Science.gov

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. Murine survival of lethal irradiation with the use of human umbilical cord blood

    SciTech Connect

    Ende, N.; Ponzio, N.M.; Athwal, R.S.; Giuliani, D.C. ); Ende, M. )

    1992-01-01

    The authors have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over seventy percent of mice injected with HUCB survived 900 cGy or irradiation, which produced 100% deaths in the uninjected control animals. Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti-Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation.

  3. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  4. 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

  5. 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

  6. Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation

    SciTech Connect

    Brecher, G.; Neben, S.; Yee, M.; Bullis, J.; Cronkite, E.P.

    1988-08-01

    Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initially in all hosts. Between 55% and 92% of the animals became 100% host type by 12-24 weeks after transfusion in three separate experiments. To explore whether the temporary repopulation by donor cells was due to short-lived stem cells, the marrows of several primary hosts were transfused into secondary, lethally irradiated hosts. Some of the retransplanted primary donor and host cells persisted only temporarily. It is suggested that some of the donor stem cells in both the primary and secondary hosts had an intrinsically shortened life span.

  7. Effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice

    SciTech Connect

    Boggs, S.S.; Boggs, D.R.; Patrene, K.D.

    1989-06-01

    Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of /sup 59/Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and /sup 59/Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen /sup 59/Fe and a decrease in marrow /sup 59/Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen /sup 59/Fe uptake but the marrow /sup 59/Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.

  8. 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

  9. Trisomic hemopoietic stem cells of fetal origin restore hemopoiesis in lethally irradiated mice

    SciTech Connect

    Herbst, E.W.; Pluznik, D.H.; Gropp, A.; Uthgenannt, H.

    1981-03-13

    Autosomal trisomy in the mouse is invariably associated with fetal or early postnatal death. Hemopoietic stem cells from fetuses trisomic for chromosome 12 or 19 can be rescued by transplantation into lethally irradiated mice. These trisomic cells restore hemopoiesis, including lymphopoiesis, in the irradiated mice and establish a permanent and almost complete engraftment. There is no evidence that hemopoietic cells with trisomy 12 or 19 are cytogenetically unstable.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

    2015-01-01

    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

  15. 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

  16. The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair.

    PubMed

    Rajagopalan, Malolan S; Gupta, Kanika; Epperly, Michael W; Franicola, Darcy; Zhang, Xichen; Wang, Hong; Zhao, Hong; Tyurin, Vladimir A; Pierce, Joshua G; Kagan, Valerian E; Wipf, Peter; Kanai, Anthony J; Greenberger, Joel S

    2009-01-01

    It was unknown if a mitochondria-targeted nitroxide (JP4-039) could augment potentially lethal damage repair (PLDR) of cells in quiescence. We evaluated 32D cl 3 murine hematopoietic progenitor cells which were irradiated and then either centrifuged to pellets (to simulate PLDR conditions) or left in exponential growth for 0, 24, 48 or 72 h. Pelleted cells demonstrated cell cycle arrest with a greater percentage in the G(1)-phase than did exponentially growing cells. Irradiation survival curves demonstrated a significant radiation damage mitigation effect of JP4-039 over untreated cells in cells pelleted for 24 h. No significant radiation mitigation was detected if drugs were added 48 or 72 h after irradiation. Electron paramagnetic resonance spectroscopy demonstrated a greater concentration of JP4-039 in mitochondria of 24 h-pelleted cells than in exponentially growing cells. These results establish a potential role of mitochondria-targeted nitroxide drugs as mitigators of radiation damage to quiescent cells including stem cells. PMID:19779106

  17. 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

  18. 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

  19. Development and dosimetry of a small animal lung irradiation platform

    PubMed Central

    McGurk, Ross; Hadley, Caroline; Jackson, Isabel L.; Vujaskovic, Zeljko

    2015-01-01

    Advances in large scale screening of medical counter measures for radiation-induced normal tissue toxicity are currently hampered by animal irradiation paradigms that are both inefficient and highly variable among institutions. Here, we introduce a novel high-throughput small animal irradiation platform for use in orthovoltage small animal irradiators. We used radiochromic film and metal oxide semiconductor field effect transistor detectors to examine several parameters, including 2D field uniformity, dose rate consistency, and shielding transmission. We posit that this setup will improve efficiency of drug screens by allowing for simultaneous, targeted irradiation of multiple animals, improving efficiency within a single institution. Additionally, we suggest that measurement of the described parameters in all centers conducting counter measure studies will improve the translatability of findings among institutions. We also investigated the use of tissue equivalent phantoms in performing dosimetry measurements for small animal irradiation experiments. Though these phantoms are commonly used in dosimetry, we recorded a significant difference in both the entrance and target tissue dose rates between euthanized rats and mice with implanted detectors and the corresponding phantom measurement. This suggests that measurements using these phantoms may not provide accurate dosimetry for in vivo experiments. Based on these measurements, we propose that this small animal irradiation platform can increase the capacity of animal studies by allowing for more efficient animal irradiation. We also suggest that researchers fully characterize the parameters of whatever radiation setup is in use in order to facilitate better comparison among institutions. PMID:23091878

  20. Procalcitonin as a predictive biomarker for total body irradiation induced bacterial load and lethality in mice

    PubMed Central

    Biju, Prabath G.; Garg, Sarita; Wang, Wenze; Choudhry, Mashkoor A.; Kovacs, Elizabeth J.; Fink, Louis M.; Hauer-Jensen, Martin

    2012-01-01

    Sepsis is the leading cause of mortality in intensive care units. Early detection and intervention are critical to prevent death. The acute radiation syndrome is characterized by damage of the gastrointestinal and hematopoietic systems. Translocation of intestinal microflora combined with immune system compromise may lead to septicemia and death. This work examined the utility of procalcitonin, a clinical sepsis biomarker, in a mouse model of radiation toxicity. C57/BL6 mice were exposed to total body irradiation (TBI). Intestinal mucosal permeability was measured in vivo, and liver bacterial load and plasma levels of procalcitonin (PCT), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP) were measured at baseline and 3.5, 7, and 10 days after TBI. The value of early PCT in predicting subsequent lethality was determined by receiver operator characteristics (ROC) analysis. Four days after TBI a dose-dependent increase in permeability of the intestinal mucosa was observed, while bacterial translocation was present from day 7 onward. There was a high positive correlation between bacterial translocation and all sepsis biomarkers, with PCT exhibiting the strongest correlation. Moreover, plasma PCT levels were elevated already from day 3.5 onwards, whereas, LPS was elevated from day 7 and LBP only 10 days after TBI. ROC analysis revealed that PCT levels measured 3.5 days after TBI predicted lethality at 10 days. These data demonstrate the value of PCT as an early biomarker in radiation-induced bacteremia for mouse studies and suggest that clinical results from other septic conditions may apply to post-radiation septicemia in humans. PMID:22576002

  1. Thrombomodulin Contributes to Gamma Tocotrienol-Mediated Lethality Protection and Hematopoietic Cell Recovery in Irradiated Mice

    PubMed Central

    Pathak, Rupak; Shao, Lijian; Ghosh, Sanchita P.; Zhou, Daohong; Boerma, Marjan; Weiler, Hartmut; Hauer-Jensen, Martin

    2015-01-01

    Systemic administration of recombinant thrombomodulin (TM) confers radiation protection partly by accelerating hematopoietic recovery. The uniquely potent radioprotector gamma tocotrienol (GT3), in addition to being a strong antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that the mechanism underlying the exceptional radioprotective properties of GT3 partly depends on the presence of endothelial TM. In vitro studies confirmed that ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy γ-irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level after 5 μM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was significantly more effective as a radioprotector in TM wild type (TM+/+) mice than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre-treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-. Thus, GT3-mediated radiation lethality protection is partly dependent on endothelial TM. Significant post-TBI recovery of hematopoietic cells, particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3-mediated lethality protection and hematopoietic recovery after exposure to TBI and may point to new strategies to enhance the efficacy of current medical countermeasures in radiological/nuclear emergencies. PMID:25860286

  2. In vivo natural antitumor resistance against murine EL-4 lymphoma cells in lethally irradiated syngeneic C57Bl/6 mice

    SciTech Connect

    Iorio, A.M.; Neri, M.; Bonmassar, E.; Titti, F.; Rossi, G.B.

    1987-08-01

    Natural resistance has been detected in lethally irradiated C57Bl/6 (B6) mice inoculated intravenously with the ascites form of a syngeneic B6 leukemia. EL-4 cells were injected into lethally irradiated (800 R) B6 mice and tumor cell proliferation was evaluated by /sup 125/IUdR uptake in different organs 4 days after the challenge. Differential growth of lymphoma cells was observed when young mice were injected as compared with older mice and when mice were treated with agents known to interfere with natural resistance (e.g., poly(I:C), FLV-P, carrageenan, cyclophosphamide, high doses of irradiated cells). Similar results were obtained by measuring rapid clearance of /sup 125/IUdR-labeled EL-4 cells from lungs of intact B6 mice. In vivo cold competition studies, employing EL-4 and several other tumor lines of the same or different haplotype, showed that only EL-4 and RBL-5 cells were capable of inhibiting syngeneic resistance against EL-4 tumor. On the contrary, YAC-1 lymphoma cells, the most susceptible target to natural killer-mediated cytotoxicity in vitro, did not compete. These results suggest that EL-4 cells express membrane determinants not detectable on normal H-2b parental bone marrow cells and are susceptible to natural resistance against hemopoietic tumor cells in lethally irradiated syngeneic B6 mice.

  3. 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

  4. 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.

  5. An explanation for the ability of cytotoxic drug pretreatment to reduce bone marrow related lethality of total body irradiation (TBI). [Mice

    SciTech Connect

    Millar, J.L.; Stephens, T.C.; Wist, E.A.

    1982-03-01

    Mice given 9 to 10 Gy total body irradiation (TBI) die a hematological death 10 to 14 days after exposure. This lethality can be avoided by pretreatment with a cytotoxic drug two days before irradiation. The best example of this is seen when 200 mg/Kg cytosine arabinoside (ara-C) is given two days before TIB. Improved survival results from an earlier onset in the recovery of marrow stem cells (CFU-s) in animals given ara-C before irradiation as compared to controls. In animals given radiation alone there is a lag phase in the recovery of CFU-s; drug pretreatment before irradiation abolishes this delay. We postulate that the cells that repopulate the CFU-s compartment after irradiation are a sub-population of the DFU-s with higher self-renewal capability, lower proliferative activity and higher radiosensitivity (D/sub 0/ = .8 Gy) than the overall population D/sub 0/ = 1.1 Gy). Further, we suggest that drug pretreatment alters the radiosensitivity of the first population, increasing it temporarily to that of the overall population. This may come about by ara-C triggering these CFU-s into a relatively radioresistant phase of the cell cycle. In the Lewis lung tumor ara-C pretreatment does not affect the response to radiation, even at times when the drug promotes the early recovery of the CFU-s. It would therefore seem that a potentially useful gain in the therapeutic index may result from these findings.

  6. 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.

  7. Specific issues in small animal dosimetry and irradiator calibration

    PubMed Central

    Yoshizumi, Terry; Brady, Samuel L.; Robbins, Mike E.; Bourland, J. Daniel

    2013-01-01

    Purpose In response to the increased risk of radiological terrorist attack, a network of Centers for Medical Countermeasures against Radiation (CMCR) has been established in the United States, focusing on evaluating animal model responses to uniform, relatively homogenous whole- or partial-body radiation exposures at relatively high dose rates. The success of such studies is dependent not only on robust animal models but on accurate and reproducible dosimetry within and across CMCR. To address this issue, the Education and Training Core of the Duke University School of Medicine CMCR organised a one-day workshop on small animal dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics and differences of cesium-137 and X-ray irradiators, methods for dose measurement, and design of experimental irradiation geometries for uniform dose distributions. This paper summarises the information presented and discussed. Conclusions Without ensuring accurate and reproducible dosimetry the development and assessment of the efficacy of putative countermeasures will not prove successful. Radiation physics support is needed, but is often the weakest link in the small animal dosimetry chain. We recommend: (i) A user training program for new irradiator users, (ii) subsequent training updates, and (iii) the establishment of a national small animal dosimetry center for all CMCR members. PMID:21961967

  8. Diabetes susceptibility of BALB/cBOM mice treated with streptozotocin. Inhibition by lethal irradiation and restoration by splenic lymphocytes

    SciTech Connect

    Paik, S.G.; Blue, M.L.; Fleischer, N.; Shin, S.

    1982-09-01

    In genetically susceptible strains of mice, repeated injections of a subdiabetogenic dose of streptozotocin induces the development of progressive insulin-dependent hyperglycemia. We showed previously that host T-cell functions play an obligatory etiologic role in this experimental disease by demonstrating that the athymic nude mouse is resistant to diabetes induction unless its T-cell functions are reconstituted by thymus graft. Here we show that lethal irradiation of euthymic (+/nu) mice of BALB/cBOM background causes selective resistance of the mice to the diabetogenic effects of the multiple low doses of streptozotocin without affecting their sensitivity to a high pharmacologic dose of the toxin. We also show that reconstitution of the irradiated mice with splenic lymphocytes causes the restoration of diabetes susceptibility. Lethally irradiated mice thus represent a useful experimental model for analyzing the host functions involved in the development of this disease. These results provide an additional support for the hypothesis that the induction of diabetes in this model system is mediated by an autoimmune amplification mechanism.

  9. A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model

    PubMed Central

    Buttigieg, Karen R.; Dowall, Stuart D.; Findlay-Wilson, Stephen; Miloszewska, Aleksandra; Rayner, Emma; Hewson, Roger; Carroll, Miles W.

    2014-01-01

    Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine. PMID:24621656

  10. Restoration of prostaglandin releasing macrophage populations in lethally irradiated mice with spleen cells from bone marrow-depleted donors

    SciTech Connect

    Shibata, Y.; Volkman, A. )

    1991-04-01

    Previous studies in mice severely depleted of bone marrow cells by 89Sr showed persistent monocytopenia and impaired expression of prostaglandin E2-releasing splenic macrophages (PGSM) despite the occurrence in the spleen of more than 10-fold increases in pluripotential stem cells and M phi colony-forming cells. To determine whether the observed deficits were due to a lack of precursors of blood monocytes and PGSM in the spleens of 89Sr-treated mice, radiation chimeras were established by i.v. infusion of 2 x 10(6) spleen cells from 89Sr donor CBA/J or semisyngeneic B6CB F1 hybrid mice into lethally gamma-irradiated CBA/J recipients. Blood monocyte levels were greater than normal by day 14 and PGSM induced by Corynebacterium parvum were demonstrated by day 28. These restored M phi populations expressed the donor haplotype detected in vitro with haplotype-specific monoclonal anti-H-2K plus complement. 89Sr treatment of the chimeras resulted in profound depletion of monocytes and PGSM. The data indicate that the spleen of the 89Sr-treated mouse, which is an ineffective source of circulating monocytes and PGSM, contains cells which can generate both of these populations following infusion into lethally irradiated recipients. Since the bone marrow of such recipients was capable of being repopulated, the aggregate observations suggest that functional bone marrow is obligatory for the generation of blood monocytes and PGSM populations.

  11. 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

  12. 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

  13. T-cell differentation in lethally irradiated and reconstituted mice: functional recovery of PNA-fractionated subpopulations. [X ray

    SciTech Connect

    Kraal, G.; Groeneveld, P.H.P.; Boden, D.; Kors, N.

    1981-07-15

    In mammals T lymphocytes are generated in the thymus from hemopoietic precursor cells. The thymus is able to instruct the T cells during their differentiation resulting in functionally different subpopulations which can leave the thymus for the peripheral lymphoid organs. These functionally different T-cell subpopulations have been described using the alloantigens Ly-1, 2, and 3. Another probe to study thymus subpopulations is the use of the nonmitogenic lectin peanut agglutinin (PNA). After lethal irradiation and reconsitution (IR) there is a 6-day lag before thymus cells start to proliferate. In the first 6 days there is a relative enrichment of PNA-negative cells, which are Ly-1/sup +/ and radioresistant. After IR the mitogenic responses of the PNA-negative cells recover earlier than those of the PNA-positive cells; the implications of this finding for different T-cell lineages are discussed.

  14. 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

  15. [Clinical and experimental parallels between immunological observations of irradiated animals and patients injured during Chernobyl accident].

    PubMed

    Mal'tsev, V N

    2011-01-01

    Immunological parameters in different periods of acute radiation syndrome (ARS) of experimental animals and Chernobyl reactor accident-injured patients have been studied. 148 patients and experimental animals (123 dogs and 198 monkeys) were observed after radiation exposure of different levels (from a sub-lethal dose to the minimal absolute lethal dose). We have found the increase in the C-reactive protein, fluctuation of normal antibody titers and the complement in blood serum, as well as the growing number of skin microbes after exposures to lethal doses. Experimental results match clinical data in terms of ARS progress phases but differ from the latter in terms of the time of clinical manifestations. The highest rate of clinical manifestations is observed on the 7-14 days for experimental animals (rats, dogs and monkeys) and on the 20-30 days for patients after radiation exposure. Regenerative processes in animals run faster than those in humans. PMID:22279769

  16. 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.

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

    PubMed Central

    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.

    2009-01-01

    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 μM) 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. PMID:19303399

  18. 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.

  19. Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice: dosage and the window of time

    PubMed Central

    Kovalenko, Olga A.; Azzam, Edouard I.; Ende, Norman

    2013-01-01

    The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27–30 weeks old) were exposed to an absorbed dose of 9–10 Gy of 137Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 108 or 2 × 108 HUCB mononucleated cells at 24–52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 108 HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24–52 h after exposure. PMID:23792493

  20. 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

    2016-01-01

    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. PMID:27196884

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

    PubMed

    Pietzner, J; Merscher, B M; Baer, P C; Duecker, R P; Eickmeier, O; Fußbroich, D; Bader, P; Del Turco, D; Henschler, R; Zielen, S; Schubert, R

    2016-04-01

    Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model. PMID:26752140

  7. The evaluation of 6 and 18 MeV electron beams for small animal irradiation

    NASA Astrophysics Data System (ADS)

    Chao, T. C.; Chen, A. M.; Tu, S. J.; Tung, C. J.; Hong, J. H.; Lee, C. C.

    2009-10-01

    A small animal irradiator is critical for providing optimal radiation dose distributions for pre-clinical animal studies. This paper focuses on the evaluation of using 6 or 18 MeV electron beams as small animal irradiators. Compared with all other prototypes which use photons to irradiate small animals, an electron irradiator has many advantages in its shallow dose distribution. Two major approaches including simulation and measurement were used to evaluate the feasibility of applying electron beams in animal irradiation. These simulations and measurements were taken in three different fields (a 6 cm × 6 cm square field, and 4 mm and 30 mm diameter circular fields) and with two different energies (6 MeV and 18 MeV). A PTW Semiflex chamber in a PTW-MP3 water tank, a PTW Markus chamber type 23343, a PTW diamond detector type 60003 and KODAK XV films were used to measure PDDs, lateral beam profiles and output factors for either optimizing parameters of Monte Carlo simulation or to verify Monte Carlo simulation in small fields. Results show good agreement for comparisons of percentage depth doses (<=2.5% for 6 MeV e; <=1.8% for 18 MeV e) and profiles (FWHM <= 0.5 mm) between simulations and measurements on the 6 cm field. Greater deviation can be observed in the 4 mm field, which is mainly caused by the partial volume effects of the detectors. The FWHM of the profiles for the 18 MeV electron beam is 32.6 mm in the 30 mm field, and 4.7 mm in the 4 mm field at d90. It will take 1-13 min to complete one irradiation of 5-10 Gy. In addition, two different digital phantoms were also constructed, including a homogeneous cylindrical water phantom and a CT-based heterogeneous mouse phantom, and were implemented into Monte Carlo to simulate dose distribution with different electron irradiations.

  8. 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

  9. 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

  10. Effect of gamma-ray irradiation on the unloaded animal model

    NASA Astrophysics Data System (ADS)

    Choi, Jong-Il; Yoon, Min-Chul; Sung, Nak-Yoon; Kim, Jae-Hun; Jong Lee, Yun; Lee, Ki-Soo; Choi, In-Ho; Nam, Gung Uk; Lee, Ju-Woon

    During the space flight, human beings encountered the extreme conditions such as the cosmic ray irradiation and microgravity. There have been developed the animal models to simulate the microgravity condition in laboratory, but no study was carried out to investigate the combined effect of microgravity and exposure to irradiation. In this study, it was examined the effect of gamma irradiation on the suspension model. Rats were divided into four groups, Group I was loaded and not exposed to gamma irradiation, Group 2 was unloaded and not exposed, Group 3 was loaded and exposed to gamma irradiation at the dose of 50 mSV, and Group 4 was unloaded and exposed to gamma irradiation at the same dose. It was measured body, muscles and tissues weights and the biological analysis and the hematological response in blood samples were conducted. Anti-gravity tissue weight was only changed between loading and un-loading condition. However, there was no difference between irradiation exposed and not exposed unloaded groups. To know the difference of protein expression in anti-gravity tissues, 2 dimensional electrophoresis was performed. It has been found that the expression levels of several proteins were different by unloading condition and by irradiation exposed condition, respectively. These results provided the information on the combined effect of irradiation and microgravity to simulate space flight, and could be useful to search the candidate material for the countermeasure against space environment.

  11. 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.

  12. 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.

  13. Changes of rheologic properties of blood in experimental animals irradiated with low-energy lasers

    NASA Astrophysics Data System (ADS)

    Turczynski, Boleslaw; Cieslar, Grzegorz; Sieron, Aleksander; Adamek, Mariusz

    1995-03-01

    The effect of infrared laser radiation on viscosity of serum and blood in experimental animals was investigated. The experiment was carried out on 30 male guinea pigs weighing 280 - 320 g. Fifteen animals composed a group irradiated with laser, the other 15 animals made up a control group in which no irradiation was made. A semiconductive laser generating infrared radiation (wavelength -- 904 nm, frequency -- 800 Hz, pulse duration -- 200 ns, mean power - - 8.7 mW) was used. The right infracostal region of the animal was irradiated 3 minutes daily for 15 consecutive days. After the end of the experiment in the obtained blood and serum the measurement of hematocrit and rheologic examination was made in the temperature of 310 K. The estimation of viscosity of whole blood was made by means of low-gradient viscosimeter `low shear,' for shearing velocities: D1 equals 0.116 s-1 and D2 equals 4.59 s-1. The viscosity of serum was estimated using Ubbelohd's microviscosimeter. A significant increase of whole blood viscosity measured for shearing velocity D1 was obtained in irradiated animals as compared to the controls. No statistically significant differences in viscosity of whole blood at clotting speed D2, viscosity of serum and hematocrit were observed between both groups of animals. The obtained data prove a distinct effect of low-energy laser radiation on rheologic properties of blood in experimental animals. The increase of whole blood viscosity, observed only at low shearing velocities, is probably related to the changes of structural and functional properties of cell membranes of erythrocytes resulting in a decrease of aggregation.

  14. Space microbiology--lethality, mutagenicity and cytological effects of terrestrial microorganisms by irradiation of cosmic proton under simulated space condition.

    PubMed

    Koike, J; Taguchi, H

    1993-04-01

    We have been discussing in connection with a space quarantine. The subject is not merely an academic problem, but it contains a fundamental problem which avoid the contamination of other planets by terrestrial microflora. The space environments in the solar system were simulated by using an apparatus of cryostat (low temperature of 110-310K, high vacuum of 1 x 10(-8) torr) and proton irradiation from the Van de Graaff generator. After exposure to a barrage of protons corresponding to about 250 years in solar space, Tobacco mosaic virus, Bacillus subtilis spore, Staphylococcus aureus. Micrococcusflavus, Clostridium mangenoti spore and Aspergillus niger spore showed considerably high survival rates. Furthermore, it was found firstly that an irradiation of proton induced considerable mutation frequency compared to that of spontaneous and caused also the cytological effects based on a damage of chromosome. PMID:7967372

  15. Degeneration and atrophy of the thymus of lethally irradiated dogs, rescued by transfusion of cryopreserved autologous blood leukocytes

    SciTech Connect

    Calvo, W.; Fliedner, T.M.; Herbst, E.W.; Huegl, E.B.; Boedey, B.

