WorldWideScience

Sample records for mice survive longer

  1. Effect of bifidobacteria implantation on the survival time of whole-body irradiated mice

    International Nuclear Information System (INIS)

    Yokokura, Teruo; Onoue, Masaharu; Mutai, Masahiko

    1980-01-01

    Letahl dose (2 KR) of gamma-ray was irradiated on the whole bodies of mice. Survival time after irradiation was significantly longer in mice with administration of both Bifidobacterium breve YIT 4008 and transgalactosyl oligosaccharide than in mice with administration of either of the two or nothing. (Tsunoda, M.)

  2. Lower Bmi-1 Expression May Predict Longer Survival of Colon Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xiaodong Li

    2016-11-01

    Full Text Available Background: This study aimed to investigate the Bmi-1 expression and the clinical significance in colon cancer (CC. Patients and Methods: Bmi-1 expression in tumor tissue and the corresponding normal tissue was detected using immunohistological staining. The correlations between Bmi-1 expression and clinicopathological characteristics and the overall survival (OS time were analyzed. Results: The median H-scores of Bmi-1 in CC tissues and the corresponding tissues were 80.0 (0-270 and 5.0 (0-90, with no statistically significant difference (Z=-13.7, PP = 0.123. The survival rates of patients with low Bmi-1 expression were higher than those of patients with high Bmi-1 expression but the differences were not statistically significant. Conclusion: Bmi-1 expression in CC tissue is significantly higher than that in corresponding normal tissue. While there may be a trend towards improved survival, this is not statistically significant.

  3. Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Christensen, Karina; Offenberg, Hanne Kjær

    2009-01-01

    In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in glioma...

  4. Higher dietary lycopene intake is associated with longer cardiac event-free survival in patients with heart failure.

    Science.gov (United States)

    Biddle, Martha; Moser, Debra; Song, Eun Kyeung; Heo, Seongkum; Payne-Emerson, Heather; Dunbar, Sandra B; Pressler, Susan; Lennie, Terry

    2013-08-01

    The antioxidant lycopene may be beneficial for patients with heart failure (HF). Processed tomato products are a major source of lycopene, although they are also high in sodium. Increased sodium intake may counter the positive antioxidant effect of lycopene. This was a prospective study of 212 patients with HF. Dietary intake of lycopene and sodium was obtained from weighted 4-day food diaries. Patients were grouped by the median split of lycopene of 2471 µg/day and stratified by daily sodium levels above and below 3 g/day. