts and are the biggest contributors to the loss of the world's primary foods. RNAi gene silencing studies have demonstrated that there are fewer galls and galls are smaller when RNAi constructs targeted to silence certain RKN genes are expressed in plant roots. We conducted a comparative genomics analysis, comparing RKN genes of six species: Meloidogyne Arenaria, Meloidogyne Chitwoodi, Meloidogyne Hapla, Meloidogyne Incognita, Meloidogyne Javanica, and Meloidogyne Paranaensis to that of the free living nematode Caenorhabditis elegans, to identify candidate genes that will be lethal to RKN when silenced or mutated. Our analysis yielded a number of such candidate lethal genes in RKN, some of which have been tested and proven to be effective in soybean roots. A web based database was built to house and allow scientists to search the data. This database will be useful to scientists seeking to identify candidate genes as targets for gene silencing to confer resistance in plants to RKN. Availability The database can be accessed from http://bioinformatics.towson.edu/RKN/ PMID:23144556

  7. Effect of irradiation on testicular cells of opossum.

    PubMed

    Prasad, N; Prasad, R; Bushong, S C; North, L B

    1977-07-01

    Five months old male opossums were exposed to 5000 rd wholebody 60Co gamma-radiation. Testes tissues from animals sacrificed at 16, 40 and 90 hours post-irradiation and from nonirradiated animales were used for enzymatic and histological studies. Electrophoretic pattern of lactate dehydrogenase and glucose-6-phosphate dehydrogenase was slightly disturbed in early hours in irradiated animals, but it did not persist beyond 40 hours postirradiation. Histological study indicates 31% survival of type A spermatogonia suggesting high radioresistance of testes tissue in comparison to other animals.

  8. Total lymphoid irradiation and discordant cardiac xenografts

    SciTech Connect

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. )

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  9. Studying survivors of near-lethal suicide attempts as a proxy for completed suicide in prisons.

    PubMed

    Rivlin, Adrienne; Fazel, Seena; Marzano, Lisa; Hawton, Keith

    2012-07-10

    Suicides in prisons are common. There is a pressing need to understand more about the causes and prevention of prisoner suicides. A particularly informative approach is through studying survivors of near-lethal suicide attempts. However, the extent to which this approach is a good proxy for completed suicide requires verification. In this article we aimed to assess (1) the extent to which male and female prisoners who made near-lethal suicide attempts in prison are similar to prisoners who die by suicide; (2) the suicidal intent of those making near-lethal suicide attempts; and (3) the applicability of the Suicide Intent Scale in prisons. Survivors of near-lethal suicide attempts and prisoners who died by suicide were compared on sociodemographic and criminological characteristics. The suicidal intent of prisoners engaging in near-lethal self-harm was assessed using Beck's Suicide Intent Scale. There were no significant differences when the sociodemographic and criminological profiles of prisoners who made near-lethal suicide attempts and those who died by suicide were compared, except that male prisoners who made near-lethal suicide attempts were somewhat younger. Most prisoners carrying out near-lethal acts had high suicidal intent. However, some questions in the Suicide Intent Scale were inappropriate for assessing intent in prisoners. Prisoners who survive near-lethal self-harm would appear to be a valid proxy for those who die by suicide in prison. The Suicide Intent Scale requires some modifications for use in prisons.

  10. Risks of non-lethal weapon use: case studies of three French victims of stinger grenades.

    PubMed

    Scolan, V; Herry, C; Carreta, M; Stahl, C; Barret, L; Romanet, J P; Paysant, F

    2012-11-30

    The development of non-lethal weapons started in the 1960s. In France, they have been used by the police for about 10 years. We relate the cases of three French women, victims of stinger grenades, non-lethal weapons recently adopted by the French law enforcement to distract and disperse crowds. The three victims presented serious injuries requiring emergency surgical care. One lost her eye. Based on these cases, we discuss the lethal character of these weapons and propose measures to be taken to prevent their dramatic consequences. Although the danger is obviously less than for firearms, stinger grenades are nonetheless potentially lethal and cause serious physical injuries.

  11. Collateral Lethality: A new therapeutic strategy in oncology

    PubMed Central

    Muller, Florian L.; Aquilanti, Elisa A.; DePinho, Ronald A.

    2016-01-01

    Genomic deletion of tumor suppressor genes (TSG) is a rite of passage for virtually all human cancers. The synthetic lethal paradigm has provided a framework for the development of molecular targeted therapeutics that are functionally linked to the loss of specific TSG functions. In the course of genomic events that delete TSGs, a large number of genes with no apparent direct role in tumor promotion also sustain deletion as a result of chromosomal proximity to the target TSG. In this perspective, we review the novel concept of “collateral lethality”, which has served to identify cancer-specific therapeutic vulnerabilities resulting from co-deletion of passenger genes neighboring TSG. The large number of collaterally deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities presenting novel opportunities for the development of personalized anti-neoplastic therapies. PMID:26870836

  12. DDE in birds: Lethal residues and loss rates

    USGS Publications Warehouse

    Stickel, W.H.; Stickel, L.F.; Dyrland, R.A.; Hughes, D.L.

    1984-01-01

    Lethal brain residues of DDE were determined experimentally in four species of wild birds (male common grackels (Quiscalus quiscula ), immature female red-winged blackbirds (Agelaius phoeniceus ), adult male brown-headed cowbirds (Molathrus ater ), and immature female starlings (Sturnus vulgaris ) given dietary dosage of 1,500 ppm DDE until one-half had died, then sacrificing the survivors, chemically analyzing the tissues, and comparing results in dead birds and survivors. In all species, residues of 300 to 400 ppm of DDE in the brain were considered to show increasing likelihood of death from DDE, confirming results of an earlier study with a single species. Body residues (ppm wet weight) were not diagnostic, overlapping grossly in dead birds and survivors, but averaging higher in survivors.

  13. Aroclor 1254 residues in birds: Lethal levels and loss rates

    USGS Publications Warehouse

    Stickel, W.H.; Stickel, L.F.; Dyrland, R.A.; Hughes, D.L.

    1984-01-01

    Lethal residues of polychlorinated biphenyls (PCBs) were determined experimentally in four species of wild birds (male common grackles (Quiscalus quiscula ), immature female red-winged blackbirds (Agelaius phoeniceus ), adult male brown-headed cowbirds (Molothrus ater ) and immature female starlings (Sturnus vulgaris)) given dietary dosage of 1,500 ppm of Aroclor 1254) until one-half had died, sacrificing the survivors, chemically analyzing the tissues, and comparing results in dead birds and survivors. For all species, residues of 310 ppm or higher in the brain showed increasing likelihood of death from PCB poisoning. Residues in dead birds did not differ among species except for starlings (Sturnus vulgaris ), which averaged slightly lower than the others. However, the species differed in the length of time to 50% mortality and in the levels of PCBs in brains at sacrifice.

  14. Non-lethal laser dazzling as a personnel countermeasure

    NASA Astrophysics Data System (ADS)

    Shannon, David C.

    2013-10-01

    Optical distraction is likely one of the original and simpler optical countermeasure concepts with a technology history dating back to the 1800's. The objective is to distract or suppress either equipment or personnel with optical radiation from a safe distance. This paper is intended to review and expand on the concepts presented at the 2012 SPIE Security and Defense meeting; "Non-Lethal Optical Interruption (Dazzling): Technology, Devices, and Scenarios". The information that follows will focus primarily on the technology and techniques associated with the safe laser dazzling of personnel. Key product design guidelines will be highlighted and reviewed. Recent advances in laser technology and their associated impact on hand-held devices will also be discussed. Finally, the author will offer his opinion on the growth rate of military and non-military markets for laser dazzlers.

  15. Clinical Effects and Lethal and Forensic Aspects of Propofol*

    PubMed Central

    Levy, Richard J.