    1987-12-01

    Dogs exposed to a fatal radiation dose of 12 Gy were rescued by transfusion of autologous blood leukocytes. A severe acute and long-lasting damage to the thymus was observed. The acute damage, as observed on the tenth day, consisted of a marked reduction in the number of lymphocytes, degeneration of Hassall's bodies, and hemorrhage. Long-term effects, observed several months after irradiation, were partial to total atrophy of the thymus. Regeneration, when it occurred, was limited to a few small isolated areas in which lymphopoiesis was supported by epithelial reticular cells. In contrast, the lymph nodes of all dogs had abundant cortical lymphopoiesis. The abundant hemopoiesis present in the marrow from the tenth day after irradiation until the end of the observation period should have provided sufficient circulating precursor cells to seed the thymus and regenerate the organ to the same extent as that observed in the other blood-forming organs. The impairment of lymphopoietic regeneration in the thymus seems to be due, therefore, to damage caused by irradiation on the specific stroma of the organ, which is not able to support such activity.

  16. 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

  17. 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.

  18. Design and characterization of an economical 192Ir hemi-brain small animal irradiator

    PubMed Central

    Sio, Terence T.; Beltran, Chris J.; Tryggestad, Erik J.; Gupta, Shiv K.; Blackwell, Charles R.; McCollough, Kevin P.; Sarkaria, Jann N.; Furutani, Keith M.

    2015-01-01

    Purpose To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Materials and methods A high dose rate (HDR) 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements. Results The tungsten collimator provided 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, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients. PMID:24844370

  19. 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. PMID:27008208

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    PubMed

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia. PMID:20558844

  6. Effect of laser irradiation for healing of the skin-muscle wounds of animals

    NASA Astrophysics Data System (ADS)

    Lapina, Victoria A.; Veremei, Eduard I.; Pancovets, Evgeniy A.

    2000-05-01

    The purpose of our investigation was to study the medical effect of low-intensity laser influence on healing of skin- muscle wounds of agricultural animals. We used the laser radiation of low intensity for cub's therapy: to sucking-pigs after herniotomy and castration, to cattle cubs after skin- muscle wounds. The animals were kept under clinical observation up to their recovery. The recuperation dynamic was observed by changing of blood quotients, leukograms, sizes of inflammatory edema, general behavior of animals. The positive dynamic of blood quotients of the experimental animal groups was really higher than that in control. The analysis of wound healing after laser influence shows that wound surface of experimental group was to a great extent smaller in comparison with control group of animals. So, these facts testify about anti-inflammatory action of laser radiation, which hastens regenerative and rehabilitative processes. Analysis of the obtained experimental data has revealed the positive influence of laser irradiation on the dynamics of wound adhesion of agricultural animals.

  7. 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.

  8. An x-ray image guidance system for small animal stereotactic irradiation

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

    An x-ray image-guided small animal stereotactic irradiator was developed and characterized to enable tumor visualization and accurate target localization for small field, high dose irradiation. The system utilizes a custom collimation system, a motorized positioning system (x, y, θ), a digital imaging panel and operating software, and is integrated with a commercial x-ray unit. The essential characteristics of the irradiator include small radiation fields (1-10 mm), high dose rate (>10 Gy min-1) and submillimeter target localization. The software enables computer-controlled image acquisition, stage motion and target localization providing simple and precise automated target localization. The imaging panel was characterized in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution. Overall localization accuracy and precision were assessed. SNR, CNR and spatial resolution are 24 dB, 21 dB and 2.8 lp mm-1, respectively, and localization accuracy is approximately 65 µm with 6 µm precision. With the aid of image guidance, system performance was subsequently used to evaluate radiation response in a rat orthotopic lung tumor effectively sparing normal tissues and in a mouse normal lung. The capabilities of 3D treatment and cone-beam computed tomography are presented for 3D localization and delivery as a work in progress.

  9. An x-ray image guidance system for small animal stereotactic irradiation.

    PubMed

    Song, K H; Pidikiti, R; Stojadinovic, S; Speiser, M; Seliounine, S; Saha, D; Solberg, T D

    2010-12-01

    An x-ray image-guided small animal stereotactic irradiator was developed and characterized to enable tumor visualization and accurate target localization for small field, high dose irradiation. The system utilizes a custom collimation system, a motorized positioning system (x, y, θ), a digital imaging panel and operating software, and is integrated with a commercial x-ray unit. The essential characteristics of the irradiator include small radiation fields (1-10 mm), high dose rate (>10 Gy min(-1)) and submillimeter target localization. The software enables computer-controlled image acquisition, stage motion and target localization providing simple and precise automated target localization. The imaging panel was characterized in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution. Overall localization accuracy and precision were assessed. SNR, CNR and spatial resolution are 24 dB, 21 dB and 2.8 lp mm(-1), respectively, and localization accuracy is approximately 65 µm with 6 µm precision. With the aid of image guidance, system performance was subsequently used to evaluate radiation response in a rat orthotopic lung tumor effectively sparing normal tissues and in a mouse normal lung. The capabilities of 3D treatment and cone-beam computed tomography are presented for 3D localization and delivery as a work in progress. PMID:21081818

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

    PubMed Central

    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.

    2008-01-01

    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° and 270° microRT treatment positions and (2) a hemispheric (left-brain) irradiation comprised of a single A-P vertex beam at the 0° 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 immobilizer added ±0.1 mm to

  11. 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

  12. 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

    ... (78 FR 27303). That document used incorrect style for the strength units describing radiation sources... Register of May 10, 2013 (78 FR 27303). That document used incorrect style for the strength units..., and Handling of Animal Feed and Pet Food; Electron Beam and X-Ray Sources for Irradiation of...

  13. 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.

  14. Adaptation, Commissioning, and Evaluation of a 3D Treatment Planning System for High-Resolution Small-Animal Irradiation.

    PubMed

    Jeong, Jeho; Chen, Qing; Febo, Robert; Yang, Jie; Pham, Hai; Xiong, Jian-Ping; Zanzonico, Pat B; Deasy, Joseph O; Humm, John L; Mageras, Gig S

    2016-06-01

    Although spatially precise systems are now available for small-animal irradiations, there are currently limited software tools available for treatment planning for such irradiations. We report on the adaptation, commissioning, and evaluation of a 3-dimensional treatment planning system for use with a small-animal irradiation system. The 225-kV X-ray beam of the X-RAD 225Cx microirradiator (Precision X-Ray) was commissioned using both ion-chamber and radiochromic film for 10 different collimators ranging in field size from 1 mm in diameter to 40 × 40 mm(2) A clinical 3-dimensional treatment planning system (Metropolis) developed at our institution was adapted to small-animal irradiation by making it compatible with the dimensions of mice and rats, modeling the microirradiator beam orientations and collimators, and incorporating the measured beam data for dose calculation. Dose calculations in Metropolis were verified by comparison with measurements in phantoms. Treatment plans for irradiation of a tumor-bearing mouse were generated with both the Metropolis and the vendor-supplied software. The calculated beam-on times and the plan evaluation tools were compared. The dose rate at the central axis ranges from 74 to 365 cGy/min depending on the collimator size. Doses calculated with Metropolis agreed with phantom measurements within 3% for all collimators. The beam-on times calculated by Metropolis and the vendor-supplied software agreed within 1% at the isocenter. The modified 3-dimensional treatment planning system provides better visualization of the relationship between the X-ray beams and the small-animal anatomy as well as more complete dosimetric information on target tissues and organs at risk. It thereby enhances the potential of image-guided microirradiator systems for evaluation of dose-response relationships and for preclinical experimentation generally. PMID:25948321

  15. 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…

  16. 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.

  17. [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

  18. 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)

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 16,16-Dimethyl prostaglandin E2 and/or syngeneic bone marrow transplantation increase mouse survival after supra-lethal total body irradiation

    SciTech Connect

    Berk, L.B.; Patrene, K.D.; Boggs, S.S. )

    1990-06-01

    We evaluated the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2), with and without syngeneic bone marrow transplantation (BMT) on the survival and hematopoietic recovery of mice given 14-20 Gy total body irradiation (TBI). Survival of mice given combined dm-PGE2 and BMT was improved significantly over that of mice given either treatment alone. The 30-day survival after 14, 15, 16 or 18 Gy TBI for combined treatment was 97, 90, 20 or 10 percent, respectively. The corresponding 30-day survival rates for mice given BMT alone were 69, 60, 7 or 0 percent, respectively. For dm-PGE2 alone, 30-day survival was 63, 20, 10 or 0 percent, respectively. Deaths in both dm-PGE2 treated groups generally occurred after day 10 whereas deaths in the BMT group occurred before day 10. All irradiated controls were dead on or before day 10; after larger doses, deaths clustered around day 5. After 20 Gy TBI, all mice in all groups were dead by day 7. Studies of white blood cell recovery 1-9 days after 14 Gy TBI showed improvement with BMT, whereas dm-PGE2 did not enhance recovery. Nucleated cells per humerus, spleen weight, and spleen iron uptake (erythropoiesis) were also improved by BMT but not dm-PGE2.

  4. Irradiated Cerastes cerastes venom as a novel tool for immunotherapy.

    PubMed

    Oussedik-Oumehdi, Habiba; Laraba-Djebari, Fatima

    2008-01-01

    Immunotherapy is the most effective treatment for the snake bites. The antivenoms are commonly obtained by hyperimmunization of animals that suffer from venom toxicity. The present report describes gamma irradiation effects on Cerastes cerastes venom. Doses of 1 kGy and 2 kGy gamma radiations were used for venom detoxification. These treated venoms did not have any residual lethal effects until 10 LD(50). Immunological analysis of sera raised against native and irradiated venoms, showed that elicited antibodies to irradiated venoms were able to recognize native venom. Anti-2 kGy irradiated venom had more protective ability than anti-native venom, as tested in mice. PMID:18306103

  5. Dosimetric variation due to the photon beam energy in the small-animal irradiation: A Monte Carlo study

    SciTech Connect

    Chow, James C. L.; Leung, Michael K. K.; Lindsay, Patricia E.; Jaffray, David A.

    2010-10-15

    Purpose: The impact of photon beam energy and tissue heterogeneities on dose distributions and dosimetric characteristics such as point dose, mean dose, and maximum dose was investigated in the context of small-animal irradiation using Monte Carlo simulations based on the EGSnrc code. Methods: Three Monte Carlo mouse phantoms, namely, heterogeneous, homogeneous, and bone homogeneous were generated based on the same mouse computed tomography image set. These phantoms were generated by overriding the tissue type of none of the voxels (heterogeneous), all voxels (homogeneous), and only the bone voxels (bone homogeneous) to that of soft tissue. Phase space files of the 100 and 225 kVp photon beams based on a small-animal irradiator (XRad225Cx, Precision X-Ray Inc., North Branford, CT) were generated using BEAMnrc. A 360 deg. photon arc was simulated and three-dimensional (3D) dose calculations were carried out using the DOSXYZnrc code through DOSCTP in the above three phantoms. For comparison, the 3D dose distributions, dose profiles, mean, maximum, and point doses at different locations such as the isocenter, lung, rib, and spine were determined in the three phantoms. Results: The dose gradient resulting from the 225 kVp arc was found to be steeper than for the 100 kVp arc. The mean dose was found to be 1.29 and 1.14 times higher for the heterogeneous phantom when compared to the mean dose in the homogeneous phantom using the 100 and 225 kVp photon arcs, respectively. The bone doses (rib and spine) in the heterogeneous mouse phantom were about five (100 kVp) and three (225 kVp) times higher when compared to the homogeneous phantom. However, the lung dose did not vary significantly between the heterogeneous, homogeneous, and bone homogeneous phantom for the 225 kVp compared to the 100 kVp photon beams. Conclusions: A significant bone dose enhancement was found when the 100 and 225 kVp photon beams were used in small-animal irradiation. This dosimetric effect, due to

  6. 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.

  7. 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.

  8. Apparent lethal concentrations of pyrolysis products of some polymeric materials

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Marcussen, W. H.; Furst, A.; Kourtides, D. A.; Parker, J. A.

    1976-01-01

    Thirty-nine samples of polymeric materials were evaluated to determine the apparent lethal concentrations of their pyrolysis products. The materials were compared on the basis of the apparent lethal concentration for 50 percent of the test animals. Relative toxicity rankings based o apparent lethal concentration values can differ significantly depending on whether they are based on weight of sample charged or weight of sample pyrolyzed. The ranking of polyphenylene sulfide is particularly sensitive to this difference.

  9. Lethal and Sub-lethal Effects of UVB on Juvenile Biomphalaria glabrata (Mollusca: Pulmonata)

    PubMed Central

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

    2007-01-01

    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 (290–320 nm) 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

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

    PubMed Central

    Lucero, Steven; Monjazeb, Arta M; Li, Jian Jian

    2015-01-01

    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. PMID:26180678

  11. Dosimetric impact of monoenergetic photon beams in the small-animal irradiation with inhomogeneities: A Monte Carlo evaluation

    NASA Astrophysics Data System (ADS)

    Chow, James C. L.

    2013-05-01

    This study investigated the variations of the dose and dose distribution in a small-animal irradiation due to the photon beam energy and presence of inhomogeneity. Based on the same mouse computed tomography image set, three Monte Carlo phantoms namely, inhomogeneous, homogeneous and bone-tissue phantoms were used in this study. These phantoms were generated by overriding the relative electron density of no voxel (inhomogeneous), all voxel (homogeneous) and the bone voxel (bone-tissue) to one. 360° photon arcs with beam energies of 50-1250 kV were used in mouse irradiations. Doses in the above phantoms were calculated using the EGSnrc-based DOSXYZnrc code through the DOSCTP. It was found that the dose conformity increased with the increase of the photon beam energy from the kV to MV range. For the inhomogeneous mouse phantom, increasing the photon beam energy from 50 kV to 1250 kV increased about 21 times the dose deposited at the isocenter. For the bone dose enhancement, the mean dose was 1.4 times higher when the bone inhomogeneity was not neglected using the 50 kV photon beams in the mouse irradiation. Bone dose enhancement affecting the mean dose in the mouse irradiation can be found in the photon beams with energy range of 50-200 kV, and the dose enhancement decreases with an increase of the beam energy. Moreover, the MV photon beam has a higher dose at the isocenter, and a better dose conformity compared to the kV beam.

  12. 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.

  13. 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

  14. [Structural and physicochemical characteristics of DNA from animal tissue subjected to chronic irradiation in the Chernobyl area].

    PubMed

    Blagoĭ, Iu P; Kornilova, S V; Leont'ev, V S; Sorokin, V A; Gladchenko, G O; Valeev, V A; Grigor'ev, D N; Kapinos, L E; Bondarenko, V N; Kolod, V Ia

    1994-01-01

    The properties of animal DNAs exposed to prolonged irradiation in the Chernobyl zone, have been studied by the methods of viscometry, thermal denaturation, IR-spectroscopy, and electrophoresis. High content of low-molecular fractions have been observed in the preparations of DNA from liver and spleen, their quantities increasing with age and generation of animals. This effect is especially strong in DNA from liver. Low-molecular fraction of DNA is shown to be enriched with G-C pairs and to consist of the following four fractions: 1) approximately 500 base pairs (B.p.), 2) approximately 1.5 divided by 2 thousand B.p., 3) approximately 4 divided by 5 thousand B.p. and 4) a mixture of approximately 20 thousand B.p. fragments. Further, it has been observed that the DNA preparations from the tissues of experimental animals contain about ten times higher contents of Fe, Zn, Se and other elements as compared to the control preparations. PMID:7981273

  15. Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies.

    PubMed

    Niwa, Ohtsura

    2003-10-13

    Many studies confirmed that radiation induces genomic instability in whole-body systems. However, the results of the studies are not always consistent with each other. Attempts are made in the present review to resolve the discrepancies. Many of the studies in human and experimental animals utilize the length change mutation of minisatellite sequences as a marker of genomic instability. Minisatellite sequences frequently change their length, and the data obtained by conventional Southern blotting give rather qualitative information, which is sometimes difficult to scrutinize quantitatively. This is the problem inevitably associated with the study of minisatellite mutations and the source of some conflicts among studies in humans and mice. Radiation induction of genomic instability has also been assessed in whole-body experimental systems, using other markers such as the mouse pink-eyed unstable allele and the specific pigmentation loci of medaka fish (Oryzias latipes). Even though there are some contradictions, all these studies have demonstrated that genomic instability is induced in the germ cells of irradiated parents, especially of males, and in offspring born to them. Among these, transmission of genomic instability to the second generation of irradiated parents is limited to the mouse minisatellite system, and awaits further clarification in other experimental systems. PMID:14557813

  16. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-07-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

    Fitch, F. Morán; García-Garduño, O. A.; Martínez-Dávalos, A.

    2010-12-01

    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.

  19. 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.

  20. 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

  1. A Preliminary Study of the Application of a Model Animal-Caenorhabidity elegans' Exposure to a Low-Energy Ion Irradiation System

    NASA Astrophysics Data System (ADS)

    Liu, Xuelan; Cai, Kezhou; Feng, Huiyun; Xu, An; Yuan, Hang; Yu, Zengliang

    2007-10-01

    Because of the lack of suitable animal models adapted to high vacuum stress in the low-energy ion implantation system, the bio-effects ion irradiation with an energy less than 50 keV on multi-cellular animal individuals have never been investigated so far. The nematode Caenorhabditis elegans has proved to be an excellent animal model used for the study of a broad spectrum of biological issues. The purpose of this work was to investigate the viability of this animal under ion irradiation. We studied the protection effects of glycerol and trehalose on the enhancement of nematodes' ability to bear the vacuum stress. The results showed that the survival of the nematodes was enhanced remarkably under long and slow desiccation, even without glycerol and trehalose. 15% glycerol showed a better anti-vacuum stress effect on the nematodes than trehalose did under short-time desiccation. Low-temperature pre-treatment or post-treatment of the samples had no obvious effect on the survival scored after argon ion irradiation. Moreover, little effect was induced by 15% glycerol- and vacuum-exposure on germ cell apoptosis, compared to the untreated control sample. It issuggested that such treatment would provide relatively low background for genotoxic evaluations with ion irradiation.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Irradiation of prolate spheroidal models of humans and animals in the near field of a small loop antenna

    NASA Astrophysics Data System (ADS)

    Lakhtakia, A.; Iskander, M. F.; Durney, C. H.; Massoudi, H.

    1982-01-01

    Analysis of the near-field irradiation of prolate spheroidal models of humans and animals by a small coaxial loop antenna is described. The near fields of the antenna are known exactly and hence are used to identify the suitable field parameters involved in the near-field absorption in the spheroidal model. An integral equation is formulated in terms of the transverse dyadic Green's function, and the fields radiated by the current loop are expanded in terms of the vector spherical harmonics. The extended boundary condition method is then employed to solve the integral equation. The power distribution and the average specific absorption rate (SAR) are calculated and plotted, for different human and animal models, as a function of the separation distance from the loop. It is shown that for distances less than 5λ the average SAR values oscillate about the far-field value. In particular, for d/λ < 0.4 an increase in the average SAR values was generally observed. It is also shown that in spite of the complicated nature of the near fields the absorption characteristics can still be explained in terms of the incident radiation. Furthermore, from the calculated SAR distributions at different frequencies it is shown that at all frequencies, excessive heating occurs at the surface of the spheroid while a limited absorption occurs in the central region around the major axis. This result is of particular importance in hyperthermia, where extensive efforts are being directed toward achieving deep-tissue heating by a coaxial coil carrying RF power at about 27 MHz.

  8. 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

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

    PubMed

    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. Lethal Injection for Execution: Chemical Asphyxiation?

    PubMed Central

    Zimmers, Teresa A; Sheldon, Jonathan; Lubarsky, David A; López-Muñoz, Francisco; Waterman, Linda; Weisman, Richard; Koniaris, Leonidas G

    2007-01-01

    Background Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended. Methods and Findings We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest. Conclusions We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable. PMID:17455994

  11. 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.

  12. Increasing the reliability of the GUB-20.000 {gamma}-apparatus for irradiation of large laboratory animals

    SciTech Connect

    Videnskii, V.G.

    1995-03-01

    Experimental results are briefly presented for the strength of ultrastrong high modulus POLYMER SVM fiber cables as a function of the gamma irradiation dose. The lines were placed in water and irradiated to model the operation of the GUB-20.000 apparatus. The fibers exhibited elastic deformation followed by a section of plastic flow, during which the samples stretched by 20%. The strength of fiber line, within the dose limits used, did not depend on the irradiation dose. Therefore, the lines can be used to upgrade the gamma irradiation apparatus currently using Capron fishing line. 5 refs., 1 tab.

  13. 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

    .... Background In a notice published in the Federal Register of February 29, 2012 (77 FR 12226), FDA announced... 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...

  14. The Lethality Test System

    NASA Astrophysics Data System (ADS)

    Parsons, W. M.; Sims, J. R.; Parker, J. V.

    1986-11-01

    The Lethality Test System (LTS) under construction at Los Alamos is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/sec. The launcher is a 25 mm round bore, plasma armature railgun 22 m in length. Preinjection is accomplished with a two-stage light gas gun capable of 7 km/sec. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92 percent of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1-1.3 MA ramped current waveform will be delivered to the railgun.

  15. Lethality test system

    SciTech Connect

    Parsons, W.M.; Sims, J.R.; Parker, J.V.

    1986-01-01

    The Lethality Test System (LTS), presently under construction at Los Alamos, is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/s. The launcher is a 25 mm round bore, plasma armature railgun extending 22 m in length. Preinjection is accomplished with a two-stage gas gun capable of 7 km/s. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92% of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1 MA to 1.3 MA ramped current waveform will be delivered to the railgun.

  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. Radiobiological speculations on therapeutic total body irradiation

    SciTech Connect

    Vriesendorp, H.M. )

    1990-01-01

    Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references.

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

    PubMed

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

    2016-08-15

    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

  19. 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

  20. 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...

  1. The use of postoperative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: An animal model

    SciTech Connect

    Konski, A.; Weiss, C.; Rosier, R.; Poulter, C.; Pelligrini, V.; Anthony, P.; Evarts, C.M.; Richardson, M.; Henzler, M.; Rubin, P. )

    1990-04-01

    Radiation has been shown to be effective in the prevention of heterotopic bone. The exact etiology of heterotopic bone is unknown. Total hip prosthetic devices that do not depend upon bone cement for fixation have become increasingly popular. The mechanism by which the bone forms around the prosthesis is similar to the process by which fractures heal which has been shown to be sensitive to irradiation. Using a rabbit model we have undertaken a study to investigate the effect of irradiation on the bony ingrowth on porous coated implants. Forty-five rabbits had porous coated implants surgically placed in the tibiae bilaterally. Each rabbit had one tibia randomly irradiated with 1,000 cGy in 5 fractions starting on the first post-operative day. Animals were sacrificed weekly starting 2 weeks post-operatively and the tibae were sent for pullout studies. The amount of force necessary to pullout the treated tibae was statistically less than the amount of force necessary to remove the untreated tibae at 2 weeks. From 3 weeks on there was no difference in the force necessary to remove the prosthesis from the untreated or treated tibae. Histologically, the untreated tibae showed bone formation while the treated tibae did not. Because of these results, it is suggested that the treatment of patients at risk for development of heterotopic bone be modified to only include the area between the femur and pelvis avoiding treatment of the prosthetic device.

  2. Failure of rats to escape from a potentially lethal microwave field

    SciTech Connect

    Carroll, D.R.; Levinson, D.M.; Justesen, D.R.; Clarke, R.L.

    1980-01-01

    Ocularly pigmented rats, all mature females of the Long-Evans strain, were repeatedly presented an opportunity to escape from an intense 918-MHz field (whole-body dose rate . 60 mW/g) to a field of lower intensity (40, 30, 20, or 2 mW/g) by performing a simple locomotor response. Other rats could escape 800-microamperemeter faradic shock to the feet and tail by performing the same response in the same milieu, a multimode cavity. None of 20 irradiated rats learned to associate entry into a visually well-demarcated area of the cavity with immediate reduction of dose rate, in spite of field-induced elevations of body temperature to levels that exceeded 41 degrees C and would have been lethal but for a limit on durations of irradiation. In contrast, all of ten rats motivated by faradic shock rapidly learned to escape. The failure of escape learning by irradiated animals probably arose from deficiencies of motivation and, especially, sensory feedback. Whole-body hyperthermia induced by a multipath field may lack the painful or directional sensory properties that optimally promote the motive to escape. Moreover, a decline of body temperature after an escape-response-contingent reduction of field strength will be relatively slow because of the large thermal time constants of mammalian tissues. Without timely sensory feedback, which is an essential element of negative reinforcement, stimulus-response associability would be imparied, which could retard or preclude learning of an escape response.

  3. Definition of lethality thresholds for KE less-lethal projectiles

    NASA Astrophysics Data System (ADS)

    Cuadros, Jaime H.

    1997-01-01

    The interest in the definition and application of the lethality threshold for KE less-lethal projectiles has increased in the last few years, as the demand for proper use of these weapons has increased from the public at large and the law enforcement community. Experiments have been performed and reported utilizing commercially available projectiles in 12 ga., 37 mm against an anthropomorphic dummy and damage criteria developed by the automobile industry. The utility of the method is discussed and future trends are presented.

  4. Tityus serrulatus venom--A lethal cocktail.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). PMID:26522893

  5. 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.

  6. [Indralin--a novel effective radioprotector during irradiation by high-energy protons].

    PubMed

    Shashkov, V S; Efimov, V I; Vasin, M V; Antipov, V V; Iliukhin, A V; Vlasov, P A; Karsanova, S K; Grigor'ev, Iu G; Ushakov, I B

    2010-01-01

    Experiments with 120 mongrel dogs were aimed at the assessment of radio protective strength of indralin and local shielding of the pelvic marrow from 2.5 Gy, and also their concurrent use for the dogs irradiated by protons (240 MeV) at absolutely lethal and over-lethal 4 Gy and 5 Gy. Clinical observations, hematological investigations and ECG analysis of survived animals were conducted 4.5 years post the irradiation. Dogs that remained healthy following 3.5 to 4.5 years since the irradiation were sacrificed for pathomorphological investigations. The radioprotective effect of local shielding against 4 Gy was weak while this effect of intramuscular indralin (10, 20, 40 mg/kg of body) was significant reaching 50 to 67.7%. The concurrent use of two methods had, apparently, potentiated the 100% radioprotection of the animals irradiated by overlethal 5 Gy. Blood investigations of the survived dogs every 2-4 months evidenced that complete recovery of the total leukocyte count had taken 9 to 13 months. Also, dogs' pregnancy in 9-10 months since the beginning of irradiation pointed to maintenance of fertility and the ability to parturiate 2 or 3 times yielding 5-6 live cubs. Necropsy of the dogs did not reveal gross macroscopic structural changes of visceral organs or tissues. Seven out of 27 sacrificed dogs had benign tumors infrequent in intact dogs at this age. PMID:20803992

  7. 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

  8. 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

  9. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    SciTech Connect

    Isildar, M.; Bakale, G.

    1983-01-01

    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 ..gamma..-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains. (ACR)

  10. Rescue of fish exposed to a lethal dose of pathogen, by signals from sublethally exposed survivors.

    PubMed

    Mothersill, Carmel; Austin, Dawn; Fernandez-Palomo, Cristian; Seymour, Colin; Auchinachie, Niall; Austin, Brian

    2015-03-01

    Rainbow trout (Oncorhynchus mykiss, Walbaum) were challenged intraperitoneally with a sublethal dose of Vibrio anguillarum VIB1 and allowed to recover. Then, after 7 days, naïve fish, (designated as 'bystander' fish) which had never been exposed to the pathogen, were introduced to the same tank. These swam with the adapted (recovered) fish for 7 days before both groups and a control (never exposed directly to the pathogen or to recovered fish) group were exposed to a lethal dose of VIB1. Mortality records were 100% in the control group within 3 days, 47% in the adapted group and 60% in the unchallenged bystander group, which swam with the adapted group. In both the latter groups, the time to death of the non-surviving fish was attenuated. This inter-animal communication of signals has previously been documented for animals exposed to ionizing radiation. Assays of tissues from control, challenged and 'bystander fish exposed to the pathogen showed that a signal as yet unidentified but similar to that seen in bystanders to irradiated fish was being produced. This signal caused a sharp and transient increase in intracellular calcium and a decrease in clonogenicity in a well-characterized reporter assay. PMID:25757731

  11. 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.

  12. 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...

  13. Tasers--less than lethal!

    PubMed

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-05-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself. With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  14. Tasers – Less than Lethal!

    PubMed Central

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-01-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself.With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  15. 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

  16. Effect of temperature and heating rate on apparent lethal concentrations of pyrolysis products

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Solis, A. N.; Marcussen, W. H.; Furst, A.

    1976-01-01

    The apparent lethal concentrations for 50 percent of the test animals of the pyrolysis products from twelve polymeric materials were studied as a function of temperature and heating rate. The materials were polyethylene, nylon 6, ABS, polycarbonate, polyether sulfone, polyaryl sulfone, wool fabric, aromatic polyamide fabric, polychloroprene foam, polyvinyl fluoride film, Douglas fir, and red oak. The apparent lethal concentration values of most materials vary significantly with temperature and heating rate. The apparent lethal concentration values, based on weight of sample charged, appears to effectively integrate the thermophysical, thermochemical, and physiological responses from a known quantity of material under specified imposed conditions.

  17. 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

  18. 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).

  19. 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

  20. 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

  1. 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

  2. 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…

  3. 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…

  4. Lethality of Suicide Attempt Rating Scale.

    ERIC Educational Resources Information Center

    Smith, K.; And Others

    1984-01-01

    Presents an 11-point scale for measuring the degree of lethality of suicide attempts. The scale has nine example "anchors" and uses the relative lethality of an extensive table of drugs. The scale can be used reliably by nonmedical personnel with no prior training. (Author/BL)

  5. 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

  6. 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.

  7. Lethal and sub-lethal effects of faecal deltamethrin residues on dung-feeding insects.

    PubMed

    Mann, C M; Barnes, S; Offer, B; Wall, R

    2015-06-01

    Endectocides administered to livestock to facilitate pest and parasite control may be excreted in the faeces at concentrations that are toxic to coprophagous insects, including species of ecological importance. Although much research has focused on the effects of macrocyclic lactones, relatively less attention has been given to any similar impacts of the widely used pyrethroid insecticides. Here, the effects of faecal residues of the pyrethroid deltamethrin after application to Holstein-Friesian cattle in a proprietary pour-on formulation are examined. Freshly dropped dung was collected 1, 3, 5 and 7 days after treatment and from an untreated control group. In laboratory bioasssays, female Lucilia sericata (Diptera: Calliphoridae) blow flies matured significantly smaller egg batches and had a lower percentage of eggs hatch after feeding on dung collected for up to 5 days after treatment, compared with flies feeding on dung from untreated cattle. In the field, artificial dung pats were constructed from the collected dung and left on pastureland for 7 days before being retrieved and searched for insects. Significantly more adult Diptera emerged from the faeces of untreated cattle than from the dung of treated cattle collected on days 1 and 3 after treatment. Adult Coleoptera were found in lower numbers in the dung of treated animals compared with control dung, suggesting a repellent effect. The results indicate that deltamethrin residues in cattle faeces have a range of lethal and sub-lethal effects on dung-feeding insects for up to a week after treatment, but that the precise duration and nature of toxicity varies depending on the sensitivity of the insect in question. PMID:25594879

  8. 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

  9. 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. PMID:26425902

  10. 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.

  11. Effects of some hypoxic cell radiosensitizers on the decay of potentially lethal oxygen-dependent damage in fully hydrated spores.

    PubMed Central

    Tallentire, A.; Stratford, I. J.; Maughan, R. L.; Michael, B. D.

    1978-01-01

    Using a stopped-flow mixing and pulsed irradiation apparatus, a study has been made of the decay, to a harmless form, of radiation-induced species that would otherwise be lethal to spores on contact with oxygen. Aqueous suspensions of Bacillus megaterium spores were irradiated with electrons for approximately 1 s; at various times after irradiation oxygen in solution was added. As the interval between anoxic irradiation and introduction of oxygen increased, the fraction of spores surviving increased. This change in survival reflects the decay of potentially lethal species. The presence of electron-affinic radiosensitizers during irradiation enhanced the decay rate of this damage, the greatest enhancement being seen with sensitizers of the highest electron affinity. In contrast, the nitroxyl-free radical sensitizer TAN fixed the radiation-induced damage so that no increase in survival, and hence no decay, was seen. PMID:98174

  12. 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

  13. 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

  14. Simulation and optimization of pulsed radio frequency 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

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

    2011-10-01

    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is capable of measuring dilute labile protons and microenvironmental properties. However, the CEST contrast is dependent upon experimental conditions-particularly, the radiofrequency (RF) irradiation scheme. Although continuous-wave RF irradiation has been used conventionally, the limited RF pulse duration or duty cycle of most clinical systems requires the use of pulsed RF irradiation. Here, the conventional numerical simulation is 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 or intermediate chemical exchange, simulation shows a linear regression relationship between the optimal mean RF power of pulsed-CEST MRI and continuous-wave-CEST MRI. The optimized pulsed-CEST contrast is approximately equal to that of continuous-wave-CEST MRI for exchange rates less than 50 s(-1), as confirmed experimentally using a multicompartment pH phantom. In the acute stroke animals, we showed that pulsed- and continuous-wave-amide proton CEST MRI demonstrated 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

  15. 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

  16. In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation

    SciTech Connect

    Lee, K.K.; Schraut, W.H.

    1985-04-01

    In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.

  17. Development of Synthetic Lethality Anticancer Therapeutics

    PubMed Central

    2015-01-01

    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. PMID:24893124

  18. 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)...

  19. 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

  20. Lethal Sandslides from Eolian Dunes.

    PubMed

    Loope; Mason; Dingus

    1999-11-01

    Fossil vertebrates entombed within the Upper Cretaceous Djadokhta Formation of southern Mongolia bear testimony to a heretofore unknown geologic phenomenon: mass wasting of eolian dunes during heavy rainstorms. Evaporation of shallow-penetrating rainwater led to progressive calcite accumulation in a thin layer of sand about 0.5 m below the surface of dune lee slopes. During rare heavy rainstorms, a perched water table developed at the top of calcitic zones. Positive pore water pressure led to translational slides and fast-moving sediment gravity flows that overwhelmed animals on the lee slopes of large dunes and in interdune areas. PMID:10517885

  1. 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. PMID:23802263

  2. 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.

  3. The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

    PubMed Central

    Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

    2012-01-01

    The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

  4. Radiosensitivity Parameters For Lethal Mutagenesis In Caenorhabditis Elegans

    SciTech Connect

    Cucinotta, F.A.; Wilson, J.W.; Katz, R.

    1994-01-01

    For the first time track structure theory has been applied to radiobiological effects in a living organism. Data for lethal mutagenesis in Caenorhabditis elegans, obtained after irradiation with nine different types of ions of atomic number 1-57 and gamma rays have yielded radiosensitivity parameters (E{sub 0}, sigma{sub 0}, Kappa, m = 68 Gy, 2.5 x 10(exp {minus}9) cm (exp 2), 750, 2) comparable with those found for the transformation of C3HT10 1/2 cells (180 Gy, 1.15 x 10(exp {minus}10) cm(exp 2), 750, 2) but remote from those (E{sub 0} and sigma{sub 0} = approx. 2 Gy, approx. 5 x 10(exp {minus}7) cm(exp 2)) for mammalian cell survival.

  5. 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)

  6. 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

  7. [Anthrax--continuous threat to humans and animals].

    PubMed

    Mizak, Lidia

    2004-01-01

    Gram-positive, spore-forming, aerobic bacterium Bacillus anthracis is an etiological agent of anthrax a disease very dangerous to humans and all warm-blooded animals. The spore forms are markedly resistant to unfavourable environmental extremes of heat, cold, desiccation, chemicals, irradiation etc. The vegetative forms characterised virulence factors: the antiphagocytic poly-gamma-D-polipeptide capsule and three proteins, edema factor (EF), lethal factor (LF) and protective antigen (PA). Anthrax is mainly transmitted from animals to man through food of animal origin, animal products and contamination of the environment with B. anthracis and its spores. There are three types of this disease: cutaneous, intestinal and inhalation anthrax. Research on anthrax as a biological weapon began more then 80 years ago. Depending on the target chosen and the scale of the attack the anthrax spores may by used to contaminate of foodstuffs or liquids and water. The aerosolised release of anthrax spore can cause illness with a high fatality rate. PMID:15517814

  8. 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.

  9. 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

  10. 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

  11. 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. PMID:23233475

  12. 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

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

    PubMed

    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

  14. MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the Small Animal Radiation Research Platform (SARRP).

    PubMed

    Bolcaen, Julie; Descamps, Benedicte; Deblaere, Karel; Boterberg, Tom; Hallaert, Giorgio; Van den Broecke, Caroline; Decrock, Elke; Vral, Anne; Leybaert, Luc; Vanhove, Christian; Goethals, Ingeborg

    2014-11-01

    Current glioblastoma (GB) small animal models for cranial radiation therapy (RT) use simple single beam technologies, which differ from the advanced conformal image-guided radiation techniques used in clinical practice. This technological disparity presents a major disadvantage for the development of new therapeutic approaches. Hence, we established a F98 GB rat model using magnetic resonance imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small Animal Radiation Research Platform (SARRP). Ten Fischer rats were inoculated with F98 tumor cells. When the tumor reached a volume of approximately 27 mm(3) on T2-weighted MR images, the animals were randomized into a treatment group (n = 5) receiving RT and concomitant temozolomide, and a sham group (n = 5) receiving control injections. For the treated animals, contrast-enhanced T1-weighted MR images were acquired followed by a cone-beam computed tomography (CBCT) on the SARRP system. Both scans were co-registered; MRI was used to define the target whereas CBCT was used for calculating a dose plan (20 Gy, three non-coplanar arc beams, 3 × 3 mm collimator). Tumor volumes were evaluated on follow-up contrast-enhanced T1-weighted MR images. Verification of treatment accuracy with γH2AX immunohistochemical staining was performed. Tumors in the control animals showed rapid proliferation during follow-up, encompassing almost the entire right cerebral hemisphere at day 12-15. Treated animals showed no significant tumor growth from 2 to 9 days post RT. γH2AX results confirmed the accuracy of dose delivery. This model, which is quite similar to the approach in the clinic, is valid for combined RT and chemotherapy of GB in rats. PMID:25069566

  15. 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. PMID:26097098

  16. 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

  17. 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

  18. Lethal Malaria: Marchiafava and Bignami Were Right

    PubMed Central

    White, Nicholas J.; Turner, Gareth D. H.; Day, Nicholas P. J.; Dondorp, Arjen M.

    2013-01-01

    One hundred and twenty years ago, the Italian malariologists Marchiafava and Bignami proposed that the fundamental pathological process underlying lethal falciparum malaria was microvascular obstruction. Since then, several alternative hypotheses have been proposed. These formed the basis for adjunctive interventions, which have either been ineffective or harmful. Recent evidence strongly suggests that Marchiafava and Bignami were right. PMID:23585685

  19. 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

  20. 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"…

  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. A non-lethal technique for detecting the chytrid fungus Batrachochytrium dendrobatidis on tadpoles.

    PubMed

    Retallick, Richard W R; Miera, Verma; Richards, Kathryn L; Field, Kimberleigh J; Collins, James P

    2006-09-14

    Batrachochytrium dendrobatidis (Bd) infection on post-metamorphic frogs and salamanders is commonly diagnosed using polymerase chain reaction (PCR) of skin scrapings taken with mildly abrasive swabs. The technique is sensitive, non-lethal, and repeatable for live animals. Tadpoles are generally not sampled by swabbing but are usually killed and their mouthparts excised to test for the pathogen. We evaluated a technique for non-lethal Bd diagnosis using quantitative PCR (qPCR) on swabs scraped over the mouthparts of live tadpoles. The sensitivity of non-lethal (swabbing) and lethal (removal of mouthparts) sampling was assessed using 150 Bd-infected Rana subaquavocalis tadpoles. Swabbing was consistently less sensitive than lethal sampling, but still detected Bd. Experimental Bd prevalence was 41.1% when estimated by destructively sampling mouthparts and 4.7 to 36.6% (mean = 21.4%) when estimated with swabs. Detection rates from swabbing varied with investigator and time since infection. The likelihood of detecting Bd-infected tadpoles was similar regardless of size and developmental stage. Swabbing mouthparts of live tadpoles is a feasible and effective survey technique for Bd, but, because it is less sensitive, more tadpoles must be sampled to estimate prevalence at a confidence level comparable to destructive sampling. PMID:17067076

  3. 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. PMID:27325648

  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. [Variability of the dose effect in the radio-biologic experimentation on animals. Third communication: Influence of breed, sex, age as well as radiation dose on body weight and survival time in days after whole-body irradiation of Wistar and Siv-50 rats (author's transl)].

    PubMed

    Peters, R; Sailer, U; Peters, K

    1981-02-01

    After a whole-body irradiation of Wistar and Siv-50 rat males and females with 600 to 900 R, the survival times and the development of weight of the irradiated animals were determined and compared. The development of body weight was influenced by the dose administered as well as by age, sex and breed of the animals. Furthermore, the weight curves showed also characteristic analogies. During a period of 30 days after the irradiation, there are generally two phases with a considerable weight loss which are both accompanied by a reduced absorption of drinking-water and the appearance of a gastrointestinal and hemopoietic irradiation damage as well as the resulting activity increase of the pituitary gland and the cortex of the suprarenal gland. The weight recovery occurring after sublethal radiation doses is also influenced by the administered dose and the age of the animals. The dropping weight curves of dying animals are equally dependent on the administered dose. With regard to the survival time in days in dependence upon the administered dose and the age of the animals, the authors proved that the survival time of the finally dying animals becomes longer as their radioresistance increases. During the last phase of the 30 days' experimentation, females show a markedly increased death rate whereas males seem to have continually better survival chances when they are still alive at the last phase. PMID:7222132

  6. 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.

  7. Tumour necrosis factor alpha antibody protects against lethal meningococcaemia.

    PubMed

    Nassif, X; Mathison, J C; Wolfson, E; Koziol, J A; Ulevitch, R J; So, M

    1992-03-01

    Tumour necrosis factor alpha (TNF-alpha) has been shown to be the principal mediator of Gram-negative bacterial endotoxin-induced shock. Nevertheless, evidence suggests that TNF-alpha plays a beneficial role in controlling bacterial infections when multiplication of the microorganism is required to kill the host. Using an infant rat model of Neisseria meningitidis infection, we found that blood TNF-alpha concentration reaches a peak three hours after intraperitoneal injection of 3 x 10(6) bacteria. Thereafter, the level of TNF-alpha decreased and was undetectable six to eight hours after infection. A correlation was observed between the magnitude of initial TNF-alpha response and a fatal outcome. Pretreatment of the animals with polyclonal anti-TNF antiserum significantly reduced mortality relative to animals pretreated with control serum. However, pretreatment of animals with anti-TNF antibody did not alter the bacterial invasion of the cerebrospinal fluid. Injection of heat-killed bacteria did not cause death and induced lower TNF-alpha levels than the same number of live bacteria. This excludes the possibility that the role of TNF-alpha is to mediate a shock induced by the endotoxin component of the bacterial inoculum. These results indicate that TNF-alpha has a deleterious effect in this model of bacteraemia. Identification of the critical factors that determine the action of TNF-alpha during lethal bacteraemia will lead to a better understanding of these diseases and the development of appropriate therapeutic intervention. PMID:1552859

  8. Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia.

    PubMed

    Kim, Dong Won; Lee, Jae-Chul; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Seo, Jeong Yeol; Cho, Jun Hwi; Kang, Il Jun; Hong, Seongkweon; Kim, Young-Myeong; Won, Moo-Ho; Kim, In Hye

    2015-09-01

    Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia could reduce neuronal damage/death following a subsequent lethal transient cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2 and tumor necrosis factor (TNF)-α as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between animals with lethal ischemia and ones with IPC followed by lethal ischemia. In the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however, IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions of all cytokines were significantly decreased in the SP after lethal ischemia and hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4 and IL-13) in the stratum pyramidale of the CA1 region following no lethal ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC were continuously maintained is the SP of the CA1 region after lethal ischemia. However, pro-inflammatory cytokines (IL-2 and TNF-α) in the SP of the CA1 region were similar those in the sham-operated animals with IPC, and the IL-4 and IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion, this study shows that anti-inflammatory cytokines significantly increased and longer maintained by IPC and this might be closely associated with neuroprotection after lethal transient cerebral ischemia. PMID:26290267

  9. [The role of different species of hunt game animals in formation of irradiation dose of population in territories polluted by 137Cs].

    PubMed

    Pel'gunov, A N; Pel'gunova, L A

    2009-01-01

    This article includes the data on 137Cs accumulation in different species of game animals studied in two regions of Bryansk area. Based on Hunting Commission data on numbers of bagging by hunters in these regions, a count of total hunting production polluted with 137Cs was obtained. It was shown that wild ungulates are the main dose-forming factor in risk group. A calculation of volume of 137Cs transferred from forest biocenosi into towns and villages of the regions in question was also performed. PMID:19507694

  10. 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

  11. 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

  12. Henipaviruses-unanswered questions of lethal zoonoses.

    PubMed

    Field, Hume; Kung, Nina

    2011-12-01

    The highly lethal Hendra and Nipah viruses have been described for little more than a decade, yet within that time have been aetiologically associated with major livestock and human health impacts, albeit on a limited scale. Do these emerging pathogens pose a broader threat, or are they inconsequential 'viral chatter'. Given their lethality, and the evident multi-generational human-to-human transmission associated with Nipah virus in Bangladesh, it seems prudent to apply the precautionary principle. While much is known of their clinical, pathogenic and epidemiologic features in livestock species and humans, a number of fundamental questions regarding the relationship between the viruses, their natural fruit-bat host and the environment remain unanswered. In this paper, we pose and probe these questions in context, and offer perspectives based primarily on our experience with Hendra virus in Australia, augmented with Nipah virus parallels. PMID:22440924

  13. Synthetic lethal approaches to breast cancer therapy.

    PubMed

    Rehman, Farah L; Lord, Christopher J; Ashworth, Alan

    2010-12-01

    The promise of personalized therapy for breast cancer is that therapeutic efficacy will be increased while toxic effects are reduced to a minimum. To achieve this goal, there is now an emphasis on the design of therapies that are based not only on the clinical manifestations of the disease, but also on the underlying molecular and cellular biology of cancer. However, identifying targets for personalized therapies in breast cancer is challenging. Here, we describe how biological concepts such as synthetic lethality and oncogene addiction can be used to identify new therapeutic targets and approaches. We discuss the current clinical developments in implementing synthetic lethality therapies, and highlight new ways in which this approach could be used to target specific subsets of breast cancer. PMID:20956981

  14. 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

  15. 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

  16. The population genetics of synthetic lethals.

    PubMed

    Phillips, P C; Johnson, N A

    1998-09-01

    Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial. Here, we derive the expected frequencies for SDL under a mutation-selection balance for the complete haploid model and selected cases of the diploid model. We have also obtained simple approximations that demonstrate good fit to exact solutions based on numerical iterations. In the haploid case, equilibrium frequencies of carrier haplotypes (individuals with only a single mutation) are comparable to analogous single-locus results, after allowing for the effects of linkage. Frequencies in the diploid case, however, are much higher and more comparable to the square root of the single-locus results. In particular, when selection operates only on the double-mutant homozygote and linkage is not too tight, the expected frequency of the carriers is approximately the quartic root of the ratio between the mutation rate and the selection coefficient of the synthetics. For a reasonably wide set of models, the frequencies of carriers can be on the order of a few percent. The equilibrium frequencies of these deleterious alleles can be relatively high because, with SDL, both dominance and epistasis act to shield carriers from exposure to selection. We also discuss the possible role of SDL in maintaining genetic variation and in hybrid breakdown. PMID:9725860

  17. 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

  18. 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

  19. Engineered Repressible Lethality for Controlling the Pink Bollworm, a Lepidopteran Pest of Cotton

    PubMed Central

    Morrison, Neil I.; Simmons, Gregory S.; Fu, Guoliang; O’Connell, Sinead; Walker, Adam S.; Dafa’alla, Tarig; Walters, Michelle; Claus, John; Tang, Guolei; Jin, Li; Marubbi, Thea; Epton, Matthew J.; Harris, Claire L.; Staten, Robert T.; Miller, Ernest; Miller, Thomas A.; Alphey, Luke