    2010-01-01

    Propofol is a potent intravenous anesthetic agent that rapidly induces sedation and unconsciousness. The potential for propofol dependency, recreational use and abuse has only recently been recognized and several cases of accidental overdose and suicide have emerged. In addition, the first documented case of murder using propofol was reported a few months ago and a high profile case of suspected homicide with propofol is currently under investigation. A number of analytical methods have been employed to detect and quantify propofol concentrations in biological specimens. The reported propofol related deaths and post-mortem blood and tissue levels are reviewed. Importantly, limitations of propofol detection are discussed and future considerations are presented. Because propofol has the potential for diversion with lethal consequences, the forensic scientist must have a basic understanding of its clinical indications and uses, pharmacologic properties, and detection methods. In addition, medical institutions should develop systems to prevent and detect diversion of this potential drug of abuse. PMID:20950316

  16. Chikungunya fever: Atypical and lethal cases in the Western hemisphere

    PubMed Central

    Torres, Jaime R.; Leopoldo Códova G.; Castro, Julio S.; Rodríguez, Libsen; Saravia, Víctor; Arvelaez, Joanne; Ríos-Fabra, Antonio; Longhi, María A.; Marcano, Melania

    2014-01-01

    A large epidemic of Chikungunya fever currently affects the Caribbean, Central and South America. Despite a high number of reported cases, little is known on the occurrence of severe clinical complications. We describe four Venezuelan patients with a severe and/or lethal course who exhibit unusual manifestations of the disease. Case 1 describes a 75 year-old man with rapid onset of septic shock and multi-organ failure. Cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock, severe purpuric lesions and a distinct area large of necrosis in the nasal region. Case 4 depicts a splenectomized woman with shock, generalized purpuric lesions, bullous dermatosis and acronecrosis of an upper limb. Chikungunya fever in the Western hemisphere may also associate with atypical and severe manifestations. Some patients experience a life-threatening, aggressive clinical course, with rapid deterioration and death due to multisystem failure. PMID:26793440

  17. Synthetic lethal approaches exploiting DNA damage in aggressive myeloma

    PubMed Central

    Cottini, Francesca; Hideshima, Teru; Suzuki, Rikio; Tai, Yu-Tzu; Bianchini, Giampaolo; Richardson, Paul G.; Anderson, Kenneth C.; Tonon, Giovanni

    2015-01-01

    Ongoing DNA damage is a common feature of epithelial cancers. Here we show that tumor cells derived from multiple myeloma (MM), a disease of clonal plasma cells, demonstrate DNA replicative stress leading to DNA damage. We identified a poor prognosis subset of MM with extensive chromosomal instability and replicative stress which rely on ATR to compensate for DNA replicative stress; conversely, silencing of ATR or treatment with a specific ATR inhibitor triggers MM cell apoptosis. We show that oncogenes such as MYC induce DNA damage in MM cells not only by increased replicative stress, but also via increased oxidative stress, and that ROS-inducer piperlongumine triggers further DNA damage and apoptosis. Importantly, ATR inhibition combined with piperlongumine triggers synergistic MM cytotoxicity. This synthetic lethal approach, enhancing oxidative stress while concomitantly blocking replicative stress response, provides a novel combination targeted therapy to address an unmet medical need in this subset of MM. PMID:26080835

  18. Lethal hypophosphatasia, spur type: case report and fetopathological study.

    PubMed

    Vandevijver, N; De Die-Smulders, C E; Offermans, J P; Van Der Linden, E S; Arends, J W; Sastrowijoto, S H; Moerman, P; Fryns, J P

    1998-01-01

    Lethal hypophosphatasia, spur type: case report and fetopathological study: Hypophosphatasia (HP) is characterised by severe undermineralisation of the skeleton owing to deficiency of tissue nonspecific alkaline phosphatase. Clinically a perinatal, infantile, childhood and adult type is distinguished. Clinical signs in the perinatal type of HP show considerable overlap with other skeletal dysplasias such as osteogenesis imperfecta type IIA and type IIC, and achondrogenesis type IA. If present, "spurs" of the limbs are diagnostic for HP. We present a prenatally diagnosed case of HP and discuss the differential diagnosis based on clinical, radiological and pathological findings. Our findings indicate that two types of spurs can be distinguished in hypophosphatasia: midshaft type and joint type. PMID:9777343

  19. [Medical aspects of common non-lethal weapons].