    2012-01-01

    The sterile insect technique (SIT) is an environmentally friendly method of pest control in which insects are mass-produced, irradiated and released to mate with wild counterparts. SIT has been used to control major pest insects including the pink bollworm (Pectinophora gossypiella Saunders), a global pest of cotton. Transgenic technology has the potential to overcome disadvantages associated with the SIT, such as the damaging effects of radiation on released insects. A method called RIDL (Release of Insects carrying a Dominant Lethal) is designed to circumvent the need to irradiate insects before release. Premature death of insects’ progeny can be engineered to provide an equivalent to sterilisation. Moreover, this trait can be suppressed by the provision of a dietary antidote. In the pink bollworm, we generated transformed strains using different DNA constructs, which showed moderate-to-100% engineered mortality. In permissive conditions, this effect was largely suppressed. Survival data on cotton in field cages indicated that field conditions increase the lethal effect. One strain, called OX3402C, showed highly penetrant and highly repressible lethality, and was tested on host plants where its larvae caused minimal damage before death. These results highlight a potentially valuable insecticide-free tool against pink bollworm, and indicate its potential for development in other lepidopteran pests. PMID:23226548

  20. Engineered repressible lethality for controlling the pink bollworm, a lepidopteran pest of cotton.

    PubMed

    Morrison, Neil I; Simmons, Gregory S; Fu, Guoliang; O'Connell, Sinead; Walker, Adam S; Dafa'alla, Tarig; Walters, Michelle; Claus, John; Tang, Guolei; Jin, Li; Marubbi, Thea; Epton, Matthew J; Harris, Claire L; Staten, Robert T; Miller, Ernest; Miller, Thomas A; Alphey, Luke

    2012-01-01

    The sterile insect technique (SIT) is an environmentally friendly method of pest control in which insects are mass-produced, irradiated and released to mate with wild counterparts. SIT has been used to control major pest insects including the pink bollworm (Pectinophora gossypiella Saunders), a global pest of cotton. Transgenic technology has the potential to overcome disadvantages associated with the SIT, such as the damaging effects of radiation on released insects. A method called RIDL (Release of Insects carrying a Dominant Lethal) is designed to circumvent the need to irradiate insects before release. Premature death of insects' progeny can be engineered to provide an equivalent to sterilisation. Moreover, this trait can be suppressed by the provision of a dietary antidote. In the pink bollworm, we generated transformed strains using different DNA constructs, which showed moderate-to-100% engineered mortality. In permissive conditions, this effect was largely suppressed. Survival data on cotton in field cages indicated that field conditions increase the lethal effect. One strain, called OX3402C, showed highly penetrant and highly repressible lethality, and was tested on host plants where its larvae caused minimal damage before death. These results highlight a potentially valuable insecticide-free tool against pink bollworm, and indicate its potential for development in other lepidopteran pests. PMID:23226548

  1. Influence of nuclear structure on the formation of radiation-induced lethal lesions.

    PubMed

    Friedman, Daniel A; Tait, Lauren; Vaughan, Andrew T M

    2016-05-01

    Purpose The rejoining of fragmented nuclear DNA caused by ionizing radiation may lead to lethal chromosome rearrangements, such as rings or dicentrics. The clinically useful linear quadratic relationship between dose and cell survival has been interpreted as the generation of lethal lesions secondary to damage occurring in two separate chromosomes simultaneously (α component), or as potentially repairable separate events (β component). Here, the generation of such lesions is discussed, synthesizing existing knowledge with new insights gleaned from spatial proximity data made possible by high-throughput sequencing of chromosome conformation capture experiments. Over a range of several Mbp, the linear DNA strand is organized as a fractal globule generating multiple sites of contact that may facilitate deletions or inversions if the points of contact are damaged. On a larger scale, transcriptionally active euchromatin occupies a physically identifiable space separate from inactive areas and is preferentially susceptible to free radical attack after irradiation. Specific transcriptional programs link genomic locations within that space, potentially enhancing their interaction if subject to simultaneous fragmentation by a single radiation event. Conclusions High throughput spatial analysis of the factors that control chromosome proximity has the potential to better describe the formation of the lethal chromosome aberrations that kill irradiated cells. PMID:26917327

  2. 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…

  3. 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

  4. Lethal and non-lethal violence against women in Australia: measurement challenges, conceptual frameworks, and limitations in knowledge.

    PubMed

    McPhedran, Samara; Baker, Jeanine

    2012-08-01

    Understanding pathways from non-lethal violence to lethal violence between intimate partners is a notable challenge for both policy and practice in partner violence prevention. Of particular interest is whether lethal violence represents an "escalation" of violence from "low" to "high" risk over time, or is best predicted by specific behavioral "typologies" of perpetrators. Testing the "escalation" and "typology" theories is hampered in Australia by limitations in knowledge about non-lethal and lethal violence against women. This article discusses data limitations, measurement problems, and conceptual shortcomings, and suggests approaches to improving evidence quality in the field of violence prevention and risk assessment. PMID:23008430

  5. Mutation induced extinction in finite populations: lethal mutagenesis and lethal isolation.

    PubMed

    Wylie, C Scott; Shakhnovich, Eugene I

    2012-01-01

    Reproduction is inherently risky, in part because genomic replication can introduce new mutations that are usually deleterious toward fitness. This risk is especially severe for organisms whose genomes replicate "semi-conservatively," e.g. viruses and bacteria, where no master copy of the genome is preserved. Lethal mutagenesis refers to extinction of populations due to an unbearably high mutation rate (U), and is important both theoretically and clinically, where drugs can extinguish pathogens by increasing their mutation rate. Previous theoretical models of lethal mutagenesis assume infinite population size (N). However, in addition to high U, small N can accelerate extinction by strengthening genetic drift and relaxing selection. Here, we examine how the time until extinction depends jointly on N and U. We first analytically compute the mean time until extinction (τ) in a simplistic model where all mutations are either lethal or neutral. The solution motivates the definition of two distinct regimes: a survival phase and an extinction phase, which differ dramatically in both how τ scales with N and in the coefficient of variation in time until extinction. Next, we perform stochastic population-genetics simulations on a realistic fitness landscape that both (i) features an epistatic distribution of fitness effects that agrees with experimental data on viruses and (ii) is based on the biophysics of protein folding. More specifically, we assume that mutations inflict fitness penalties proportional to the extent that they unfold proteins. We find that decreasing N can cause phase transition-like behavior from survival to extinction, which motivates the concept of "lethal isolation." Furthermore, we find that lethal mutagenesis and lethal isolation interact synergistically, which may have clinical implications for treating infections. Broadly, we conclude that stably folded proteins are only possible in ecological settings that support sufficiently large populations

  6. 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

  7. 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. PMID:14608825

  8. 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

  9. A Toxin-Antitoxin Module in Bacillus subtilis Can Both Mitigate and Amplify Effects of Lethal Stress

    PubMed Central

    Wu, Xiangli; Wang, Xiuhong; Drlica, Karl; Zhao, Xilin

    2011-01-01

    Background Bacterial type-2 (protein-protein) toxin-antitoxin (TA) modules are two-gene operons that are thought to participate in the response to stress. Previous work with Escherichia coli has led to a debate in which some investigators conclude that the modules protect from stress, while others argue that they amplify lethal stress and lead to programmed cell death. To avoid ambiguity arising from the presence of multiple TA modules in E. coli, the effect of the sole type-2 toxin-antitoxin module of Bacillus subtilis was examined for several types of lethal stress. Methodology/Principal Findings Genetic knockout of the toxin gene, ndoA (ydcE), conferred protection to lethal stressors that included kanamycin, moxifloxacin, hydrogen peroxide, and UV irradiation. However, at low doses of UV irradiation the ndoA deficiency increased lethality. Indeed, gradually increasing UV dose with the ndoA mutant revealed a crossover response – from the mutant being more sensitive than wild-type cells to being less sensitive. For high temperature and nutrient starvation, the toxin deficiency rendered cells hypersensitive. The ndoA deficiency also reduced sporulation frequency, indicating a role for toxin-antitoxin modules in this developmental process. In the case of lethal antimicrobial treatment, deletion of the toxin eliminated a surge in hydrogen peroxide accumulation observed in wild-type cells. Conclusions A single toxin-antitoxin module can mediate two opposing effects of stress, one that lowers lethality and another that raises it. Protective effects are thought to arise from toxin-mediated inhibition of translation based on published work. The enhanced, stress-mediated killing probably involves toxin-dependent accumulation of reactive oxygen species, since a deficiency in the NdoA toxin suppressed peroxide accumulation following antimicrobial treatment. The type and perhaps the level of stress appear to be important for determining whether this toxin will have a

  10. 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

  11. 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

  12. 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.

  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. PMID:24867061

  14. 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.

  15. [Acute lethal alcohol intoxication (author's transl)].

    PubMed

    Kringsholm, B

    1976-01-01

    In 14,744 autopsy cases from an 18-year period 92 cases (of which 7 were ruled out because of decomposition were observed in which death was supposed to be due to direct acute alcoholic intoxication. In the police reports 81 persons were designated as chronic alcoholics or abusers of spirits. The blood alcohol level ranged between 2.04 and 4.92 o/oo. The cases studied were divided into two groups, one with low and the other with high lethal alcohol level. Fatty liver and cirrhosis were found with identical frequency in the two groups, whereas cardiac hypertrophy of obscure origin occurred markedly more often in the group with low lethal blood alcohol level. On the basis the possible mechanism of death in the cases with cardiac hypertrophy is discussed. Finally, the relation between the blood and urine alcohol concentrations observed in 72 cases is discussed. On the assumption that the water phase of the blood was 75 per cent of the total blood, death occurred in the persons without cardiac hypertrophy with fairly identical frequency either in the phase of absorption or the phase of elimination, whereas in the persons with cardiac hypertrophy death most often occurred in the phase of absorption. These statements should, however, be taken with some reservation, partly because the water phase of the blood may vary considerably post mortem (60-90 per cent) and partly because the urine alcohol concentration depends on serval variable factors. PMID:137612

  16. 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

  17. Lethal outcomes in Klippel-Trenaunay syndrome.

    PubMed

    Karunamurthy, Arivarasan; Pantanowitz, Liron; Lepe, Jorge Guzman; Reyes-Múgica, Miguel

    2013-01-01

    Klippel-Trenaunay syndrome (KTS) is an uncommon congenital angiodysplasia that manifests in infancy and is characterized by venous and lymphatic malformations of the skin, soft tissue, and bone causing limb hypertrophy. We report 2 patients with long-term KTS who developed lethal complications from uncommon and unusual manifestations. The 1st patient was a female with KTS who at 2 years of age underwent a below-the-knee amputation for a massively hypertrophied and malformed left foot. Two years later she required additional surgical removal of vascular malformations involving her left calf with extension to the groin, pubis, and ipsilateral abdomen. Fifteen years later she underwent splenectomy (400 g) revealing multifocal, cystically dilated vascular channels distorting the splenic architecture and died suddenly of massive intra-abdominal hemorrhage on the 2nd postoperative day. The 2nd patient was a 72-year-old male with long-standing KTS who presented with debilitating chronic penile and scrotal edema. Surgical excision of his lymphedematous scrotal and penile skin revealed a low-grade angiosarcoma arising in the setting of chronic lymphedema. The patient died shortly after surgery from massive hemorrhage due to traumatic rupture of malformed leg vessels. KTS may lead to significant morbidity and mortality, and pathologic consequences from long-term KTS have been rarely reported. These cases illustrate the risk of lethal hemorrhage, organomegaly from protracted vascular malformation, and development of vascular neoplasia associated with chronic lymphedema in KTS. PMID:23915076

  18. Enhancing CHK1 inhibitor lethality in glioblastoma.

    PubMed

    Tang, Yong; Dai, Yun; Grant, Steven; Dent, Paul

    2012-04-01

    The present studies were initiated to determine whether inhibitors of MEK1/2 or SRC signaling, respectively, enhance CHK1 inhibitor lethality in primary human glioblastoma cells. Multiple MEK1/2 inhibitors (CI-1040 (PD184352); AZD6244 (ARRY-142886)) interacted with multiple CHK1 inhibitors (UCN-01, AZD7762) to kill multiple primary human glioma cell isolates that have a diverse set of genetic alterations typically found in the disease. Inhibition of SRC family proteins also enhanced CHK1 inhibitor lethality. Combined treatment of glioma cells with (MEK1/2 + CHK1) inhibitors enhanced radiosensitivity. Combined (MEK1/2 + CHK1) inhibitor treatment led to dephosphorylation of ERK1/2 and S6 ribosomal protein, whereas the phosphorylation of JNK and p38 was increased. MEK1/2 + CHK1 inhibitor-stimulated cell death was associated with the cleavage of pro-caspases 3 and 7 as well as the caspase substrate (PARP). We also observed activation of pro-apoptotic BCL-2 effector proteins BAK and BAX and reduced levels of pro-survival BCL-2 family protein BCL-XL. Overexpression of BCL-XL alleviated but did not completely abolish MEK1/2 + CHK1 inhibitor cytotoxicity in GBM cells. These findings argue that multiple inhibitors of the SRC-MEK pathway have the potential to interact with multiple CHK1 inhibitors to kill glioma cells. PMID:22313687

  19. Lethal domestic violence in eastern North Carolina.

    PubMed

    Gilliland, M G; Spence, P R; Spence, R L

    2000-01-01

    Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

  20. 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.

  1. 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.

  2. 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

  3. 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

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

    PubMed Central

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

    2013-01-01

    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

  5. 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 ...

  6. Animal Bites

    MedlinePlus

    ... and complications from bites Never pet, handle, or feed unknown animals Leave snakes alone Watch your children closely around animals Vaccinate your cats, ferrets, and dogs against rabies Spay or neuter ...

  7. 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.

  8. 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. PMID:19923138

  9. 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. PMID:14687768

  10. Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli.

    PubMed

    Hinshaw, L B; Beller, B K; Chang, A C; Murray, C K; Flournoy, D J; Passey, R B; Archer, L T

    1985-01-01

    Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses. A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E. coli. The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E. coli. Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E. coli administration and with GS after administration of all E. coli. Animals given only E. coli died in 2.6 (+/- 0.3) hours, while those given no E. coli, or E. coli plus steroid/antibiotic, survived longer than 100 hours. Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions. Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E. coli infusion. Findings indicate that animals treated with MPSS/GS after E. coli ultimately succumbed to adrenal insufficiency rather than from the E. coli insult and thus recovery from shock itself was complete. PMID:3902272

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

    PubMed Central

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

    2009-01-01

    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 LD50 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. PMID:19335549

  12. 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

  13. 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.

  14. Variation Between Strains of Hamsters in the Lethality of Pichinde Virus Infections

    PubMed Central

    Buchmeier, Michael J.; Rawls, William E.

    1977-01-01

    Infection by Pichinde virus, a member of the arenavirus group, was studied in Golden Syrian hamsters (Mesocricetus auratus) with regard to possible mechanisms of resistance to virus infection in adult hamsters. Two hamster strains were found to differ in their susceptibility to lethal Pichinde virus infection. LVG/Lak randomly bred hamsters were found to be 100% susceptible to low doses of Pichinde virus during the first 6 days of life, but after 8 days of life, mortality was uncommon. Peak virus titers in the serum of animals infected at 3 days of life were 4 logs greater than in animals infected at 12 days. MHA/Lak inbred hamsters, in contrast, were found to be susceptible to lethal virus infection both as newborns and as adults. Peak virus titers of greater than 108 plaque-forming units/ml were observed in serum 8 days after infection of adult MHA hamsters as compared with less than 103 plaque-forming units/ml in the serum of adult LVG hamsters. Cultured primary kidney cells and peritoneal macrophages from either hamster strain supported Pichinde virus replication equally well in vitro. Antibodies to the complement-fixing antigens and to antigens at the surface of virus-infected cells were produced by both strains of hamsters. Cyclophosphamide immunosuppression rendered adult LVG animals susceptible to lethal infections, and virus grew to high titers in the treated animals. These findings suggest that immunological factors that appear early in life in LVG hamsters and are deficient in MHA hamsters limit Pichinde virus infection. Unlike previously reported arenavirus diseases, the observations suggest that death is produced by a direct viral effect and not through immunopathological mechanisms. PMID:193786

  15. 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

  16. 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

  17. 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

  18. Lethal and sub-lethal effects of spinosad on bumble bees (Bombus impatiens Cresson).

    PubMed

    Morandin, Lora A; Winston, Mark L; Franklin, Michelle T; Abbott, Virginia A

    2005-07-01

    Recent developments of new families of pesticides and growing awareness of the importance of wild pollinators for crop pollination have stimulated interest in potential effects of novel pesticides on wild bees. Yet pesticide toxicity studies on wild bees remain rare, and few studies have included long-term monitoring of bumble bee colonies or testing of foraging ability after pesticide exposure. Larval bees feeding on exogenous pollen and exposed to pesticides during development may result in lethal or sub-lethal effects during the adult stage. We tested the effects of a naturally derived biopesticide, spinosad, on bumble bee (Bombus impatiens Cresson) colony health, including adult mortality, brood development, weights of emerging bees and foraging efficiency of adults that underwent larval development during exposure to spinosad. We monitored colonies from an early stage, over a 10-week period, and fed spinosad to colonies in pollen at four levels: control, 0.2, 0.8 and 8.0 mg kg(-1), during weeks 2 through 5 of the experiment. At concentrations that bees would likely encounter in pollen in the wild (0.2-0.8 mg kg(-1)) we detected minimal negative effects to bumble bee colonies. Brood and adult mortality was high at 8.0 mg kg(-1) spinosad, about twice the level that bees would be exposed to in a 'worst case' field scenario, resulting in colony death two to four weeks after initial pesticide exposure. At more realistic concentrations there were potentially important sub-lethal effects. Adult worker bees exposed to spinosad during larval development at 0.8 mg kg(-1) were slower foragers on artificial complex flower arrays than bees from low or no spinosad treated colonies. Inclusion of similar sub-lethal assays to detect effects of pesticides on pollinators would aid in development of environmentally responsible pest management strategies. PMID:15880684

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. [Transgenic animals and animal welfare

    PubMed

    Reinhardt, Christoph

    1998-01-01

    Under the pressure of a public vote in Switzerland (7 June 1998) on an initiative to ban the production, use and patenting of transgenic animals, their value for biomedical research and development is intensely debated. In addition, the Swiss legislation has adopted (1992) a constitutional obligation to "take into account the dignity of creatures". The term "dignity of creatures", however, can be interpreted in anthropocentric or biocentric ways. The government has now formulated the legal implications of this term for transgenic animals and plants in various laws including the animal and environmental protection laws. This paper gives arguments for a fair evaluation of trangenic animals from an animal welfare point of view where not only the costs of animal suffering must be considered but also the probability of potential benefit for man. A self-confident research community should allow such an evaluation procedure even in view of an outcome which could ban many uses of transgenic animals PMID:11208266

  6. 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...

  7. 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

  8. Early lethality of shRNA-transgenic pigs due to saturation of microRNA pathways* #

    PubMed Central

    Dai, Zhen; Wu, Rong; Zhao, Yi-cheng; Wang, Kan-kan; Huang, Yong-ye; Yang, Xin; Xie, Zi-cong; Tu, Chang-chun; Ouyang, Hong-sheng; Wang, Tie-dong; Pang, Da-xin

    2014-01-01

    RNA interference (RNAi) is considered as a potential modality for clinical treatment and anti-virus animal breeding. Here, we investigate the feasibility of inhibiting classical swine fever virus (CSFV) replication by short hairpin RNA (shRNA) in vitro and in vivo. We generate four different shRNA-positive clonal cells and two types of shRNA-transgenic pigs. CSFV could be effectively inhibited in shRNA-positive clonal cells and tail tip fibroblasts of shRNA-transgenic pigs. Unexpectedly, an early lethality due to shRNA is observed in these shRNA-transgenic pigs. With further research on shRNA-positive clonal cells and transgenic pigs, we report a great induction of interferon (IFN)-responsive genes in shRNA-positive clonal cells, altered levels of endogenous microRNAs (miRNA), and their processing enzymes in shRNA-positive cells. What is more, abnormal expressions of miRNAs and their processing enzymes are also observed in the livers of shRNA-transgenic pigs, indicating saturation of miRNA/shRNA pathways induced by shRNA. In addition, we investigate the effects of shRNAs on the development of somatic cell nuclear transfer (SCNT) embryos. These results show that shRNA causes adverse effects in vitro and in vivo and shRNA-induced disruption of the endogenous miRNA pathway may lead to the early lethality of shRNA-transgenic pigs. We firstly report abnormalities of the miRNA pathway in shRNA-transgenic animals, which may explain the early lethality of shRNA-transgenic pigs and has important implications for shRNA-transgenic animal preparation. PMID:24793764

  9. Tumor clone dynamics in lethal prostate cancer

    PubMed Central

    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; de Bono, Johann S.; Demichelis, Francesca; Attard, Gerhardt

    2015-01-01

    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. PMID:25232177

  10. 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.

  11. Lethal methemoglobinemia and automobile exhaust inhalation.

    PubMed

    Vevelstad, Merete; Morild, Inge

    2009-05-30

    Inhalation of automobile exhaust gas often leads to death by CO intoxication. In some cases the measured carbon monoxide hemoglobin saturation level (COHb) is considerably below what is considered to be lethal. The death in such cases has been attributed to a combination of a high CO2 and a low O2 tension. In a recent case the deceased was found dead in a car equipped with a catalytic converter, with a hose leading exhaust from the engine to the interior of the car. Analysis revealed a moderately elevated COHb and a high methemoglobin saturation level (MetHb) in peripheral blood. No ethanol, narcotics or drugs were detected. Reports mentioning MetHb or methemoglobinemia in post-mortem cases are surprisingly scarce, and very few have related exhaust gas deaths to methemoglobinemia. High-degree methemoglobinemia causes serious tissue hypoxia leading to unconsciousness, arrhythmia and death. The existing literature in this field and the knowledge that exhaust fumes contain nitrogen oxide gases (NOx) that by inhalation and absorption can result in severe methemoglobinemia, led us to postulate that this death could possibly be attributed to a combination of methemoglobinemia and a moderately high COHb concentration. PMID:19261402

  12. Pharmacological antagonism of lethal effects induced by O-isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate.

    PubMed

    Chang, F C T; Hoffman, B E; DeBus, S

    2002-08-01

    O-Isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate (VR) is a structural isomer of a more widely known chemical warfare agent O-ethyl S-[2(diisopropylamino)ethyl]methylphosphonothioate (VX). VR has the potential of being used as military threat/sabotage/terrorist agent. The development of a sound medical countermeasure will undoubtedly enhance not only our medical readiness and ability in VR casualty management, but also our defense posture against the deployment of VR in both combat and politically volatile environments. Acute exposure to a lethal dose of VR has been shown to cause cholinergic hyperfunction, incapacitation, seizures, convulsions, cardiorespiratory depression and death. In this study, pharmacological antagonism of VR-induced cardiorespiratory failure and lethality was investigated in guinea pigs chronically instrumented for concurrent recordings of electrocorticogram, diaphragmatic EMG, Lead II ECG, heart rate and neck skeletal muscle EMG. Thirty (30) min prior to intoxication with a 2 x LD50 dose of VR (22.6 micrograms/kg, s.c.), animals were pretreated with pyridostigmine (0.026 mg/kg, i.m.). Immediately after VR intoxication, animals were given pralidoxime chloride (2-PAM; 25 mg/kg, i.m.) and atropine sulfate (2, 8 or 16 mg/kg, i.m.). In animals that displayed seizures and convulsions, diazepam (5 mg/kg, i.m.) was administered 10 min following the onset of epileptiform activities. Responses to pretreatment/therapy modality were evaluated at 24 h post-VR. All animals survived the 2 x LD50 VR challenge. With the exception of an increased heart rate in response to atropine, the myocardial and diaphragmatic (respiratory) activity profiles appeared normal throughout the course of intoxication and recovery. Animals receiving 2 mg/kg atropine all developed fasciculations, seizures, signs of excessive mucoid/salivary secretion, and needed diazepam adjunct therapy. One-half (50%) of the animals receiving 8 mg/kg atropine developed seizure

  13. 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

  14. 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

  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. 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.

  17. 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.

  18. Small animal radiotherapy research platforms

    NASA Astrophysics Data System (ADS)

    Verhaegen, Frank; Granton, Patrick; Tryggestad, Erik

    2011-06-01

    Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research.

  19. Lethal and Amanitin-Resistance Mutations in the Caenorhabditis Elegans Ama-1 and Ama-2 Genes

    PubMed Central

    Rogalski, T. M.; Bullerjahn, AME.; Riddle, D. L.