    PubMed

    Kunz, Sebastian Niko; Grove, Christina; Monticelli, Fabio

    2014-03-01

    The development and provision of non-lethal weapons (NLW) allow military and law enforcement personnel to exploit gradual engagement in countering potentially hazardous threats. Chemical, kinetic and electrical weapons systems are used to curb violence in civilian crowds. With inappropriate usage, these technologies can cause potentially fatal injuries that are not only of clinical, but also of legal relevance. In this context, the practicing physician is faced with treatment as well as assessment issues of new forms of injuries. In order to assure medical care and to be able to draw competent expert's conclusions, a detailed knowledge of the medical effects of these NLW is necessary. The review at hand presents today's most popular NLW and gives an overview of their possible injury potential and required treatments.

  20. A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease.

    PubMed

    Metallinos, D L; Bowling, A T; Rine, J

    1998-06-01

    Lethal White Foal Syndrome is a disease associated with horse breeds that register white coat spotting patterns. Breedings between particular spotted horses, generally described as frame overo, produce some foals that, in contrast to their parents, are all white or nearly all white and die shortly after birth of severe intestinal blockage. These foals have aganglionosis characterized by a lack of submucosal and myenteric ganglia from the distal small intestine to the large intestine, similar to human Hirschsprung Disease. Some sporadic and familial cases of Hirschsprung Disease are due to mutations in the endothelin B receptor gene (EDNRB). In this study, we investigate the role of EDNRB in Lethal White Foal Syndrome. A cDNA for the wild-type horse endothelin-B receptor gene was cloned and sequenced. In three unrelated lethal white foals, the EDNRB gene contained a 2-bp nucleotide change leading to a missense mutation (I118K) in the first transmembrane domain of the receptor, a highly conserved region of this protein among different species. Seven additional unrelated lethal white foal samples were found to be homozygous for this mutation. No other homozygotes were identified in 138 samples analyzed, suggesting that homozygosity was restricted to lethal white foals. All (40/40) horses with the frame overo pattern (a distinct coat color pattern that is a subset of overo horses) that were tested were heterozygous for this allele, defining a heterozygous coat color phenotype for this mutation. Horses with tobiano markings included some carriers, indicating that tobiano is epistatic to frame overo. In addition, horses were identified that were carriers but had no recognized overo coat pattern phenotype, demonstrating the variable penetrance of the mutation. The test for this mutant allele can be utilized in all breeds where heterozygous animals may be unknowingly bred to each other including the Paint Horse, Pinto horse, Quarter Horse, Miniature Horse, and Thoroughbred.

  1. A Lethal Murine Infection Model for Dengue Virus 3 in AG129 Mice Deficient in Type I and II Interferon Receptors Leads to Systemic Disease

    PubMed Central

    Sarathy, Vanessa V.; White, Mellodee; Li, Li; Gorder, Summer R.; Pyles, Richard B.; Campbell, Gerald A.; Milligan, Gregg N.

    2014-01-01

    ABSTRACT The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. IMPORTANCE Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness

  2. Tumor expression of adiponectin receptor 2 and lethal prostate cancer

    PubMed Central

    Fiorentino, Michelangelo; Kelly, Rachel; Gerke, Travis; Jordahl, Kristina; Sinnott, Jennifer A.; Giovannucci, Edward L.; Loda, Massimo; Mucci, Lorelei A.; Finn, Stephen

    2015-01-01

    To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians’ Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2–3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression. PMID:25863129

  3. RAS Synthetic Lethal Screens Revisited: Still Seeking the Elusive Prize?

    PubMed

    Downward, Julian

    2015-04-15

    The RAS genes are critical oncogenic drivers activated by point mutation in some 20% of human malignancies. However, no pharmacologic approaches to targeting RAS proteins directly have yet succeeded, leading to suggestions that these proteins may be "undruggable." This has led to two alternative indirect approaches to targeting RAS function in cancer. One has been to target RAS signaling pathways downstream at tractable enzymes such as kinases, particularly in combination. The other, which is the focus of this review, has been to seek targets that are essential in cells bearing an activated RAS oncogene, but not those without. This synthetic lethal approach, while rooted in ideas from invertebrate genetics, has been inspired most strongly by the successful use of PARP inhibitors, such as olaparib, in the clinic to treat BRCA defective cancers. Several large-scale screens have been carried out using RNA interference-mediated expression silencing to find genes that are uniquely essential to RAS-mutant but not wild-type cells. These screens have been notable for the low degree of overlap between their results, with the possible exception of proteasome components, and have yet to lead to successful new clinical approaches to the treatment of RAS-mutant cancers. Possible reasons for these disappointing results are discussed here, along with a reevaluation of the approaches taken. On the basis of experience to date, RAS synthetic lethality has so far fallen some way short of its original promise and remains unproven as an approach to finding effective new ways of tackling RAS-mutant cancers. Clin Cancer Res; 21(8); 1802-9. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers." PMID:25878361

  4. An exome sequencing strategy to diagnose lethal autosomal recessive disorders.

    PubMed

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-03-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0-4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.

  5. An exome sequencing strategy to diagnose lethal autosomal recessive disorders

    PubMed Central

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-01-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies. PMID:24961629

  6. RAS Synthetic Lethal Screens Revisited: Still Seeking the Elusive Prize?

    PubMed Central

    Downward, Julian

    2015-01-01

    The RAS genes are critical oncogenic drivers activated by point mutation in some 20% of human malignancies. However, no pharmacological approaches to targeting RAS proteins directly have yet succeeded, leading to suggestions that these proteins may be “undruggable.” This has led to two alternative indirect approaches to targeting RAS function in cancer. One has been to target RAS signaling pathways downstream at tractable enzymes such as kinases, particularly in combination. The other, which is the focus of this review, has been to seek targets that are essential in cells bearing an activated RAS oncogene, but not those without. This synthetic lethal approach, while rooted in ideas from invertebrate genetics, has been inspired most strongly by the successful use of PARP inhibitors, such as olaparib, in the clinic to treat BRCA defective cancers. Several large-scale screens have been carried out using RNA interference-mediated expression silencing to find genes that are uniquely essential to RAS mutant but not wild type cells. These screens have been notable for the low degree of overlap between their results, with the possible exception of proteasome components, and have yet to lead to successful new clinical approaches to the treatment of RAS mutant cancers. Possible reasons for these disappointing results are discussed here, along with a re-evaluation of the approaches taken. Based on experience to date, RAS synthetic lethality has so far fallen some way short of its original promise and remains unproven as an approach to finding effective new ways of tackling RAS mutant cancers. PMID:25878361

  7. Lethal Mutagenesis of Poliovirus Mediated by a Mutagenic Pyrimidine Analogue▿

    PubMed Central

    Graci, Jason D.; Harki, Daniel A.; Korneeva, Victoria S.; Edathil, Jocelyn P.; Too, Kathleen; Franco, David; Smidansky, Eric D.; Paul, Aniko V.; Peterson, Blake R.; Brown, Daniel M.; Loakes, David; Cameron, Craig E.

    2007-01-01

    Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase-mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension, and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous base-pairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture, owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses. PMID:17686844

  8. Development of status epilepticus, sustained calcium elevations and neuronal injury in a rat survival model of lethal paraoxon intoxication.

    PubMed

    Deshpande, Laxmikant S; Carter, Dawn S; Phillips, Kristin F; Blair, Robert E; DeLorenzo, Robert J

    2014-09-01

    Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague-Dawley rats injected with POX (4mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6-8min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7-10Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2mg/kg, i.p., 2-PAM, 25mg/kg, i.m. and diazepam, 5mg/kg, i.p.) promptly stopped SE and reduced acute mortality to 12% and chronic mortality to 18%. This model is ideally suited to test effective countermeasures against lethal POX exposure. Animals that survived the POX SE manifested prolonged elevations in hippocampal [Ca(2+)]i (Ca(2+) plateau) and significant multifocal neuronal injury. POX SE induced Ca(2+) plateau had its origin in Ca(2+) release from intracellular Ca(2+) stores since inhibition of ryanodine/IP3 receptor lowered elevated Ca(2+) levels post SE. POX SE induced neuronal injury and alterations in Ca(2+) dynamics may underlie some of the long term morbidity associated with OP toxicity.