    1988-01-01

    Mutants of Caenorhabditis elegans resistant to α-amanitin have been isolated at a frequency of about 1.6 X 10(-6) after EMS mutagenesis of the wild-type strain, N2. Four new dominant resistance mutations have been studied genetically. Three are alleles of a previously identified gene, ama-1 IV, encoding the largest subunit of RNA polymerase II. The fourth mutation defines a new gene, ama-2 V. Unlike the ama-1 alleles, the ama-2 mutation exhibits a recessive-lethal phenotype. Growth and reproduction of N2 was inhibited at a concentration of 10 μg/ml amanitin, whereas ama-2/+ animals were inhibited at 100 μg/ml, and 800 μg/ml was required to inhibit growth of ama-1/+ larvae. We have also determined that two reference strains used for genetic mapping, dpy-11(e224)V and sma-1(e30)V, are at least four-fold more sensitive to amanitin that the wild-type strain. Using an amanitin-resistant ama-1(m118) or ama-1(m322) strain as a parent, we have isolated amanitin-sensitive mutants that carry recessive-lethal ama-1 alleles. The frequency of EMS-induced lethal ama-1 mutations is approximately 1.7 X 10(-3), 1000-fold higher than the frequency of amanitin-resistance alleles. Nine of the lethal alleles are apparent null mutations, and they exhibit L1-lethal phenotypes at both 20° and 25°. Six alleles result in partial loss of RNA polymerase II function as determined by their sterile phenotypes at 20°. All but one of these latter mutations exhibit a more severe phenotype at 25°C. We have also selected seven EMS-induced revertants of three different ama-1 lethals. These revertants restore dominant resistance to amanitin. The selection for revertants also produced eight new dominant amanitin resistance alleles on the balancer chromosome, nT1. PMID:3197954

  20. 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…

  1. Factors Affecting Lethal Isotherms During Cryoablation Procedures

    PubMed Central

    Rau, Andrew C.; Siskey, Ryan; Ochoa, Jorge A.; Good, Tracy

    2016-01-01

    Background: Creating appropriately-sized, lethal isotherms during cryoablation of renal tumors is critical in order to achieve sufficiently-sized zones of cell death. To ensure adequate cell death in target treatment locations, surgeons must carefully select the type, size, location, and number of probes to be used, as well as various probe operating parameters. Objective: The current study investigates the effects of probe type, operating pressure, and clinical method on the resulting sizes of isotherms in an in vitro gelatin model. Method: Using a total of four cryoprobes from two manufacturers, freeze procedures were conducted in gelatin in order to compare resulting sizes of constant temperature zones (isotherms). The effects of certain procedural parameters which are clinically adjustable were studied. Results: Test results show that the sizes of 0 °C,-20 °C and -40 °C isotherms created by similarly-sized probes from two different manufacturers were significantly different for nearly all comparisons made, and that size differences resulting from changing the operating pressure were not as prevalent. Furthermore, isotherm sizes created using a multiple freeze procedure (a ten minute freeze, followed by a five minute passive thaw, followed by another ten minute freeze) did not result in statistically-significant differences when compared to those created using a single freeze procedure in all cases. Conclusion: These results indicate that selection of the probe manufacturer and probe size may be more important for dictating the size of kill zones during cryoablation than procedural adjustments to operating pressures or freeze times.

  2. 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.

  3. 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

  4. 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. PMID:16501652

  5. Lethal phenotype in conditional late-onset arginase 1 deficiency in the mouse

    PubMed Central

    Kasten, Jennifer; Hu, Chuhong; Bhargava, Ragini; Park, Hana; Tai, Denise; Byrne, James A.; Marescau, Bart; De Deyn, Peter P.; Schlichting, Lisa; Grody, Wayne W.; Cederbaum, Stephen D.; Lipshutz, Gerald S.

    2013-01-01

    Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia, which lead to neurological impairment with spasticity, loss of ambulation, seizures, and severe mental and growth retardation; uncommonly, patients suffer early death from this disorder. In a murine targeted knockout model, onset of the phenotypic abnormality is heralded by weight loss at around day 15, and death occurs typically by postnatal day 17 with hyperargininemia and markedly elevated ammonia. This discrepancy between the more attenuated juvenile-onset human disease and the lethal neonatal murine model has remained suboptimal for studying and developing therapy for the more common presentation of argianse deficiency. These investigations aimed to address this issue by creating an adult conditional knockout mouse to determine whether later onset of arginase deficiency also resulted in lethality. Animal survival and ammonia levels, body weight, circulating amino acids, and tissue arginase levels were examined as outcome parameters after widespread Cre-recombinase activation in a conditional knockout model of arginase 1 deficiency. One hundred percent of adult female and 70 percent of adult male mice died an average of 21.0 and 21.6 days, respectively, after the initiation of tamoxifen administration. Animals demonstrated elevated circulating ammonia and arginine at the onset of phenotypic abnormalities. In addition, brain and liver amino acids demonstrated abnormalities. These studies demonstrate that (a) the absence of arginase in adult animals results in a disease profile (leading to death) similar to that of the targeted knockout and (b) the phenotypic abnormalities seen in the juvenile-onset model are not exclusive to the age of the animal but instead to the biochemistry of the disorder. This adult model will be useful for developing gene- and cell-based therapies for this disorder that will not limited by by the small animal size of neonatal therapy

  6. 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

  7. TLR signaling controls lethal encephalitis in WNV-infected brain.

    PubMed

    Sabouri, Amir H; Marcondes, Maria Cecilia Garibaldi; Flynn, Claudia; Berger, Michael; Xiao, Nengming; Fox, Howard S; Sarvetnick, Nora E

    2014-07-29

    Toll-like receptors (TLRs) are known to be activated in Central Nervous System (CNS) viral infections and are recognized to be a critical component in innate immunity. Several reports state a role for particular TLRs in various CNS viral infections. However, excessive TLR activation was previously reported by us in correlation with a pathogenic, rather than a protective, outcome, in a model of SIV encephalitis. Here we aimed at understanding the impact of TLR-mediated pathways by evaluating the early course of pathogenesis in the total absence of TLR signaling during CNS viral infections. We utilized a mouse model of sublethal West Nile virus (WNV) infection. WNV is an emerging neurotropic flavivirus, and a significant global cause of viral encephalitis. The virus was peripherally injected into animals that simultaneously lacked two key adapter molecules of TLR signaling, MyD88 and TRIF. On day 2 pi (post infection), MyD88/Trif-/- mice showed an increased susceptibility to WNV infection, and revealed an impairment in innate immune cytokines, when compared to wild type mice (WT). By day 6 pi, there was an increase in viral burden and robust expression of inflammatory cytokines as well as higher cell infiltration into the CNS in MyD88/Trif-/-, when compared to infected WT. A drastic increase in microglia activation, astrogliosis, and inflammatory trafficking were also observed on day 6 pi in MyD88/Trif-/-. Our observations show a protective role for TLR signaling pathways in preventing lethal encephalitis at early stages of WNV infection. PMID:24928618

  8. Fentanyl-Laced 'Norco' Is Lethal, Report Warns

    MedlinePlus

    ... fullstory_160158.html Fentanyl-Laced 'Norco' Is Lethal, Report Warns New street drug combines two synthetic opioids ... imprint and were beige instead of white. The report was published online July 27 in the journal ...

  9. 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...

  10. 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 ...

  11. Making Animations

    ERIC Educational Resources Information Center

    Robinson, James

    2007-01-01

    In this article, the author provides simple instructions for making an animation using "PowerPoint". He describes the process by walking readers through it for a sample image. (Contains 1 figure and 1 note.)

  12. 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...

  13. 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)

  14. [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

  15. In vitro breast cancer cell lethality of Brazilian plant extracts.

    PubMed

    Suffredini, I B; Paciencia, M L B; Frana, S A; Varella, A D; Younes, R N

    2007-10-01

    In this study we screened the cytotoxicity of 1220 plant extracts obtained from 351 plants belonging to 74 families occurring in the Amazon and Atlantic rain forests against MCF-7 human breast adenocarcinoma cell lines. All extracts were tested at a dose of 100 microg/mL. Only 11 aqueous or organic extracts belonging to the Annonaceae, Apocynaceae, Araceae, Clusiaceae, Flacourtiaceae, Leguminosae, Olacaceae and Violaceae showed marked lethal activity. Vismia guianensis and Annona hypoglauca extracts showed the greatest lethal activity. PMID:18236788

  16. Perinatal-lethal Gaucher disease presenting as hydrops fetalis

    PubMed Central

    BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

    2015-01-01

    Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis. PMID:26327947

  17. Late-acting dominant lethal genetic systems and mosquito control

    PubMed Central

    Phuc, Hoang Kim; Andreasen, Morten H; Burton, Rosemary S; Vass, Céline; Epton, Matthew J; Pape, Gavin; Fu, Guoliang; Condon, Kirsty C; Scaife, Sarah; Donnelly, Christl A; Coleman, Paul G; White-Cooper, Helen; Alphey, Luke

    2007-01-01

    Background Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. Results We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conclusion Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease

  18. Atlas 2 Animation

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Atmospheric Laboratory for Applications and Science-2 (ATLAS-2), was designed to collect data on the relationship between the sun's energy output and Earth's middle atmosphere and how these factors affect the ozone layer. The ATLAS-2 flew on the Space Shuttle Discovery's mission SST-56, launched on April 8, 1993. The videotape consists of an animated tour of the instruments that were included as part of the mission. The first half of the tape shows the various instruments, pointing to each in turn and identifying each by the associated initialisms. The instruments identified were: the Atmospheric Trace Molecule Spectroscopy (ATMOS), Millimeter Wave Atmospheric Sounder (MAS), Shuttle Solar Backscatter Ultraviolet/A (SSBUV/A) spectrometer, Solar Spectrum Measurement (SOLSPEC) instrument, Solar Ultraviolet Irradiance Monitor (SUSIM), Active Cavity Radiometer (ACR) and Solar Constant (SOLCON).) The second half of the animation shows the same tour without the pointing or the identification of the instruments.

  19. 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)

  20. 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. PMID:26803999

  1. Method of reliable determination of minimal lethal antibiotic concentrations.

    PubMed Central

    Pearson, R D; Steigbigel, R T; Davis, H T; Chapman, S W

    1980-01-01

    The lack of a standardized, statistically reliable method for in vitro determinations of the minimal lethal or bactericidal concentrations of antibiotics has complicated analyses of isolates of Staphylococcus aureus which appear to be inhibited but not killed by the usual concentrations of cell wall-active antibiotics. We describe a method which identifies some of the covariants involved in determinations of minimal lethal concentrations. Lethality was defined as a 99.9% reduction in the initial inoculum of bacteria after 24 h of incubation. We limited the sample volume to 0.01 ml to minimize the inhibitory effect of antibiotic and corresponding rejection values, which detected lethality with a high degree of sensitivity and specificity. When the number of colonies on subculture was equal to or less than the rejection value, the antibiotic was considered lethal for the test organism. Rejection values encompassed initial inocula from 10(5) to 10(7) colony-forming units per ml for single and duplicate samples and allowed for 1 or 5% variability in pipette volumes and errors in initial inoculum determinations. This method was used to determine the minimal lethal concentrations of semi-synthetic penicillins for S. aureau isolates, one of which was tolerant to the killing action of penicillin. Images PMID:7447427

  2. 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

  3. Variation in lethality and effects of two Australian chirodropid jellyfish venoms in fish.

    PubMed

    Kintner, Anna H; Seymour, Jamie E; Edwards, Susan L

    2005-11-01

    The North Queensland chirodropid box jellyfish Chironex fleckeri and Chiropsalmus sp. share similar nematocyst composition and the same prey of Acetes australis shrimps in their early medusa stages; however, as C. fleckeri individuals reach larger size, the animals add fish to their diet and their complement of nematocyst types changes, allowing larger doses of venom to be delivered to prey. This study demonstrated that the venoms of the two species differ as well: despite similar effects previously documented in crustacean prey models, the two had widely different cardiac and lethal effects in fish, with C. fleckeri being substantially more potent in its ability to cause death. Comparisons between the venom delivery abilities of the two species showed that the change in nematocysts of C. fleckeri cannot alone account for its ontogenetic shift to prey fish; instead, its prey ecology clearly necessitates it having venom capable of acting efficiently to cause death in fish. Although this venom is almost certainly produced at greater metabolic cost to the animal than the less-lethal venom of Chiropsalmus sp., owing to its greater molecular protein complexity, it confers the advantage of increased caloric intake from fish prey, facilitating larger size and potentially greater reproductive output of C. fleckeri over Chiropsalmus sp. PMID:16165181

  4. 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.

  5. Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

    PubMed Central

    Akudugu, John M.; Azzam, Edouard I.; Howell, Roger W.

    2013-01-01

    Purpose This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with 125I-labeled 5-iodo-2′-deoxyuridine (125IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold. Cultures were pulse-labeled for 3 h with 125IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2′-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT® EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with 125IdU/EdU. Additional aliquots were used to determine the mean 125I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA-MB-231 cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions These studies demonstrate the capacity of 125IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype. PMID:22489958

  6. Trehalose dimycolate enhances resistance to infection in neutropenic animals.

    PubMed

    Madonna, G S; Ledney, G D; Elliott, T B; Brook, I; Ulrich, J T; Myers, K R; Patchen, M L; Walker, R I

    1989-08-01

    Bacterial infections are lethal complications of neutropenia, and antibiotics alone are inadequate therapy for these infections. Irradiated mice become severely neutropenic and remain susceptible to infection for 2 to 3 weeks, depending on the dose and quality of radiation. Some bacterial cell wall derivatives stimulate nonspecific host defense mechanisms against a variety of microbes which might cause postirradiation infection. In this study we determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance survival in mice when given before or after lethal doses of 60Co radiation and (ii) increase nonspecific resistance to postirradiation infection. Treatment with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced survival before and after lethal doses of 60Co irradiation. This result correlated with the ability of TDM to reduce the translocation of intestinal bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance to infection, TDM injected 1 h after sublethal irradiation increased resistance to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K. pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K. pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated mice to overcome infection. However, TDM treatment 1 h postirradiation combined with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even when the higher dose of bacteria (5,000 LD50/30) was used. These results indicate that in irradiated mice, TDM can be used to enhance survival and, as a potent stimulant of nonspecific resistance to infection in neutropenic mice, can act synergistically with antibiotic therapy to reduce sepsis and mortality. PMID:2663726

  7. Recombinant human thrombopoietin promotes hematopoietic reconstruction after severe whole body irradiation

    PubMed Central

    Wang, Chao; Zhang, Bowen; Wang, Sihan; Zhang, Jing; Liu, Yiming; Wang, Jingxue; Fan, Zeng; Lv, Yang; Zhang, Xiuyuan; He, Lijuan; Chen, Lin; Xia, Huanzhang; Li, Yanhua; Pei, Xuetao

    2015-01-01

    Recombinant human thrombopoietin (rHuTPO) is a drug that is used clinically to promote megakaryocyte and platelet generation. Here, we report the mitigative effect of rHuTPO (administered after exposure) against severe whole body irradiation in mice. Injection of rHuTPO for 14 consecutive days following exposure significantly improved the survival rate of lethally irradiated mice. RHuTPO treatment notably increased bone marrow cell density and LSK cell numbers in the mice after sub-lethal irradiation primarily by promoting residual HSC proliferation. In lethally irradiated mice with hematopoietic cell transplantation, rHuTPO treatment increased the survival rate and enhanced hematopoietic cell engraftment compared with the placebo treatment. Our observations indicate that recombinant human TPO might have a therapeutic role in promoting hematopoietic reconstitution and HSC engraftment. PMID:26403418

  8. Metalloproteinase Inhibitors, Nonantimicrobial Chemically Modified Tetracyclines, and Ilomastat Block Bacillus anthracis Lethal Factor Activity in Viable Cells

    PubMed Central

    Kocer, Salih S.; Walker, Stephen G.; Zerler, Brad; Golub, Lorne M.; Simon, Sanford R.

    2005-01-01

    Lethal toxin, produced by the bacterium Bacillus anthracis, is a major contributor to morbidity and mortality in animals and humans who have contracted anthrax. One component of this toxin, lethal factor (LF), proteolytically inactivates members of the mitogen-activated protein kinase kinase (MAPKK or MEK) family. In this study we show that CMT-300, CMT-308, and Ilomastat, agents initially characterized as matrix metalloproteinase inhibitors which are in early stages of development as pharmaceuticals, effectively inhibit the zinc metalloproteinase activity of LF. All three inhibitors, CMT-300, CMT-308, and Ilomastat, inhibit LF-mediated cleavage of a synthetic peptide substrate based on the N-terminal domain of MEKs. Inhibition of LF-mediated MEK proteolysis by all three agents was also achieved using lysates of the human monocytoid line MonoMac 6 as sources of MAPKKs and visualization of the extent of cleavage after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by detection by Western blotting. Finally, we have demonstrated inhibition of intracellular MEKs in viable human monocytes and MonoMac 6 cells by these agents after incubation of the cells with a reconstituted preparation of recombinant lethal toxin. All three agents are effective inhibitors when incubated with LF prior to exposure to cells, while the CMTs, but not Ilomastat, are also effective when added after LF has already entered the viable cell targets. These results offer promise for strategies to combat effects of the lethal toxin of B. anthracis. PMID:16239558

  9. Dissecting the Contributions of Clostridium perfringens Type C Toxins to Lethality in the Mouse Intravenous Injection Model

    PubMed Central

    Fisher, Derek J.; Fernandez-Miyakawa, Mariano E.; Sayeed, Sameera; Poon, Rachael; Adams, Victoria; Rood, Julian I.; Uzal, Francisco A.; McClane, Bruce A.

    2006-01-01

    The gram-positive anaerobe Clostridium perfringens produces a large arsenal of toxins that are responsible for histotoxic and enteric infections, including enterotoxemias, in humans and domestic animals. C. perfringens type C isolates, which cause rapidly fatal diseases in domestic animals and enteritis necroticans in humans, contain the genes for alpha toxin (plc), perfringolysin O (pfoA), beta toxin (cpb), and sometimes beta2 toxin (cpb2) and/or enterotoxin (cpe). Due to the economic impact of type C-induced diseases, domestic animals are commonly vaccinated with crude type C toxoid (prepared from inactivated culture supernatants) or bacterin/toxoid vaccines, and it is not clear which toxin(s) present in these vaccines actually elicits the protective immune response. To improve type C vaccines, it would be helpful to assess the contribution of each toxin present in type C supernatants to lethality. To address this issue, we surveyed a large collection of type C isolates to determine their toxin-producing abilities. When late-log-phase vegetative culture supernatants were analyzed by quantitative Western blotting or activity assays, most type C isolates produced at least three lethal toxins, alpha toxin, beta toxin, and perfringolysin O, and several isolates also produced beta2 toxin. In the mouse intravenous injection model, beta toxin was identified as the main lethal factor present in type C late-log-phase culture supernatants. This conclusion was based on monoclonal antibody neutralization studies and regression analyses in which the levels of alpha toxin, beta toxin, perfringolysin O, and beta2 toxin production were compared with lethality. Collectively, our results highlight the importance of beta toxin for type C-induced toxemia. PMID:16926413

  10. Consequences of lethal-whole-body gamma radiation and possible ameliorative role of melatonin.

    PubMed

    Mihandoost, Ehsan; Shirazi, Alireza; Mahdavi, Seied Rabie; Aliasgharzadeh, Akbar

    2014-01-01

    Gamma radiation induces the generation of free radicals, leading to serious cellular damages in biological systems. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the deleterious effects of radiation. Melatonin synergistically acts as an immune-stimulator and antioxidant. We investigated the possible radioprotective role of melatonin (100 mg/kg i.p.) against lethal-whole-body radiation- (10 Gy) induced sickness, body weight loss, and mortality in rats. Results of the present study suggest that exposure to lethal-whole-body radiation incurred mortality, body weight loss, and apoptosis and it also depleted the immunity and the antioxidant status of the rats. Our results show that melatonin pretreatment provides protection against radiation induced mortality, oxidative stress, and immune-suppression. The melatonin pretreated irradiated rats showed less change in body weight as compared to radiation only group. On the other hand, melatonin appeared to have another radioprotective role, suggesting that melatonin may reduce apoptosis through a caspase-3-mediated pathway by blocking caspase-3 activity. PMID:25431791

  11. Consequences of Lethal-Whole-Body Gamma Radiation and Possible Ameliorative Role of Melatonin

    PubMed Central

    Mihandoost, Ehsan; Shirazi, Alireza; Mahdavi, Seied Rabie; Aliasgharzadeh, Akbar

    2014-01-01

    Gamma radiation induces the generation of free radicals, leading to serious cellular damages in biological systems. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the deleterious effects of radiation. Melatonin synergistically acts as an immune-stimulator and antioxidant. We investigated the possible radioprotective role of melatonin (100 mg/kg i.p.) against lethal-whole-body radiation- (10 Gy) induced sickness, body weight loss, and mortality in rats. Results of the present study suggest that exposure to lethal-whole-body radiation incurred mortality, body weight loss, and apoptosis and it also depleted the immunity and the antioxidant status of the rats. Our results show that melatonin pretreatment provides protection against radiation induced mortality, oxidative stress, and immune-suppression. The melatonin pretreated irradiated rats showed less change in body weight as compared to radiation only group. On the other hand, melatonin appeared to have another radioprotective role, suggesting that melatonin may reduce apoptosis through a caspase-3-mediated pathway by blocking caspase-3 activity. PMID:25431791

  12. 76 FR 6054 - Use of Less-Than-Lethal Force: Delegation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-03

    ... proposed on June 25, 2008 (73 FR 39584), regarding the use of ] chemical agents and other less-than-lethal... of Prisons 28 CFR Part 552 RIN 1120-AB46 Use of Less-Than-Lethal Force: Delegation AGENCY: Bureau of... its proposed regulation on the use of chemical agents and other non-lethal (less-than-lethal) force...

  13. 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

  14. Adapting Animals.

    ERIC Educational Resources Information Center

    Wedman, John; Wedman, Judy

    1985-01-01

    The "Animals" program found on the Apple II and IIe system master disk can be adapted for use in the mathematics classroom. Instructions for making the necessary changes and suggestions for using it in lessons related to geometric shapes are provided. (JN)

  15. Animal Bioacoustics

    NASA Astrophysics Data System (ADS)

    Fletcher, Neville

    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 whole-system behavior. This latter is the approach to be adopted here.

  16. 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.…

  17. 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)

  18. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation.

    PubMed

    Huang, Eng-Yen; Wang, Feng-Sheng; Chen, Yu-Min; Chen, Yi-Fan; Wang, Chung-Chi; Lin, I-Hui; Huang, Yu-Jie; Yang, Kuender D

    2014-10-30

    Amifostine (AM) is a radioprotector that scavenges free radicals and is used in patients undergoing radiotherapy. p53 has long been implicated in cell cycle arrest for cellular repair after radiation exposure. We therefore investigated the protective p53-dependent mechanism of AM on small bowel damage after lethal whole-abdominal irradiation (WAI). AM increased both the survival rate of rats and crypt survival following lethal 18 Gy WAI. The p53 inhibitor PFT-α compromised AM-mediated effects when administered prior to AM administration. AM significantly increased clonogenic survival in IEC-6 cells expressing wild type p53 but not in p53 knockdown cells. AM significantly increased p53 nuclear accumulation and p53 tetramer expression before irradiation through the inhibition of p53 degradation. AM inhibited p53 interactions with MDM2 but enhanced p53 interactions with 14-3-3σ. Knockdown of 14-3-3σ also compromised the effect of AM on clonogenic survival and p53 nuclear accumulation in IEC-6 cells. For the first time, our data reveal that AM alleviates lethal small bowel damage through the induction of 14-3-3σ and subsequent accumulation of p53. Enhancement of the p53/14-3-3σ interaction results in p53 tetramerization in the nucleus that rescues lethal small bowel damage. PMID:25230151

  19. ACUTE TOXICITY AND BIOCONCENTRATION OF ENDOSULFAN-EXPOSED ESTUARINE ANIMALS

    EPA Science Inventory

    Acute (96-h) flow-through toxicity tests with endosulfan (Thiodan) were conducted with several estuarine animals. The test species and their 96-h lethal concentration for 50 percent of the organisms (LC50) values were: pink shrimp (Penaeus duorarum), 0.04 micrograms/litre; grass ...

  20. 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

  1. [Dangerous animals].