  9. Low salinity enhances NI-mediated oxidative stress and sub-lethal toxicity to the green shore crab (Carcinus maenas).

    PubMed

    Blewett, Tamzin A; Wood, Chris M

    2015-12-01

    Nickel (Ni) is a metal of environmental concern, known to cause toxicity to freshwater organisms by impairing ionoregulation and/or respiratory gas exchange, and by inducing oxidative stress. However, little is known regarding how nickel toxicity is influenced by salinity. In the current study we investigated the salinity-dependence and mechanisms of sub-lethal Ni toxicity in a euryhaline crab (Carcinus maenas). Crabs were acclimated to three experimental salinities--20, 60 and 100% seawater (SW)--and exposed to 3mg/L Ni for 24h or 96 h. Tissues were dissected for analysis of Ni accumulation, gills were taken for oxidative stress analysis (catalase activity and protein carbonyl content), haemolymph ions were analysed for ionoregulatory disturbance, and oxygen consumption was determined in exercised crabs after 96 h of Ni exposure. Total Ni accumulation was strongly dependant on salinity, with crabs from 20% SW displaying the highest tissue Ni burdens after both 24 and 96-h exposures. After 96 h of exposure, the highest accumulation of Ni occurred in the posterior (ionoregulatory) gills at the lowest salinity, 20% SW. Posterior gill 8 exhibited elevated protein carbonyl levels and decreased catalase activity after Ni exposure, but only in 20% SW. Similarly, decreased levels of haemolymph Mg and K and an increased level of Ca were recorded but only in crabs exposed to Ni for 96 h in 20% SW. Oxygen consumption after exercise was also inhibited in crabs exposed to Ni in 20% SW. These data show for the first time the simultaneous presence of all three modes of sub-lethal Ni toxicity in exposed animals, and indicate a strong salinity dependence of sub-lethal Ni toxicity to the euryhaline crab, C. maenas, a pattern that corresponded to tissue Ni accumulation. PMID:26233920

  10. Photoinduced lethal and sublethal toxicity of retene, a polycyclic aromatic hydrocarbon derived from resin acid, to coregonid larvae.

    PubMed

    Vehniäinen, Eeva-Riikka; Häkkinen, Jani; Oikari, Aimo

    2003-12-01

    A comparative investigation on the acute phototoxicity of retene to vendace (Coregonus albula) and whitefish (C. lavaretus), both having pelagial larvae in spring, was conducted. To test the concept of early warning of sublethal biomarkers in relation to lethality to posthatch stages, we examined the effects of ultraviolet-B (UV-B) and retene on the levels of cytochrome P4501A (CYP1A) and heat shock protein 70 (HSP70) by exposing the animals to elevated levels of these factors for 48 and 72 h, respectively. Whereas UV-B and retene on their own were not lethal, simultaneous retene and UV-B exposure caused very high mortality to both species. The median lethal concentration (LC50; i.e., the concentration at which half of the larvae died) of retene as a precursor was 41 g/L for vendace and 15 to 16 microg/L, depending on the UV-B dose, for whitefish. Retene evoked substantial induction of CYP1A in larvae of both species, and UV-B induced CYP1A in whitefish. In vendace, no effect on HSP70 levels by any factor was observed. In whitefish, however, UV-B radiation and water retene alone upregulated HSP70, but no additive response was detected. The CYPIA is a biomarker of exposure to retene in both species. The HSP70 is an early warning signal of UV-B exposure in whitefish. As a species, vendace appears to be more resistant than whitefish to the phototoxicity of retene, as indicated by the higher tolerance. PMID:14713041

  11. Selective reconstitution of liver cholesterol biosynthesis promotes lung maturation but does not prevent neonatal lethality in Dhcr7 null mice

    PubMed Central

    Yu, Hongwei; Li, Man; Tint, G Stephen; Chen, Jianliang; Xu, Guorong; Patel, Shailendra B

    2007-01-01

    Background Targeted disruption of the murine 3β-hydroxysterol-Δ7-reductase gene (Dhcr7), an animal model of Smith-Lemli-Opitz syndrome, leads to loss of cholesterol synthesis and neonatal death that can be partially rescued by transgenic replacement of DHCR7 expression in brain during embryogenesis. To gain further insight into the role of non-brain tissue cholesterol deficiency in the pathophysiology, we tested whether the lethal phenotype could be abrogated by selective transgenic complementation with DHCR7 expression in the liver. Results We generated mice that carried a liver-specific human DHCR7 transgene whose expression was driven by the human apolipoprotein E (ApoE) promoter and its associated liver-specific enhancer. These mice were then crossed with Dhcr7+/- mutants to generate Dhcr7-/- mice bearing a human DHCR7 transgene. Robust hepatic transgene expression resulted in significant improvement of cholesterol homeostasis with cholesterol concentrations increasing to 80~90 % of normal levels in liver and lung. Significantly, cholesterol deficiency in brain was not altered. Although late gestational lung sacculation defect reported previously was significantly improved, there was no parallel increase in postnatal survival in the transgenic mutant mice. Conclusion The reconstitution of DHCR7 function selectively in liver induced a significant improvement of cholesterol homeostasis in non-brain tissues, but failed to rescue the neonatal lethality of Dhcr7 null mice. These results provided further evidence that CNS defects caused by Dhcr7 null likely play a major role in the lethal pathogenesis of Dhcr7-/- mice, with the peripheral organs contributing the morbidity. PMID:17408495

  12. Low salinity enhances NI-mediated oxidative stress and sub-lethal toxicity to the green shore crab (Carcinus maenas).

    PubMed

    Blewett, Tamzin A; Wood, Chris M

    2015-12-01

    Nickel (Ni) is a metal of environmental concern, known to cause toxicity to freshwater organisms by impairing ionoregulation and/or respiratory gas exchange, and by inducing oxidative stress. However, little is known regarding how nickel toxicity is influenced by salinity. In the current study we investigated the salinity-dependence and mechanisms of sub-lethal Ni toxicity in a euryhaline crab (Carcinus maenas). Crabs were acclimated to three experimental salinities--20, 60 and 100% seawater (SW)--and exposed to 3mg/L Ni for 24h or 96 h. Tissues were dissected for analysis of Ni accumulation, gills were taken for oxidative stress analysis (catalase activity and protein carbonyl content), haemolymph ions were analysed for ionoregulatory disturbance, and oxygen consumption was determined in exercised crabs after 96 h of Ni exposure. Total Ni accumulation was strongly dependant on salinity, with crabs from 20% SW displaying the highest tissue Ni burdens after both 24 and 96-h exposures. After 96 h of exposure, the highest accumulation of Ni occurred in the posterior (ionoregulatory) gills at the lowest salinity, 20% SW. Posterior gill 8 exhibited elevated protein carbonyl levels and decreased catalase activity after Ni exposure, but only in 20% SW. Similarly, decreased levels of haemolymph Mg and K and an increased level of Ca were recorded but only in crabs exposed to Ni for 96 h in 20% SW. Oxygen consumption after exercise was also inhibited in crabs exposed to Ni in 20% SW. These data show for the first time the simultaneous presence of all three modes of sub-lethal Ni toxicity in exposed animals, and indicate a strong salinity dependence of sub-lethal Ni toxicity to the euryhaline crab, C. maenas, a pattern that corresponded to tissue Ni accumulation.

  13. [Animal experimentation, animal welfare and scientific research].

    PubMed

    Tal, H

    2013-10-01

    Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals. PMID:24660572

  14. [Animal experimentation, animal welfare and scientific research].

    PubMed

    Tal, H

    2013-10-01

    Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals.

  15. Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

    PubMed Central

    2012-01-01

    Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality) and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in feeding reduction. However, there

  16. Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge.