    PubMed

    Hasle, Gunnar

    2002-06-30

    As travellers seek ever more exotic destinations they are more likely to encounter dangerous animals. Compared to risks such as AIDS, traffic accidents and malaria, the risk is not so great; many travellers are, however, concerned about this and those who give pre-travel vaccines and advice should know something about it. This article is mainly based on medical and zoological textbooks. Venomous stings and bites may be prevented by adequate clothing and by keeping safe distance to the animals. Listening to those who live in the area is of course important. Travellers should not carry antisera with them, but antisera should be available at local hospitals. It should be borne in mind that plant eaters cause just as many deaths as large predators. In some cases it is necessary to carry a sufficiently powerful firearm. PMID:12555616

  2. 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

  3. An Antivector Vaccine Protects against a Lethal Vector-Borne Pathogen

    PubMed Central

    Labuda, Milan; Trimnell, Adama R; Ličková, Martina; Kazimírová, Mária; Davies, Gillian M; Lissina, Olga; Hails, Rosie S; Nuttall, Patricia A

    2006-01-01

    Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP) of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV) transmitted by infected Ixodes ricinus ticks. The vaccine has a “dual action” in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: “transmission,” number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; “support,” number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and “survival,” number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD) that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site. PMID:16604154

  4. 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

  5. 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

  6. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    PubMed

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V

    1991-06-01

    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described. PMID:1863995

  7. Approaches to identifying synthetic lethal interactions in cancer.

    PubMed

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

    2015-06-01

    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

  8. Advantages of less-tech, less-than-lethal technologies

    NASA Astrophysics Data System (ADS)

    Marts, Donna J.; Overlin, Trudy K.

    1995-05-01

    This paper illustrates the advantages of developing less-tech technologies by reporting on two less-tech, less-than-lethal prototype law enforcement tools developed at the Idaho National Engineering Laboratory. The devices were developed for the National Institute of Justice, less- than-lethal weapons program: 1) an air bag restraint device for use in restraining suspects who become violent during transport in patrol vehicles, and 2) a retractable spiked barrier strip for stopping fleeing vehicles during high-speed pursuit. The success of both projects relied on developing design requirements in conjunction with the actual users of the devices.

  9. 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

  10. 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

  11. 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

  12. 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. PMID:26438506

  13. Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset

    PubMed Central

    Feldmann, Friederike; Rasmussen, Angela L.; Okumura, Atsushi; Peng, Xinxia; Thomas, Matthew J.; van Doremalen, Neeltje; Haddock, Elaine; Nagy, Lee; LaCasse, Rachel; Liu, Tingting; Zhu, Jiang; McLellan, Jason S.; Scott, Dana P.; Katze, Michael G.; Feldmann, Heinz; Munster, Vincent J.

    2014-01-01

    The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies. PMID:25144235

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

    PubMed Central

    Negus, David; Vipond, Julia; Hatch, Graham J.; Rayner, Emma L.

    2015-01-01

    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. PMID:26438506

  15. 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

  16. 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

  17. 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.

  18. Bromobenzene-induced lethal toxicity in mouse is prevented by pretreatment with zinc sulfate.

    PubMed

    Yoshioka, Hiroki; Fukaya, Shiori; Fukuishi, Nobuyuki; Nagatsu, Akito; Nonogaki, Tsunemasa; Onosaka, Satomi

    2016-07-25

    In the current study, we evaluated the protective effect of zinc (Zn) against bromobenzene (BB) -induced lethal toxicity. We used Zn because this element is known to be an inducer of metallothionein (MT), which is in turn known to serve as an endogenous scavenger of free radicals. We administered Zn (as ZnSO4) at 50 mg/kg subcutaneously once-daily for 3 successive days prior to a single intraperitoneal administration of 1.2 g/kg BB in male ddY mice. Our results showed that pretreatment with Zn completely abolished the BB-induced mortality of mice until 48 h. We also found that pretreatment of mice with Zn significantly decreased the functional marker levels and reduced the histological damage both in liver and kidney as assessed at 18 h post-BB. We also showed that pretreatment with Zn enhanced antioxidative activity, resulting in decreased lipid peroxidation in both liver and kidney. Moreover, BB-induced calcium levels were downregulated by pretreatment with Zn. In addition, Zn-induced MT was decreased in Zn + BB-treated animals, implying that MT was consumed by BB-induced radicals. These findings suggest that prophylaxis with Zn protects mice from BB-induced lethal toxicity by decreasing oxidative stress in liver and kidney, presumably by induction of MT, which scavenges radicals induced by BB exposure. PMID:27270452

  19. 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.

  20. 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. PMID:26792728

  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. PMID:26687352

  2. 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

  3. 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…

  4. Lethal head entrapment--a problem characteristic of early childhood.

    PubMed

    Byard, Roger W; Charlwood, Cheryl

    2009-08-01

    Accidental deaths in infancy and early childhood often result from young childrens' lack of understanding of the dangers of certain situations and their physical inability to extricate themselves from potentially lethal circumstances. Two cases are reported to demonstrate an age-related susceptibility in the young to lethal head entrapment. Case 1: a 5-month-old girl smothered when she slipped down in her stroller, trapping her head beneath the frame and forcing her face into the soft material of the base. Case 2: a 14-month-old boy was hanged while exploring a filing cabinet when his head became caught between two lower drawers. Additional mental and physical characteristics that predispose young children and infants to lethal head entrapment include an inability to effectively problem solve once confronted with a hazardous situation, and relatively large heads and weak neck musculature. Because of these features lethal head entrapment represents a particular circumstance that may predispose to accidental asphyxial deaths in the very young. A combination of careful death scene and autopsy evaluations will be required to confirm the alleged circumstances of death in these cases, including mortuary re-enactments and assessment of the deceased infant's level of physical maturity and mobility. PMID:19573845

  5. 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.

  6. 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…

  7. 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…

  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. 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

  10. 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...

  11. Moving ahead on harnessing synthetic lethality to fight cancer

    PubMed Central

    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. PMID:27308440

  12. 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

  13. A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission.

    PubMed

    Swinton, J; Tuyttens, F; MacDonald, D; Nokes, D J; Cheeseman, C L; Clifton-Hadley, R

    1997-05-29

    In this paper we use mathematical modelling to consider the broad advantages and disadvantages of fertility control over lethal control for bovine tuberculosis in badger populations. We use a deliberately simple model, attempting to capture only the key transmission processes. The model is parametrized with reference to the long-term Woodchester Park study. Estimates of mortality rate from this study suggest no significant extra mortality risk for animals with evidence of infection as indicated by the presence of anti-Mycobacterium bovis antibodies or M. bovis isolation. We find that large reductions in prevalence are sometimes the consequence of only moderate reductions in population numbers. If we assume that the act of control does not in itself affect transmission rates, then as far as eradication is concerned, both fertility control and mortality control operate through the same epidemiological mechanism, the removal of susceptibles: if one is in principle capable of keeping a population low enough to be infection free then so is the other. It is necessary to continue either form of control at regular intervals to maintain a constant level of infection in the long term. If control were to be stopped, return to precontrol levels of badger population and infection prevalence would be expected within a few years. Fertility control is less effective in reducing population density than lethal control since it can only act, at maximum, to remove one age cohort per year. It is also less effective in reducing transmission as it can only ever remove susceptibles, while lethal control also removes infectious badgers. However, if the social disturbance caused by lethal control does in fact increase contact rates for the remaining infectious badgers, the relative efficacies of the two strategies become a great deal less clear. While we have no quantitative data on the extent to which social perturbation does act to promote transmission, model simulations show that it is

  14. 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

  15. Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.

    PubMed

    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

  16. Annotating novel genes by integrating synthetic lethals and genomic information

    PubMed Central

    Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

    2008-01-01

    Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

  17. 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

  18. Myxoma virus expressing interleukin-15 fails to cause lethal myxomatosis in European rabbits.

    PubMed

    Liu, Jia; Wennier, Sonia; Reinhard, Mary; Roy, Edward; MacNeill, Amy; McFadden, Grant

    2009-06-01

    Myxoma virus (MYXV) is a poxvirus pathogenic only for European rabbits, but its permissiveness in human cancer cells gives it potential as an oncolytic virus. A recombinant MYXV expressing both the tdTomato red fluorescent protein and interleukin-15 (IL-15) (vMyx-IL-15-tdTr) was constructed. Cells infected with vMyx-IL-15-tdTr secreted bioactive IL-15 and had in vitro replication kinetics similar to that of wild-type MYXV. To determine the safety of this virus for future oncolytic studies, we tested its pathogenesis in European rabbits. In vivo, vMyx-IL-15-tdTr no longer causes lethal myxomatosis. Thus, ectopic IL-15 functions as an antiviral cytokine in vivo, and vMyx-IL-15-tdTr is a safe candidate for animal studies of oncolytic virotherapy. PMID:19279088

  19. 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

  20. 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

  1. Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

    SciTech Connect

    Azuma, E.; Yamamoto, H.; Kaplan, J. )

    1989-09-01

    Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients.

  2. [Food irradiation].

    PubMed

    Migdał, W

    1995-01-01

    A worldwide standard on food irradiation was adopted in 1983 by Codex Alimentarius Commission of the Joint Food Standard Programme of the Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO). As a result, 41 countries have approved the use of irradiation for treating one or more food items and the number is increasing. Generally, irradiation is used to: food loses, food spoilage, disinfestation, safety and hygiene. The number of countries which use irradiation for processing food for commercial purposes has been increasing steadily from 19 in 1987 to 33 today. In the frames of the national programme on the application of irradiation for food preservation and hygienization an experimental plant for electron beam processing has been established in Institute of Nuclear Chemistry and Technology. The plant is equipped with a small research accelerator Pilot (19MeV, 1 kW) and an industrial unit Elektronika (10MeV, 10 kW). On the basis of the research there were performed at different scientific institutions in Poland, health authorities have issued permission for irradiation for: spices, garlic, onions, mushrooms, potatoes, dry mushrooms and vegetables. PMID:8619113

  3. 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.

  4. Animal Intuitions.

    PubMed

    Kaebnick, Gregory E

    2016-07-01

    As described by Lori Gruen in the Perspective column at the back of this issue, federally supported biomedical research conducted on chimpanzees has now come to an end in the United States, although the wind-down has taken longer than expected. The process began with a 2011 Institute of Medicine report that set up several stringent criteria that sharply limited biomedical research. The National Institutes of Health accepted the recommendations and formed a committee to determine how best to implement them. The immediate question raised by this transition was whether the IOM restrictions should be extended in some form to other nonhuman primates-and beyond them to other kinds of animals. In the lead article in this issue, Anne Barnhill, Steven Joffe, and Franklin Miller consider the status of other nonhuman primates. PMID:27417859

  5. Antibodies against recombinant catalytic domain of lethal toxin of Clostridium sordellii neutralize lethal toxin toxicity in HeLa cells.

    PubMed

    Arya, Preetika; Ponmariappan, S; Singh, Lokendra; Prasad, G B K S

    2013-02-01

    Lethal toxin of Clostridium sordellii (MLD 150 ng/kg) is one of the most potent Clostridial toxins and is responsible for most of the diseases including sudden death syndrome in cattle, sheep and toxic shock syndrome, necrotizing faciitis, neonatal omphalitis and gangrene in humans. Lethal toxin (TcsL) is a single chain protein of about 270 kDa. In the present study, 1.6 kb DNA fragment encoding for the catalytic domain of TcsL was PCR amplified, cloned in pQE30 UA vector and expressed in E. coli SG 13009. The expression of recombinant lethal toxin protein (rTcsL) was optimized and it was purified under native conditions using a single step Ni-NTA affinity chromatography. The purified recombinant protein was used for the production of polyclonal antibodies in mice and rabbit. The raised antibodies reacted specifically with the purified rTcsL and intact native lethal toxin on Western blot. The biological activity of the recombinant protein was tested in HeLa cells where it showed the cytotoxicity. Further, the polyclonal antibodies were used for in-vitro neutralization of purified rTcsL, acid precipitated C. sordellii and C. difficile native toxins in HeLa cells. Mice and rabbit anti-rTcsL sera effectively neutralized the cytotoxicity of rTcsL and C. sordellii native toxin but it did not neutralize the cytotoxicity of C. difficile toxin in HeLa cells. PMID:22894159

  6. Lethal challenge of gnotobiotic weanling rats with bacterial isolates from cases of sudden infant death syndrome (SIDS).

    PubMed

    Lee, S; Barson, A J; Drucker, D B; Morris, J A; Telford, D R

    1987-12-01

    An attempt was made to produce an animal model of sudden infant death syndrome (SIDS). The experimental animals (germ free weanling rats) were exposed to nasopharyngeal isolates from cases of SIDS to test the hypothesis that common bacteria may have an aetiological role in the disease. Negative results were obtained when the strains were tested in isolation, but certain combinations of organisms (specifically some Staphylococcus aureus and Escherichia coli) killed the animals rapidly (less than 18 hours) without prolonged terminal illness. Post mortem histological findings were consistent with those of SIDS. The lethal toxigenic potential of nasopharyngeal bacteria, which are regarded as harmless in adults, should be reconsidered in respect of the aetiology of SIDS. PMID:3323245

  7. Uptake of indium-111-labeled platelets and indium-111 oxine by murine kidneys after total-body irradiation

    SciTech Connect

    Ebbe, S.; Taylor, S.; Maurer, H.; Kullgren, B.

    1996-08-01

    Radiation nephropathy is a well-known late manifestation of renal irradiation in human beings and experimental animals. Its pathogenesis is unclear, but vascular injury may play a role. Endothelial cells have been demonstrated to manifest a variety of abnormalities within hours of exposure to radiation. In the present experiments mice were exposed to lethal doses of whole-body radiation, and the distribution of {sup 111}In-labeled platelets was evaluated during the first week after irradiation. The purpose was to determine if early abnormalities of endothelial cells would be manifested by altered sequestration of platelets in kidneys and other organs. It was found that the indium accumulated in the kidneys of irradiated mice to a greater extent than in nonirradiated mice, but the pattern of accumulation differed from that seen after injection of radiolabeled platelets. Renal hyperemia was not demonstrable with {sup 51}Cr-labeled red cells, renal vascular permeability was not detected with {sup 125}I-labeled albumin, and the pattern of renal uptake of plasma proteins labeled albumin, and the pattern of renal uptake of plasma proteins labeled with {sup 59}Fe {sup 111}In did not coincide with that seen from {sup 111}In administered as labeled platelets or oxine. Renal uptake of {sup 111}In-oxine was not associated with alterations in urinary or fecal excretion or an increase in total-body retention of the radioisotope. The findings are consistent with the notion that renal vascular injury at the time of irradiation results in accumulation of platelets or platelet constituents during the first week after total-body irradiation of mice. 29 refs., 5 figs., 3 tabs.

  8. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis.

    PubMed Central

    Drake, T. A.; Cheng, J.; Chang, A.; Taylor, F. B.

    1993-01-01

    Disseminated intravascular thrombosis is a frequent complication of endotoxic shock, and modulation of endothelial cell hemostatic properties has been proposed to play a role in its pathogenesis based on studies of endothelial cells in culture. This study examined the in vivo expression of tissue factor (TF) and thrombomodulin (TM) in a baboon model of lethal Escherichia coli sepsis using immunohistochemistry with monospecific antibodies. Expression of E-selectin (E-sel) was also determined as a marker of endothelial cell activation. Correlation of immunoreactivity with procoagulant activity in lipopolysaccharide-stimulated cultured human endothelial cells showed that immunohistochemistry was sufficiently sensitive to detect as little as 5% of the maximum in vitro endothelial cell TF response. Vascular endothelium of control animals expressed TM but had no detectable TF or E-sel. Following E. coli infusion, widespread E-sel expression and microvascular fibrin deposition was evident within 6 hours. However, expression of TF by endothelial cells became detectable only in the splenic microvasculature, where endothelial specificity of TF expression was confirmed by dual immunofluorescence of TF with von Willebrand's factor and with TM. In the spleen, there was a dissociation of expression of TF and E-sel, with marginal zone vessels being TF-positive and E-sel-negative, whereas sinusoidal endothelium was E-sel-positive but TF-negative. TM expression was unchanged from controls. Additionally, expression of TF by lung alveolar epithelial cells, splenic macrophages, and epithelial cells of the renal glomeruli was observed to be enhanced in septic animals. This study documents endothelial cell expression of TF in vivo in a relevant pathological setting. At the same time, compared with endothelial cells in culture, there is in vivo both significantly greater control of TF expression than expected, given the strong positive stimuli present in lethal E. coli septic shock and

  9. Constitutive MEK1 activation rescues anthrax lethal toxin-induced vascular effects in vivo.

    PubMed

    Bolcome, Robert E; Chan, Joanne

    2010-12-01

    Anthrax lethal toxin (LT) increases vascular leakage in a number of mammalian models and in human anthrax disease. Using a zebrafish model, we determined that vascular delivery of LT increased permeability, which was phenocopied by treatment with a selective chemical inhibitor of MEK1 and MEK2 (also known as mitogen-activated protein kinase [MAPK] kinase, MEK, or MKK). Here we investigate further the role of MEK1/phospho-ERK (pERK) in the action of LT. Overexpression of wild-type zebrafish MEK1 at high levels did not induce detrimental effects. However, a constitutively activated version, MEK1(S219D,S223D) (MEK1DD), induced early defects in embryonic development that correlated with increased ERK/MAPK phosphorylation. To bypass these early developmental defects and to provide a genetic tool for examining the action of lethal factor (LF), we generated inducible transgenic zebrafish lines expressing either wild-type or activated MEK1 under the control of a heat shock promoter. Remarkably, induction of MEK1DD transgene expression prior to LT delivery prevented vascular damage, while the wild-type MEK1 line did not. In the presence of both LT and MEK1DD transgene expression, cardiovascular development and function proceeded normally in most embryos. The resistance to microsphere leakage in transgenic animals demonstrated a protective role against LT-induced vascular permeability. A consistent increase in ERK phosphorylation among LT-resistant MEK1DD transgenic animals provided additional confirmation of transgene activation. These findings provide a novel genetic approach to examine mechanism of action of LT in vivo through one of its known targets. This approach may be generally applied to investigate additional pathogen-host interactions and to provide mechanistic insights into host signaling pathways affected by pathogen entry. PMID:20855511

  10. 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

  11. (Molecular basis of the mutagenic and lethal effects of ultraviolet irradiation): Progress report

    SciTech Connect

    Not Available

    1988-01-01

    Studies on the molecular mechanisms by which Escherichia Coli and Micrococcus luteus repair pyrimidine dimers induced in their DNA by ultraviolet light are reported. The studies involve the isolation and enzymatic activity of the ucr system. The specific roles of ucr A and ucr B proteins are sought. In addition the expression of the ucr genes in mammalian cells is addressed. 35 refs. (DT)

  12. 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)

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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. PMID:23664009

  19. 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...

  20. 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.

  1. Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

    PubMed Central

    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

    2007-01-01

    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 (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ( γδ) 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 (μMT) 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+ T cells are required for protection. PMID:17610927

  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. PMID:4092617

  3. Animating Brains.

    PubMed

    Borck, Cornelius

    2016-07-01

    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

  4. 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

  5. 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.

  6. Surviving lethal septic shock without fluid resuscitation in a rodent model

    PubMed Central

    Li, Yongqing; Liu, Baoling; Fukudome, Eugene Y.; Kochanek, Ashley R.; Finkelstein, Robert A.; Chong, Wei; Jin, Guang; Lu, Jennifer; deMoya, Marc A.; Velmahos, George C.; Alam, Hasan B.

    2016-01-01

    Background We have recently demonstrated that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, before a lethal dose of lipopolysaccharide (LPS) improves survival in mice. The purpose of the present study was to determine whether SAHA treatment would attenuate LPS-induced shock and improve survival when given postinsult in a rodent model. Methods C57BL/6J mice were intraperitoneally (IP) injected with LPS (30 mg/kg), and 2 hours later randomized into 2 groups: (1) vehicle animals (n = 10) received dimethyl sulfoxide (DMSO) solution only; and (2) SAHA animals (n = 10) were given SAHA (50 mg/kg, IP) in DMSO solution. Survival was monitored over the next 7 days. In a second study, LPS-injected mice were treated with either DMSO or SAHA as described, and normal (sham) animals served as controls. Lungs were harvested at 4, 6, and 8 hours after LPS injection for analysis of gene expression. In addition, RAW264.7 mouse macrophages were cultured to assess the effects of SAHA post-treatment on LPS-induced inflammation using enzyme-linked immunosorbent assay. Results All LPS-injected mice that received the vehicle agent alone died within 24 hours, whereas the SAHA-treated animals displayed a significant improvement in 1 week survival (80% vs 0%; P < .001). LPS insult significantly enhanced gene expression of MyD88, tumor necrosis factor (TNF)-α and interleukin (IL)-6, and was associated with an increased protein secretion of TNF-α and IL-6 into the cell culture medium. In contrast, SAHA treatment significantly attenuated all of these LPS-related alterations. Conclusion We report for the first time that administration of SAHA (50 mg/kg IP) after a lethal dose of LPS significantly improves long-term survival, and attenuates expression of the proinflammatory mediators TNF-α and IL-6. Furthermore, our data suggest that the anti-inflammatory effects of SAHA may be due to downregulation of the MyD88-dependent pathway, and decreased

  7. The Somatostatin Analog SOM230 (Pasireotide) Ameliorates Injury of the Intestinal Mucosa and Increases Survival after Total-Body Irradiation by Inhibiting Exocrine Pancreatic Secretion

    PubMed Central

    Fu, Qiang; Berbée, Maaike; Boerma, Marjan; Wang, Junru; Schmid, Herbert A.; Hauer-Jensen, Martin

    2009-01-01

    Somatostatin analogs ameliorate intestinal injury after localized irradiation. This study investigated whether SOM230, a novel, metabolically stable analog with broad receptor affinity, reduces intestinal injury and lethality in mice exposed to total-body irradiation (TBI). Male CD2F1 mice were exposed to 7–15 Gy TBI. Twice-daily administration of SOM230 (1, 4 or 10 mg/kg per day) or vehicle was started either 2 days before or 4 h after TBI and continued for either 14 or 21 days. Parameters of intestinal and hematopoietic radiation injury, bacterial translocation, and circulating cytokine levels were assessed. Animal survival was monitored for up to 30 days. SOM230 increased survival (P < 0.001) and prolonged survival time (P < 0.001) whether administration was initiated before or after TBI. There was no benefit from administration for 21 compared to 14 days. The survival benefit of SOM230 was completely reversed by co-administration of pancreatic enzymes (P = 0.009). Consistent with the presumed non-cytoprotective mechanism of action, SOM230 did not influence hematopoietic injury or intestinal crypt lethality. However, SOM230 preserved mucosal surface area (P < 0.001) and reduced bacterial translocation in a dose-dependent manner (P < 0.001). Circulating IL-12 levels were reduced in SOM230-treated mice (P = 0.007). No toxicity from SOM230 was observed. SOM230 enhances animal survival whether administration begins before or after TBI; i.e., it is effective both as a protector and as a mitigator. The mechanism likely involves reduction of intraluminal pancreatic enzymes. Because of its efficacy and favorable safety profile, SOM230 is a promising countermeasure against radiation and should undergo further development. PMID:19580476

  8. 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

  9. Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold.

    PubMed

    Perales, Celia; Domingo, Esteban

    2016-01-01

    The concept of error threshold derived from quasispecies theory is at the basis of lethal mutagenesis, a new antiviral strategy based on the increase of virus mutation rate above an extinction threshold. Research on this strategy is justified by several inhibitor-escape routes that viruses utilize to ensure their survival. Successive steps in the transition from an organized viral quasispecies into loss of biologically meaningful genomic sequences are dissected. The possible connections between theoretical models and experimental observations on lethal mutagenesis are reviewed. The possibility of using combination of virus-specific mutagenic nucleotide analogues and broad-spectrum, non-mutagenic inhibitors is evaluated. We emphasize the power that quasispecies theory has had to stimulate exploration of new means to combat pathogenic viruses. PMID:26294225

  10. 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

  11. 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

  12. 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

  13. 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... INSTITUTIONAL MANAGEMENT CUSTODY Use of Force and Application of Restraints on Inmates § 552.25 Use of chemical agents or non-lethal weapons. The Warden may authorize the use of chemical agents or non-lethal...