    PubMed

    Sofer-Podesta, Carolina; Ang, John; Hackett, Neil R; Senina, Svetlana; Perlin, David; Crystal, Ronald G; Boyer, Julie L

    2009-04-01

    Pneumonic plague, caused by inhalation of Yersinia pestis, represents a major bioterrorism threat for which no vaccine is available. Based on the knowledge that genetic delivery of monoclonal antibodies (MAbs) with adenovirus (Ad) gene transfer vectors results in rapid, high-level antibody expression, we evaluated the hypothesis that Ad-mediated delivery of a neutralizing antibody directed against the Y. pestis V antigen would protect mice against a Y. pestis challenge. MAbs specific for the Y. pestis V antigen were generated, and the most effective in protecting mice against a lethal intranasal Y. pestis challenge was chosen for further study. The coding sequences for the heavy and light chains were isolated from the corresponding hybridoma and inserted into a replication-defective serotype 5 human Ad gene transfer vector (AdalphaV). Western analysis of AdalphaV-infected cell supernatants demonstrated completely assembled antibodies reactive with V antigen. Following AdalphaV administration to mice, high levels of anti-V antigen antibody titers were detectable as early as 1 day postadministration, peaked by day 3, and remained detectable through a 12-week time course. When animals that received AdalphaV were challenged with Y. pestis at day 4 post-AdalphaV administration, 80% of the animals were protected, while 0% of control animals survived (P < 0.01). Ad-mediated delivery of a V antigen-neutralizing antibody is an effective therapy against plague in experimental animals and could be developed as a rapidly acting antiplague therapeutic.

  17. Cultured cells from a severe combined immunodeficient mouse have a slower than normal rate of repair of potentially lethal damage sensitive to hypertonic treatment

    SciTech Connect

    Kimura, H.; Terado, T.; Ikebuchi, M.; Aoyama, T.; Komatsu, K.; Nozawa, A.

    1995-05-01

    The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of DNA damage were examined in fibroblasts of the severe combined immunodeficient (scid) mouse. These cells are hypersensitive to ionizing radiation because of a deficiency in the repair of double-strand breaks. Hypertonic treatment caused radiosensitization due to a fixation of potentially lethal damage (PLD) in scid cells, demonstrating that scid cells normally repair PLD. To assess the kinetics of the repair of PLD, hypertonic treatment was delayed for various times after irradiation. Potentially lethal damage was repaired during these times in isotonic medium at 37{degrees}C. It was found that the rate of repair of PLD was much slower in scid cells than in BALB/c 3T3 cells, which have a {open_quotes}wild-type{close_quotes} level of radiosensitivity. This fact indicates that the scid mutation affects the type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid cells containing fragments of human chromosome 8, which complements the radiosensitivity of the scid cells, the rate of repair was restored to a normal level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD which is sensitive to hypertonic treatment. 29 refs., 3 figs.

  18. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    PubMed

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult. PMID:26425905

  19. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    PubMed

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult.

  20. Integrated microfluidic technology for sub-lethal and behavioral marine ecotoxicity biotests

    NASA Astrophysics Data System (ADS)

    Huang, Yushi; Reyes Aldasoro, Constantino Carlos; Persoone, Guido; Wlodkowic, Donald

    2015-06-01

    Changes in behavioral traits exhibited by small aquatic invertebrates are increasingly postulated as ethically acceptable and more sensitive endpoints for detection of water-born ecotoxicity than conventional mortality assays. Despite importance of such behavioral biotests, their implementation is profoundly limited by the lack of appropriate biocompatible automation, integrated optoelectronic sensors, and the associated electronics and analysis algorithms. This work outlines development of a proof-of-concept miniaturized Lab-on-a-Chip (LOC) platform for rapid water toxicity tests based on changes in swimming patterns exhibited by Artemia franciscana (Artoxkit M™) nauplii. In contrast to conventionally performed end-point analysis based on counting numbers of dead/immobile specimens we performed a time-resolved video data analysis to dynamically assess impact of a reference toxicant on swimming pattern of A. franciscana. Our system design combined: (i) innovative microfluidic device keeping free swimming Artemia sp. nauplii under continuous microperfusion as a mean of toxin delivery; (ii) mechatronic interface for user-friendly fluidic actuation of the chip; and (iii) miniaturized video acquisition for movement analysis of test specimens. The system was capable of performing fully programmable time-lapse and video-microscopy of multiple samples for rapid ecotoxicity analysis. It enabled development of a user-friendly and inexpensive test protocol to dynamically detect sub-lethal behavioral end-points such as changes in speed of movement or distance traveled by each animal.