  14. 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)

  15. 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)

  16. 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

  17. [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

  18. Rabbit Model for Superantigen-Mediated Lethal Pulmonary Disease.

    PubMed

    Strandberg, Kristi L; Rotschafer, Jessica H; Schlievert, Patrick M

    2016-01-01

    Staphylococcus aureus is a highly significant cause of serious human infections in the USA. Many of these illnesses are mediated by interactions between the host immune system and staphylococcal superantigens (SAgs). Several of these severe staphylococcal infections are initiated in the lungs, making this an important site to study. Here, we describe the rabbit model for investigating the role of staphylococcal SAgs in pulmonary-associated lethal infection and intoxication. PMID:26676039

  19. Meckel-Gruber syndrome: A rare and lethal anomaly

    PubMed Central

    Kheir, Abdelmoneim E. M.; Imam, Abdelmutalab; Omer, Ilham M.; Hassan, Ibtsama M.A.; Elamin, Sara A.; Awadalla, Esra A.; Gadalla, Mohammed H.; Hamdoon, Tagwa A.

    2012-01-01

    Meckel-Gruber syndrome is a rare and lethal autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and bilateral dysplastic cystic kidneys. It can be associated with many other conditions. Antenatal ultrasound examination establishes the diagnosis by identifying at least two of the major features described. We describe a female baby who had the typical triad of Meckel-Gruber syndrome and died shortly after birth.

  20. 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

  1. Irradiance gradients

    SciTech Connect

    Ward, G.J. Ecole Polytechnique Federale, Lausanne ); Heckbert, P.S. . School of Computer Science Technische Hogeschool Delft . Dept. of Technical Mathematics and Informatics)

    1992-04-01

    A new method for improving the accuracy of a diffuse interreflection calculation is introduced in a ray tracing context. The information from a hemispherical sampling of the luminous environment is interpreted in a new way to predict the change in irradiance as a function of position and surface orientation. The additional computation involved is modest and the benefit is substantial. An improved interpolation of irradiance resulting from the gradient calculation produces smoother, more accurate renderings. This result is achieved through better utilization of ray samples rather than additional samples or alternate sampling strategies. Thus, the technique is applicable to a variety of global illumination algorithms that use hemicubes or Monte Carlo sampling techniques.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. [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

  7. Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells.

    PubMed

    Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

    2013-01-01

    Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×10(6) cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective "off the shelf" therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia. PMID:23823334

  8. Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

    PubMed Central

    Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

    2013-01-01

    Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×106 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective “off the shelf” therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia. PMID:23823334

  9. 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.

  10. [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. PMID:9807870

  11. 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)

  12. 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

  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. 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.

  16. 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

  17. The mutational landscape of lethal castration-resistant prostate cancer.

    PubMed

    Grasso, Catherine S; Wu, Yi-Mi; Robinson, Dan R; Cao, Xuhong; Dhanasekaran, Saravana M; Khan, Amjad P; Quist, Michael J; Jing, Xiaojun; Lonigro, Robert J; Brenner, J Chad; Asangani, Irfan A; Ateeq, Bushra; Chun, Sang Y; Siddiqui, Javed; Sam, Lee; Anstett, Matt; Mehra, Rohit; Prensner, John R; Palanisamy, Nallasivam; Ryslik, Gregory A; Vandin, Fabio; Raphael, Benjamin J; Kunju, Lakshmi P; Rhodes, Daniel R; Pienta, Kenneth J; Chinnaiyan, Arul M; Tomlins, Scott A

    2012-07-12

    Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC). However, less is known about the role of mutations. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPCs (2.00 per megabase) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1 that define a subtype of ETS gene family fusion-negative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Furthermore, we identified recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with the AR, which is required for AR-mediated signalling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signalling and increases tumour growth. Proteins that physically interact with the AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX (also known as KDM6A) and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signalling deregulated in prostate cancer, and prioritize candidates for future study. PMID

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity

    PubMed Central

    Paldiwal, Ashutosh Abhimanyu; Korday, Charusheela Sujit; Jadhav, Shruti Sudhir

    2015-01-01

    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

  6. [Isadora Duncan syndrome : Lethal strangulation injuries caused by filling equipment].

    PubMed

    Jansen, G; Mertzlufft, F

    2016-05-01

    Aside from suicide attempts or autoerotic accidents, serious injuries from strangulation are rare. In 1929, the accidental death of the famous dancer Isadora Duncan gained high profile. However, even today there are reports of accidental strangulations. These are referred to as Isadora Duncan or long-scarf syndrome and are oftentimes lethal. In the pre-hospital setting, airway management has been challenging, as even a correctly placed airway device may initiate a rapid and marked deterioration of the patient's condition. The case history at hand outlines the death of a 47-year-old female, following entanglement of her scarf in bottling equipment. PMID:27142365

  7. Iliac arterial-enteric fistulas occurring after pelvic irradiation

    SciTech Connect

    Vetto, J.T.; Culp, S.C.; Smythe, T.B.; Chang, A.E.; Sindelar, W.F.; Sugarbaker, P.H.; Heit, H.A.; Giordano, J.M.; Kozloff, L.

    1987-05-01

    Fistulas from the iliac artery to the bowel constitute a condition that is often lethal. Excluding fistulas related to vascular grafts, a review of previously reported cases shows that they are most often due to atherosclerotic iliac aneurysms. Three unusual cases of this condition that occurred after high-dose pelvic irradiation for treatment of cancer are presented; in no case was recurrent tumor evident. These cases suggest that high-dose pelvic irradiation can predispose to the formation of iliac arterial-enteric fistulas, particularly if sepsis or inflammation develops. The definitive surgical management of these fistulas entails bowel resection, arterial ligation, and extra-anatomic bypass.

  8. 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.

  9. [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

  10. 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

  11. 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.

  12. Less-lethal munitions as extended-range impact weapons

    NASA Astrophysics Data System (ADS)

    Hubbs, Ken

    1997-01-01

    With the proliferation of 'suicide by cop' incidents, the concept of less lethal (LL) impact munitions has definitely caught on. There is much to be said for sterile laboratory testing and wound ballistic studies, but having 'real world' operational data is invaluable. Two years ago, a data base was set up to collect this information. The data base continues to grow with incidents from a cross the country and others pursued internationally. Indications are that LL munitions deliver a similar amount of force as conventional police impact weapons i.e., police batons, PR-24's, nunchakus, etc. One advantage over conventional impact weapons, is that LL munitions can be used at much greater distances from a suspect or crown of rioters. This gave rise to the term: extended range impact weapons. Having the ability to examine numerous cases in which these LL munitions have been successfully used for the resolution of critical incidents, is beneficial in evaluating the application and defending the usage of these force options. This paper examines 187 less lethal shootings and discusses such things as: the distance the munitions were fired, the types of injuries sustained by the targeted suspect, the body area of impact, what, if any weapons the suspect was armed with, and the type of incident requiring police response.

  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. 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

  15. Homoeosis in Drosophila: a description of the Polycomb lethal syndrome.

    PubMed

    Denell, R E; Frederick, R D

    1983-05-01

    Adults heterozygous for dominant mutations at the haploabnormal Polycomb (Pc) locus display many homoeotic transformations. E. B. Lewis (1978) first described the cuticular morphology of lethal embryos homozygous for Polycomb mutant alleles, and suggested that the Pc+ gene product acts as a repressor of genes in the Bithorax gene complex. In the present work, we have further examined the Polycomb lethal syndrome by phase-contrast and scanning electron microscopy of whole mounts, and show that the phenotype is more complex than hitherto realized. Many cuticular features characteristic of more anterior body segments are partially or completely transformed to resemble those of more caudal segments; the posteriormost homoeotic features which develop are those of the 8th abdominal segment (rather than the 9th or 10th). Involution and dorsal closure of the head are usually incomplete, and the labium and dorsal head regularly develop cuticular features normally characteristic of abdominal segments. Not all homoeotic alterations are caudal, however, and embryos also display partial transformations of the 9th (or 10th) abdominal segment to 8th and of meso- and metathorax to prothorax. It should be emphasized that Polycomb mutations do not homoeotically transform segments as a whole; various cuticular markers differ considerably in their relative probability and extent of transformation, and a single segment may display features normally specific to several different segments. We suggest that these mutations result in an instability in the transmission of determined states. PMID:6404678

  16. 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.

  17. 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

  18. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa.

    PubMed

    Jonkman, Marcel F; Pasmooij, Anna M G; Pasmans, Suzanne G M A; van den Berg, Maarten P; Ter Horst, Henk J; Timmer, Albertus; Pas, Hendri H

    2005-10-01

    The cytoplasmic plaque protein desmoplakin (DP), which is located in desmosomes, plays a major role in epithelial and muscle cell adhesion by linking the transmembrane cadherins to the cytoplasmic intermediate filament network. Mutations of DP may cause striate palmoplantar keratoderma, arrhythmogenic right ventricular dysplasia, skin fragility/woolly hair syndrome, Naxos-like disease, and Carvajal syndrome. DP must be indispensable, because DP-/- mice are early abortive. Here, we report a patient with severe fragility of skin and mucous membranes caused by genetic truncation of the DP tail. The new phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. The phenotype also comprised universal alopecia, neonatal teeth, and nail loss. Histology showed suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. Electron microscopy revealed disconnection of keratin intermediate filaments from desmosomes. Immunofluorescence staining of DP showed a distinct punctate intercellular pattern in the patient's skin. Protein analysis revealed expression of truncated DP polypeptides. Mutational analysis of the patient demonstrated compound heterozygosity for two DP mutations, 6079C-->T (R1934X) and 6370delTT, respectively. Aberrant mRNA transcripts that predict premature termination of translation with loss of the three intermediate filament-binding subdomains in the DP tail were detected by RT-PCR. The new dramatic phenotype, which we named "lethal acantholytic epidermolysis bullosa," underscores the paramount role of DP in epidermal integrity. PMID:16175511

  19. Serum amyloid A protects murine macrophages from lethal toxin-mediated death.

    PubMed

    Rose, Kira; Long, Paul; Shankar, Malini; Ballard, Jimmy D; Webb, Carol F

    2012-01-01

    Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to lethal toxin treatment. Moreover, pre-treatment of macrophages with exogenous SAA protected macrophages from lethal toxin-mediated death. Exogenous SAA activated the p38 mitogen activated protein kinase (MAP) kinase pathway, while lethal toxin mutants incapable of p38 activation were incapable of causing cell death. Chemical inhibition of the p38 activation pathway abrogated the protective effects of SAA. These data show that SAA affords protection against lethal toxin in mouse macrophages and link this response to the p38 pathway. PMID:22082566

  20. 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.

  1. The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA.

    PubMed Central

    Gebauer, F; Merendino, L; Hentze, M W; Valcárcel, J

    1998-01-01

    Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm. PMID:9570314

  2. 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

  3. 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

  4. 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

  5. Synthetic lethality-based targets for discovery of new cancer therapeutics.

    PubMed

    Weidle, Ulrich H; Maisel, Daniela; Eick, Dirk

    2011-01-01

    Synthetic lethality is based on the incompatibility of cell survival with the loss of function of two or more genes, not with loss of function of a single gene. If targets of synthetic lethality are deregulated or mutated in cancer cells, the strategy of synthetic lethality can result in significant increase of therapeutic efficacy and a favourable therapeutic window. In this review, we discuss synthetic lethality based on deficient DNA repair mechanisms, activating mutations of RAS, loss of function mutations of the tumor suppressor genes p53, Rb and von Hippel-Lindau, and disruption of interactive protein kinase networks in the context of development of new anticancer agents. PMID:21737609

  6. 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. PMID:22981215

  7. 77 FR 6548 - Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... Laboratory's (ARL's), Survivability, Lethality Analysis Directorate (SLAD) is a leader in ballistic..., telephone (410) 278- 5028. For further technical information, please contact Denise Jordan, (410)...

  8. The role of sub-lethal weapons in human rights abuse.

    PubMed

    Wright, S

    2001-01-01

    This article is based on two recent reports contracted by the European Parliament (EP), which assessed sub-lethal weapons as flexible tools of political control. It analyses the role and function of existing weapons systems in human rights abuses using examples from Indonesia, Israel, Kenya, Northern Ireland and Turkey. These weapons are designed to 'appear' rather than 'be' safe and, since they augment rather than replace lethal technologies, their use can distort conflicts and actually bridge the firewall between use of less-lethal and lethal technologies. PMID:11578040

  9. Animal vs. non-animal tests for the monitoring of marine biotoxins in the EU.

    PubMed

    Sauer, Ursula G

    2005-01-01

    Since bivalve molluscs can contain algae biotoxins that can cause gastroenterological or even lethal neurological diseases in humans, a public health control system on marine biotoxins has been implemented in EU Directive 91/492. Currently, the reference method laid down for this purpose is the so-called "mouse bioassay" with death of the animals as an endpoint. To date, this extremely distressful animal test has not been standardised or validated, and there is scientific evidence that it is neither relevant nor reliable. Therefore different EU Member States have been striving to replace the mouse bioassay or to reduce the animal numbers and the distress for the animals. In the United Kingdom, the test is being performed with two instead of three mice, the animals are anaesthetised before injection of the mollusc extract and remain in narcosis until their death. In Germany the mouse bioassay has not been performed for many years; without restriction of consumer health safety, marine biotoxins are detected with chemical analytical test methods. The application of alternative test methods is legally required according to EU Directive 86/609 on the Protection of Laboratory Animals. Apparently there is a conflict between two equal valid EU Directives, which has to be overcome. PMID:15719147

  10. 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.

  11. 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. PMID:24785379

  12. Transposon insertions causing constitutive sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing

    SciTech Connect

    Berstein, M.; Cline, T.W. |; Lersch, R.A.; Subrahmanyan, L.

    1995-02-01

    Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle {open_quotes}on{close_quotes} vs. {open_quotes}off{close_quotes} reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. {open_quotes}Male-lethal{close_quotes} (Sxl{sup M}) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, Sxl{sup M} haplo-X animals (chromosomal males) die because of improper dosage compensation, and Sxl{sup m} chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Transcript analysis of double-mutant male-viable Sxl{sup M} derivatives in which the Sxl{sup M} insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these Sxl{sup M} alleles is a consequence of an alteration of the structure of the pre-mRNA that allow some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of Sxl{sup M} alleles appears to depend on the mutant alleles` responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce. 47 refs., 10 figs., 4 tabs.

  13. Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor.

    PubMed

    Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2015-08-01

    Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. PMID:26145887

  14. 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

  15. 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

  16. The Aspartate-Semialdehyde Dehydrogenase of Edwardsiella ictaluri and Its Use as Balanced-Lethal System in Fish Vaccinology

    PubMed Central

    Santander, Javier; Xin, Wei; Yang, Zhao; Curtiss, Roy

    2010-01-01

    asdA mutants of Gram-negative bacteria have an obligate requirement for diaminopimelic acid (DAP), which is an essential constituent of the peptidoglycan layer of the cell wall of these organisms. In environments deprived of DAP, i.e., animal tissues, they will undergo lysis. Deletion of the asdA gene has previously been exploited to develop antibiotic-sensitive strains of live attenuated recombinant bacterial vaccines. Introduction of an Asd+ plasmid into a ΔasdA mutant makes the bacterial strain plasmid-dependent. This dependence on the Asd+ plasmid vector creates a balanced-lethal complementation between the bacterial strain and the recombinant plasmid. E. ictaluri is an enteric Gram-negative fish pathogen that causes enteric septicemia in catfish. Because E. ictaluri is a nasal/oral invasive intracellular pathogen, this bacterium is a candidate to develop a bath/oral live recombinant attenuated Edwardsiella vaccine (RAEV) for the catfish aquaculture industry. As a first step to develop an antibiotic-sensitive RAEV strain, we characterized and deleted the E. ictaluri asdA gene. E. ictaluri ΔasdA01 mutants exhibit an absolute requirement for DAP to grow. The asdA gene of E. ictaluri was complemented by the asdA gene from Salmonella. Several Asd+ expression vectors with different origins of replication were transformed into E. ictaluri ΔasdA01. Asd+ vectors were compatible with the pEI1 and pEI2 E. ictaluri native plasmids. The balanced-lethal system was satisfactorily evaluated in vivo. Recombinant GFP, PspA, and LcrV proteins were synthesized by E. ictaluri ΔasdA01 harboring Asd+ plasmids. Here we constructed a balanced-lethal system, which is the first step to develop an antibiotic-sensitive RAEV for the aquaculture industry. PMID:21209920

  17. Animal rights, animal minds, and human mindreading

    PubMed Central

    Mameli, M; Bortolotti, L

    2006-01-01

    Do non‐human animals have rights? The answer to this question depends on whether animals have morally relevant mental properties. Mindreading is the human activity of ascribing mental states to other organisms. Current knowledge about the evolution and cognitive structure of mindreading indicates that human ascriptions of mental states to non‐human animals are very inaccurate. The accuracy of human mindreading can be improved with the help of scientific studies of animal minds. However, the scientific studies do not by themselves solve the problem of how to map psychological similarities (and differences) between humans and animals onto a distinction between morally relevant and morally irrelevant mental properties. The current limitations of human mindreading—whether scientifically aided or not—have practical consequences for the rational justification of claims about which rights (if any) non‐human animals should be accorded. PMID:16446412

  18. Ear tuftedness: a lethal condition in the Araucana fowl.

    PubMed

    Somes, R G; Pabilonia, M S

    1981-01-01

    The lethal effects of the ear-tuft trait of the Araucana chicken are reported and the genetic basis of its inheritance is verified. The ear-tuft (Et) gene acts as an autosomal dominant with reduced penetrance in heterozygotes. This study gave two estimates of reduced penetrance, 4 and 14 percent. Homozygotes die during 17-19 days of incubation, although a few may hatch. Most of these die within a week, but occasionally an "escaper" will live to maturity; one such Et/Et individual was verified. Heterozygotes also experience increased embryonic mortality at about 20 or 21 days of incubation. In this study the average embryonic mortality among heterozygotes was 41.6 percent. Posthatch mortality also was significantly greater among tufted chicks than among nontufted chicks. PMID:7276512

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Clinical effects and lethal and forensic aspects of propofol.

    PubMed

    Levy, Richard J

    2011-01-01

    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 postmortem 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

  4. 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

  5. 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.

  6. Comparative study of the lethal effects of near-UV light (360 nm) and 8-methoxypsoralen plus near-UV on plasmid DNA

    SciTech Connect

    Paramio, J.M.; Bauluz, C.; de Vidania, R. )

    1991-01-01

    The authors have studied the lethality produced on pBR322 by near-UV radiation and by 8-Methoxypsoralen plus near-UV (PUV treatment). Samples of pBR322 DNA were irradiated with increasing fluences of 360 nm-light either in the absence or presence of 400 molecules of 8-Methoxypsoralen (8-MOP) per plasmid molecule. They have estimated to what extent the global lethality of PUVA treatment is due to the presence of psoralen adducts in DNA or to radiation itself. In order to analyse the involvement of DNA repair mechanisms in the removal of plasmid lesions, several strains of E. coli (differing in their repair capacities) they are used as recipients of the treated plasmids. Results showed that excision and recombination participate in the repair of near-UV-induced plasmid lesions. Repair of PUV-induced lesions showed an even greater requirement of the excision pathway. Besides, a slight increase on plasmid mutation frequencies was observed after near-UV or PUV treatment in wild type and uvrA cells. Estimation of the contribution of 8-MOP to the global lethality of PUV treatment showed that only the excision pathway was involved in removing psoralen adducts from plasmid DNA, suggesting the involvement of the recombinational pathway in the repair of near-UV-derived lesions.

  7. 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

  8. Henipavirus infections: lessons from animal models.

    PubMed

    Dhondt, Kévin P; Horvat, Branka

    2013-01-01

    The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed. PMID:25437037

  9. 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

  10. Bacillus anthracis Edema Toxin Causes Extensive Tissue Lesions and Rapid Lethality in Mice

    PubMed Central

    Firoved, Aaron M.; Miller, Georgina F.; Moayeri, Mahtab; Kakkar, Rahul; Shen, Yuequan; Wiggins, Jason F.; McNally, Elizabeth M.; Tang, Wei-Jen; Leppla, Stephen H.

    2005-01-01

    Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death in BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, lethal toxin. Observations of gross pathology showed intestinal intralumenal fluid accumulation followed by focal hemorrhaging of the ileum and adrenal glands. Histopathological analyses of timed tissue harvests revealed lesions in several tissues including adrenal glands, lymphoid organs, bone, bone marrow, gastrointestinal mucosa, heart, and kidneys. Concomitant blood chemistry analyses supported the induction of tissue damage. Several cytokines increased after ET administration, including granulocyte colony-stimulating factor, eotaxin, keratinocyte-derived cytokine, MCP-1/JE, interleukin-6, interleukin-10, and interleukin-1β. Physiological measurements also revealed a concurrent hypotension and bradycardia. These studies detail the extensive pathological lesions caused by ET and suggest that it causes death due to multiorgan failure. PMID:16251415

  11. Inflammatory Biomarkers Associated with Lethal Rift Valley Fever Encephalitis in the Lewis Rat Model

    PubMed Central

    Caroline, Amy L.; Kujawa, Michael R.; Oury, Tim D.; Reed, Douglas S.; Hartman, Amy L.

    2016-01-01

    Rift Valley fever (RVF) is an emerging viral disease that causes significant human and veterinary illness in Africa and the Arabian Peninsula. Encephalitis is one of the severe complications arising from RVF virus (RVFV) infection of people, and the pathogenesis of this form of RVF is completely unknown. We use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection. Lewis rats were infected with RVFV strain ZH501 by aerosol exposure, then sacrificed daily to determine the course of infection and evaluation of clinical, virological, and immunological parameters. Weight loss, fever, and clinical signs occurred during the last 1–2 days prior to death. Prior to onset of clinical indications of disease, rats displayed marked granulocytosis and thrombocytopenia. In addition, high levels of inflammatory chemokines (MCP-1, MCS-F, Gro/KC, RANTES, and IL-1β) were detected first in serum (3–5 dpi) followed by brain (5–7 dpi). The results of this study are consistent with clinical data from human RVF patients and validate Lewis rats as an appropriate small animal model for RVF encephalitis. The biomarkers we identified here will be useful in future studies evaluating the efficacy of novel vaccines and therapeutics. PMID:26779164

  12. Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies.

    PubMed

    Wachowicz, Paulina; Fernández-Miranda, Gonzalo; Marugán, Carlos; Escobar, Beatriz; de Cárcer, Guillermo

    2016-07-01

    Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays multiple and essential roles during the cell division cycle. Its inhibition in cultured cells leads to severe mitotic aberrancies and cell death. Whereas previous reports suggested that Plk1 depletion in mice leads to a non-mitotic arrest in early embryos, we show here that the bi-allelic Plk1 depletion in mice certainly results in embryonic lethality due to extensive mitotic aberrations at the morula stage, including multi- and mono-polar spindles, impaired chromosome segregation and cytokinesis failure. In addition, the conditional depletion of Plk1 during mid-gestation leads also to severe mitotic aberrancies. Our data also confirms that Plk1 is completely dispensable for mitotic entry in vivo. On the other hand, Plk1 haploinsufficient mice are viable, and Plk1-heterozygous fibroblasts do not harbor any cell cycle alterations. Plk1 is overexpressed in many human tumors, suggesting a therapeutic benefit of inhibiting Plk1, and specific small-molecule inhibitors for this kinase are now being evaluated in clinical trials. Therefore, the different Plk1 mouse models here presented are a valuable tool to reexamine the relevance of the mitotic kinase Plk1 during mammalian development and animal physiology. PMID:27417127

  13. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    PubMed Central

    Devera, T. Scott; Prusator, Dawn K.; Joshi, Sunil K.; Ballard, Jimmy D.; Lang, Mark L.

    2015-01-01

    Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities. PMID:26120785

  14. [Congenital and lethal semi-hairlessness in an Angler-Holstein crossbred calf].

    PubMed

    Reinartz, Sina; Schwittlick, Ulrike; Seehusen, Frauke; Distl, Ottmar

    2016-01-01

    A male Angler-Red Holstein crossbred calf was almost completely hairless since its birth. Hair growth was not observed within the course of its life, but with increasing age the hair structure changed from a thin and soft hair to a wiry to coarse hair fibre. Growth rate of the animal was reduced, body condition was poor but appetite was good. In addition, accompanying malformations were found including brachygnathia superior and a reduction or a particularly pronounced fine countenance skull ("shrew head"). The calf died unexpectedly at the age of five months. In the subsequent gross pathological and histopathological examination, a pronounced hyperkeratosis, degeneration of follicular epithelial cells, a reduced number of hair follicles, an increased number of telogen hair follicles, sclerosis of the corium, dilated apocrine glands and inflammatory changes of the gastrointestinal tract were seen. Based on the course of the disease, the phenotypic appearance of hypotrichosis and hair fibre as well as the histopathological changes the present case resembles a lethal semi-hairless form of hypotrichosis. This congenital anomaly in the present case is likely genetically determined. PMID:27169157

  15. Subcutaneous immunization with recombinant adenovirus expressing influenza A nucleoprotein protects mice against lethal viral challenge.

    PubMed

    Hashem, Anwar; Jaentschke, Bozena; Gravel, Caroline; Tocchi, Monika; Doyle, Tracey; Rosu-Myles, Michael; He, Runtao; Li, Xuguang

    2012-04-01

    Current influenza vaccines mainly induce strain-specific neutralizing antibodies and need to be updated each year, resulting in significant burdens on vaccine manufacturers and regulatory agencies. Genetic immunization strategies based on the highly conserved nucleoprotein (NP) of influenza have attracted great attention as NP could induce heterosubtypic immunity. It is unclear, however, whether different forms of vectors and/or vaccination regimens could have contributed to the previously reported discrepancies in the magnitude of protection of NP-based genetic vaccinations. Here, we evaluated a plasmid DNA vector (pNP) and a recombinant adenovirus vector (rAd-NP) containing the NP gene through various combinations of immunization regimens in mice. We found that pNP afforded only partial protection even after 4 injections, with full protection against lethal challenge achieved only with the fourth boost using rAd-NP. Alternatively, only two doses of rAd-NP delivered subcutaneously were needed to induce an enhanced immune response and completely protect the animals, a finding which, to our knowledge, has not been reported before. PMID:22370512

  16. Hypothyroidism renders protection against lethal ventricular arrhythmias in a conscious canine model of sudden death.

    PubMed

    Venkatesh, N; Lynch, J J; Uprichard, A C; Kitzen, J M; Singh, B N; Lucchesi, B R

    1991-11-01

    The protective effect of hypothyroidism against lethal ventricular tachyarrhythmias (VT) in the subacute phase of experimental myocardial infarction (MI) was investigated in 10 thyroidectomized dogs using a conscious model of sudden coronary death. Four weeks after surgical ablation of the thyroid, and having established biochemical hypothyroidism, anterior MI was produced by 120 min of occlusion-reperfusion of the left anterior descending coronary artery. In the subacute phase of MI, the inducibility of VT was investigated using programmed ventricular stimulation (PVS), and the effects on spontaneous development of ventricular fibrillation (VF) were studied by production of posterolateral ischemia at a site remote from the area of the previous infarction. Ischemia was produced by the passage of anodal direct current through a silver wire electrode implanted in the left circumflex coronary (LCX) artery. The results were compared to those from a cohort of 20 existing euthyroid controls that had undergone an identical experimental protocol. No differences were found in heart rate and other electrocardiographic parameters such as the PR, QRS, and QT (paced at 2.5 Hz) and the QTc interval between the hypo- and euthyroid groups. During PVS in the subacute phase of anterior MI, the measured threshold voltage and ventricular refractory periods were similar in both groups. The incidence of inducibility of VT was 100% in the euthyroid animals compared to 60% in the hypothyroid dogs, suggesting an antiarrhythmic effect of hypothyroidism. The incidence of sustained vs. nonsustained VT was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1723767

  17. Gene Rearrangement Attenuates Expression and Lethality of a Nonsegmented Negative Strand RNA Virus

    NASA Astrophysics Data System (ADS)

    Williams Wertz, Gail; Perepelitsa, Victoria P.; Ball, L. Andrew

    1998-03-01

    The nonsegmented negative strand RNA viruses comprise hundreds of human, animal, insect, and plant pathogens. Gene expression of these viruses is controlled by the highly conserved order of genes relative to the single transcriptional promoter. We utilized this regulatory mechanism to alter gene expression levels of vesicular stomatitis virus by rearranging the gene order. This report documents that gene expression levels and the viral phenotype can be manipulated in a predictable manner. Translocation of the promoter-proximal nucleocapsid protein gene N, whose product is required stoichiometrically for genome replication, to successive positions down the genome reduced N mRNA and protein expression in a stepwise manner. The reduction in N gene expression resulted in a stepwise decrease in genomic RNA replication. Translocation of the N gene also attenuated the viruses to increasing extents for replication in cultured cells and for lethality in mice, without compromising their ability to elicit protective immunity. Because monopartite negative strand RNA viruses have not been reported to undergo homologous recombination, gene rearrangement should be irreversible and may provide a rational strategy for developing stably attenuated live vaccines against this type of virus.

  18. 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.

  19. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge.

    PubMed

    Devera, T Scott; Prusator, Dawn K; Joshi, Sunil K; Ballard, Jimmy D; Lang, Mark L

    2015-07-01

    Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities. PMID:26120785

  20. Physics for Animation Artists

    ERIC Educational Resources Information Center

    Chai, David; Garcia, Alejandro L.

    2011-01-01

    Animation has become enormously popular in feature films, television, and video games. Art departments and film schools at universities as well as animation programs at high schools have expanded in recent years to meet the growing demands for animation artists. Professional animators identify the technological facet as the most rapidly advancing…

  1. Evaluating the Progenitor Cells of Ovarian Cancer: Analysis of Current Animal Models

    PubMed Central

    King, Shelby M.; Burdette, Joanna E.

    2013-01-01

    Serous ovarian cancer is one of the most lethal gynecological malignancies. Progress on effective diagnostics and therapeutics for this disease are hampered by ambiguity as to the cellular origins of this histotype of ovarian cancer, as well as limited suitable animal models to analyze early stages of disease. In this report, we will review current animal models with respect to the two proposed progenitor cells for serous ovarian cancer, the ovarian surface epithelium and the fallopian tube epithelium. PMID:21777513

  2. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques

    PubMed Central

    Warren, Travis K.; Whitehouse, Chris A.; Wells, Jay; Welch, Lisa; Charleston, Jay S.; Heald, Alison; Nichols, Donald K.; Mattix, Marc E.; Palacios, Gustavo; Kugleman, Jeffrey R.; Iversen, Patrick L.; Bavari, Sina

    2016-01-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83–100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI. PMID:26901785

  3. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    PubMed

    Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

    2016-02-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI. PMID:26901785

  4. Choice of inbred rat strain impacts lethality and disease course after respiratory infection with Rift Valley Fever Virus

    PubMed Central

    Bales, Jacquelyn M.; Powell, Diana S.; Bethel, Laura M.; Reed, Douglas S.; Hartman, Amy L.

    2012-01-01

    Humans infected with Rift Valley Fever Virus (RVFV) generally recover after a febrile illness; however, a proportion of patients progress to a more severe clinical outcome such as hemorrhagic fever or meningoencephalitis. RVFV is naturally transmitted to livestock and humans by mosquito bites, but it is also infectious through inhalational exposure, making it a potential bioterror weapon. To better understand the disease caused by inhalation of RVFV, Wistar-Furth, ACI, or Lewis rats were exposed to experimental aerosols containing virulent RVFV. Wistar-Furth rats developed a rapidly progressing lethal hepatic disease after inhalational exposure; ACI rats were 100-fold less susceptible and developed fatal encephalitis after infection. Lewis rats, which do not succumb to parenteral inoculation with RVFV, developed fatal encephalitis after aerosol infection. RVFV was found in the liver, lung, spleen, heart, kidney and brain of Wistar Furth rats that succumbed after aerosol exposure. In contrast, RVFV was found only in the brains of ACI or Lewis rats that succumbed after aerosol exposure. Lewis rats that survived s.c. infection were not protected against subsequent re-challenge by aerosol exposure to the homologous virus. This is the first side-by-side comparison of the lethality and pathogenesis of RVFV in three rat strains after aerosol exposure and the first step toward developing a rodent model suitable for use under the FDA Animal Rule to test potential vaccines and therapeutics for aerosol exposure to RVFV. PMID:22919694

  5. Comparison of less lethal 40 mm sponge projectile and the 37 mm projectile for injury assessment on human thorax

    NASA Astrophysics Data System (ADS)

    Nsiampa, N.; Robbe, C.; Oukara, A.; Papy, A.

    2012-08-01

    Since there is an increasing interest in avoiding human body injury in diverse situations like crowd control or peacekeeping missions, less lethal ammunition are more and more used. In this study we focus only on kinetic energy non-lethal (KENLW) projectiles. Their desired effects on human body are the temporary incapacitation through blunt trauma. There are different types of KENLW projectiles ranging from rigid to deformable projectiles. Unfortunately, the effects of such projectiles are not really well known as it is difficult to measure the force transmitted to the human body or the related deformation. Because the potential of injury excludes human living tests, tests are performed on cadavers, animals or human tissue surrogates. Besides these tests, numerical simulations are more and more used to gain more understanding, to assess or to predict the effects of this kind of projectile on human body. In this paper a comparison based on the viscous criterion between the 37 mm rigid projectile and the 40 mm sponge projectile was made.

  6. Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R.

    PubMed

    Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-03-01

    Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2-) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R. PMID:26927174

  7. Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R

    PubMed Central

    Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-01-01

    Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2−) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R. PMID:26927174

  8. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus▿

    PubMed Central

    McCray, Paul B.; Pewe, Lecia; Wohlford-Lenane, Christine; Hickey, Melissa; Manzel, Lori; Shi, Lei; Netland, Jason; Jia, Hong Peng; Halabi, Carmen; Sigmund, Curt D.; Meyerholz, David K.; Kirby, Patricia; Look, Dwight C.; Perlman, Stanley

    2007-01-01

    The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies. PMID:17079315

  9. 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.

  10. Early and late B cell immune responses in lethal and self-cured rodent malaria.

    PubMed

    Azcárate, Isabel G; Marín-García, Patricia; Pérez-Benavente, Susana; Diez, Amalia; Puyet, Antonio; Bautista, José M

    2015-05-01

    ICR mice have heterogeneous susceptibility to lethal Plasmodium yoelii yoelii 17XL from the first days of experimental infection as evidenced by the different parasitemia levels and clinical outcomes. This mouse model has revealed specific immune responses on peripheral blood correlating with the infection fate of the animals. To search for immune-markers linked to parasitemia we examined B lymphocytes in organs of the immune system as key effectors of rodent immunity against malaria. To determine changes in immune cellularity fostered by the different prognostic parasitemia we examined B cell subsets in low (<15%) and high (>50%) parasitized mice during the first days of the infection. In the case of surviving mice, we studied the preservation of memory immune response 500 days after the primary P. yoelii challenge. Correlating with the parasitemia level, it was observed an increase in total cellularity of spleen during the first week of infection which remained after 16 months of the infection in surviving animals. B cell subsets were also modified across the different infection fates. Subpopulation as follicular B cells and B-1 cells proportions behaved differently depending on the parasitemia kinetics. In addition, peritoneal cavity cells proliferated in response to high parasitemia. More significantly, P. yoelii -specific memory B cells remained in the spleen 500 days after the primo-infection. This study demonstrates that B cell kinetics is influenced by the different parasitemia courses which are naturally developed within a same strain of untreated mice. We show that high levels of parasitemia at the beginning of infection promote an extremely fast and exacerbate response of several cell populations in spleen and peritoneal cavity that, in addition, do not follow the kinetics observed in peripheral blood. Furthermore, our results describe the longest persistence of memory B cells long time upon a single malaria infection in mice. PMID:25466589

  11. Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection

    PubMed Central

    Leite, Juliana A.; Bargieri, Daniel Y.; Carvalho, Bruna O.; Albrecht, Letusa; Lopes, Stefanie C. P.; Kayano, Ana Carolina A. V.; Farias, Alessandro S.; Chia, Wan Ni; Claser, Carla; Malleret, Benoit; Russell, Bruce; Castiñeiras, Catarina; Santos, Leonilda M. B.; Brocchi, Marcelo; Wunderlich, Gerhard; Soares, Irene S.; Rodrigues, Mauricio M.; Rénia, Laurent

    2015-01-01

    Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4+, but not CD8+, T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection. PMID:26169268

  12. A novel balanced-lethal host-vector system based on glmS.

    PubMed

    Kim, Kwangsoo; Jeong, Jae Ho; Lim, Daejin; Hong, Yeongjin; Yun, Misun; Min, Jung-Joon; Kwak, Sahng-June; Choy, Hyon E

    2013-01-01

    During the last decade, an increasing number of papers have described the use of various genera of bacteria, including E. coli and S. typhimurium, in the treatment of cancer. This is primarily due to the facts that not only are these bacteria capable of accumulating in the tumor mass, but they can also be engineered to deliver specific therapeutic proteins directly to the tumor site. However, a major obstacle exists in that bacteria because the plasmid carrying the therapeutic gene is not needed for bacterial survival, these plasmids are often lost from the bacteria. Here, we report the development of a balanced-lethal host-vector system based on deletion of the glmS gene in E. coli and S. typhimurium. This system takes advantage of the phenotype of the GlmS(-) mutant, which undergoes lysis in animal systems that lack the nutrients required for proliferation of the mutant bacteria, D-glucosamine (GlcN) or N-acetyl-D-glucosamine (GlcNAc), components necessary for peptidoglycan synthesis. We demonstrate that plasmids carrying a glmS gene (GlmS(+)p) complemented the phenotype of the GlmS(-) mutant, and that GlmS(+) p was maintained faithfully both in vitro and in an animal system in the absence of selection pressure. This was further verified by bioluminescent signals from GlmS (+)pLux carried in bacteria that accumulated in grafted tumor tissue in a mouse model. The signal was up to several hundred-fold stronger than that from the control plasmid, pLux, due to faithful maintenance of the plasmid. We believe this system will allow to package a therapeutic gene onto an expression plasmid for bacterial delivery to the tumor site without subsequent loss of plasmid expression as well as to quantify bioluminescent bacteria using in vivo imaging by providing a direct correlation between photon flux and bacterial number. PMID:23555984

  13. Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection.

    PubMed

    Leite, Juliana A; Bargieri, Daniel Y; Carvalho, Bruna O; Albrecht, Letusa; Lopes, Stefanie C P; Kayano, Ana Carolina A V; Farias, Alessandro S; Chia, Wan Ni; Claser, Carla; Malleret, Benoit; Russell, Bruce; Castiñeiras, Catarina; Santos, Leonilda M B; Brocchi, Marcelo; Wunderlich, Gerhard; Soares, Irene S; Rodrigues, Mauricio M; Rénia, Laurent; Costa, Fabio T M

    2015-10-01

    Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4(+), but not CD8(+), T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection. PMID:26169268

  14. Animals in space

    NASA Technical Reports Server (NTRS)

    White, Angela

    1988-01-01

    Animals are indispensable to the space program. Their continued use could have many significant results. Those who are opposed to using animals in space should remember that space animals are treated humanely; they are necessary because results can be obtained from them that would be unobtainable from humans; and results from animal experiments can be applied to human systems. Therefore, NASA should continue to use animals in space research.

  15. Animal issues and society.

    PubMed

    Grabau, J H

    1993-05-01

    Animal use topics are sensitive issues today. Animal uses issues are often presented as black and white or 'we' are right and 'they' are wrong. This is clearly demonstrated in the available literature from most organizations. Topics presented will include: delineation of issues and concerned groups; examples of animal issues in education and agriculture; the terrorist issue; examples of animal issues/sportsman issues; examples of political and legislative impact; and examples of biomedical and toxicology animal use issues. PMID:8516774

  16. 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.

  17. 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

  18. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reporting recommendations as specified under 40 CFR part 792, subpart J the following specific information... and 50 pregnant females per mating interval. (iv) Assignment to groups. Animals shall be...

  19. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... reporting recommendations as specified under 40 CFR part 792, subpart J the following specific information... and 50 pregnant females per mating interval. (iv) Assignment to groups. Animals shall be...

  20. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... reporting recommendations as specified under 40 CFR part 792, subpart J the following specific information... and 50 pregnant females per mating interval. (iv) Assignment to groups. Animals shall be...

  1. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... reporting recommendations as specified under 40 CFR part 792, subpart J the following specific information... and 50 pregnant females per mating interval. (iv) Assignment to groups. Animals shall be...

  2. 40 CFR 798.5450 - Rodent dominant lethal assay.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reporting recommendations as specified under 40 CFR part 792, subpart J the following specific information... and 50 pregnant females per mating interval. (iv) Assignment to groups. Animals shall be...

  3. The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats.

    PubMed Central

    Mancilla, J; García, P; Dinarello, C A

    1993-01-01

    Klebsiella pneumoniae, a worldwide cause of nosocomial infections, is one of the most common causes of death in newborns in nurseries. In this study, we investigated the role of interleukin-1 (IL-1) in an experimental animal model of neonatal sepsis, using a natural antagonist of IL-1 receptors, the IL-1 receptor antagonist (IL-1Ra), to block IL-1's effects in neonatal Klebsiella sepsis in the absence of antibiotic treatment. Newborn Wistar-Kyoto rats were injected intraperitoneally with a single dose (10 mg/kg) of either IL-1Ra (n = 43) or human serum albumin as a control (n = 40). At the same time, a 50% lethal dose of K. pneumoniae was injected subcutaneously. No antibiotics were given at any time. After 10 days, survival was 60% for the albumin group and 80% for the IL-1Ra group (P < 0.01). IL-1Ra treatment also afforded protection when the dose of bacteria was increased sixfold (P < 0.01). There were two episodes of leukopenia in the control group, which were suppressed by IL-1Ra (P < 0.01 and P < 0.001). IL-1 and IL-6 levels were lower in the IL-1Ra-treated group (P < 0.05 and P < 0.001, respectively). No differences between the two groups were observed in the number of bacteria in cultures of the blood, lungs, liver, or spleen. When IL-1Ra (10 mg/kg) was given both at time zero and 24 h after bacterial challenge, lethality was significantly increased (P < 0.01). Single doses of IL-1Ra of from 20 to 40 mg/kg progressively increased lethality compared with controls (P < 0.01) in both Wistar-Kyoto and Sprague-Dawley strain rats. In the same model, low doses of IL-1 itself (0.4 ng per rat), given 24 h prior to bacterial challenge, afforded protection (P < 0.001). These studies suggest that, in the absence of antibiotics, partial blockade of IL-1 receptors improves survival, whereas a longer or greater blockade increases lethality in newborn rats infected with K. pneumoniae. PMID:8432613

  4. Effects of Training with Lethal Chemicals on Job Proficiency and Job Confidence.

    ERIC Educational Resources Information Center

    Smith, Paula; And Others

    A study was designed to determine if soldiers trained to use chemical agents are more proficient in performing their jobs in an environment where lethal chemical agents are used and more confident of their ability to survive. A treatment group, composed of 150 soldiers, knew that their training would involve lethal agents in the Chemical…

  5. The Danger Assessment: Validation of a Lethality Risk Assessment Instrument for Intimate Partner Femicide

    ERIC Educational Resources Information Center

    Campbell, Jacquelyn C.; Webster, Daniel W.; Glass, Nancy

    2009-01-01

    The Danger Assessment (DA) is an instrument designed to assess the likelihood of lethality or near lethality occurring in a case of intimate partner violence. This article describes the development, psychometric validation, and suggestions for use of the DA. An 11-city study of intimate partner femicide used multivariate analysis to test the…

  6. Evaluating the Predictive Validity of Suicidal Intent and Medical Lethality in Youth

    ERIC Educational Resources Information Center

    Sapyta, Jeffrey; Goldston, David B.; Erkanli, Alaattin; Daniel, Stephanie S.; Heilbron, Nicole; Mayfield, Andrew; Treadway, S. Lyn

    2012-01-01

    Objectives: To examine whether suicidal intent and medical lethality of past suicide attempts are predictive of future attempts, the association between intent and lethality, and the consistency of these characteristics across repeated attempts among youth. Method: Suicide attempts in a 15-year prospective study of 180 formerly psychiatrically…

  7. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including chemical agents. 552.25 Section 552.25 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF... 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...

  8. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., including chemical agents. 552.25 Section 552.25 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF... 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...

  9. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including chemical agents. 552.25 Section 552.25 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF... 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...

  10. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., including chemical agents. 552.25 Section 552.25 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF... 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...

  11. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information shall be reported... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Sex-linked recessive lethal test in....5275 Sex-linked recessive lethal test in drosophila melanogaster. (a) Purpose. The sex-linked...

  12. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information shall be reported... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Sex-linked recessive lethal test in....5275 Sex-linked recessive lethal test in drosophila melanogaster. (a) Purpose. The sex-linked...

  13. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information shall be reported... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Sex-linked recessive lethal test in....5275 Sex-linked recessive lethal test in drosophila melanogaster. (a) Purpose. The sex-linked...

  14. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information shall be reported... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Sex-linked recessive lethal test in....5275 Sex-linked recessive lethal test in drosophila melanogaster. (a) Purpose. The sex-linked...

  15. We want what’s best for our baby: Prenatal Parenting of Babies with Lethal Conditions

    PubMed Central

    Côté-Arsenault, Denise; Krowchuk, Heidi; Hall, Wendasha Jenkins; Denney-Koelsch, Erin

    2015-01-01

    This article reports on qualitative research into the experience of couples who chose to continue their pregnancies after receiving a lethal fetal diagnosis, and to embrace the parenting of their baby in the shortened time they have. This analysis of interview data is part of a larger research project describing parents’ experiences of continuing pregnancy with a known lethal fetal diagnosis (LFD). PMID:26594107

  16. BIOASSAY PROTOCOL FOR LETHAL AND SUBLETHAL EFFECTS OF FUNGAL PATHOGENS ON CHRYSOPERLA CARNEA

    EPA Science Inventory

    This practice describes procedures for evaluating the lethal and sub-lethal effects of exposure to fungal pathogens on larvae and adults of the predatory insect Chrysoperla carnea (Stephens). his practice was developed and tested with the fungal insect pathogen Beauveria bassiana...

  17. Examining the Impact of Psychiatric Diagnosis and Comorbidity on the Medical Lethality of Adolescent "Suicide Attempts"

    ERIC Educational Resources Information Center

    Mc Manama O'Brien, Kimberly H.; Berzin, Stephanie C.

    2012-01-01

    Specific psychiatric diagnoses and comorbidity patterns were examined to determine if they were related to the medical lethality of "suicide attempts" among adolescents presenting to an urban general hospital (N = 375). Bivariate analysis showed that attempters with substance abuse disorders had higher levels of lethality than attempters without…

  18. Co-lethality studied as an asset against viral drug escape: the HIV protease case

    PubMed Central

    2010-01-01

    Background Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. Results From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. Conclusions These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. Reviewers This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke. PMID:20565756

  19. Ethical language and decision-making for prenatally diagnosed lethal malformations.

    PubMed

    Wilkinson, Dominic; de Crespigny, Lachlan; Xafis, Vicki

    2014-10-01

    In clinical practice, and in the medical literature, severe congenital malformations such as trisomy 18, anencephaly, and renal agenesis are frequently referred to as 'lethal' or as 'incompatible with life'. However, there is no agreement about a definition of lethal malformations, nor which conditions should be included in this category. Review of outcomes for malformations commonly designated 'lethal' reveals that prolonged survival is possible, even if rare. This article analyses the concept of lethal malformations and compares it to the problematic concept of 'futility'. We recommend avoiding the term 'lethal' and suggest that counseling should focus on salient prognostic features instead. For conditions with a high chance of early death or profound impairment in survivors despite treatment, perinatal and neonatal palliative care would be ethical. However, active obstetric and neonatal management, if desired, may also sometimes be appropriate. PMID:25200733

  20. Effect of lethality on the extinction and on the error threshold of quasispecies.

    PubMed

    Tejero, Hector; Marín, Arturo; Montero, Francisco

    2010-02-21

    In this paper the effect of lethality on error threshold and extinction has been studied in a population of error-prone self-replicating molecules. For given lethality and a simple fitness landscape, three dynamic regimes can be obtained: quasispecies, error catastrophe, and extinction. Using a simple model in which molecules are classified as master, lethal and non-lethal mutants, it is possible to obtain the mutation rates of the transitions between the three regimes analytically. The numerical resolution of the extended model, in which molecules are classified depending on their Hamming distance to the master sequence, confirms the results obtained in the simple model and shows how an error catastrophe regime changes when lethality is taken in account. PMID:19833133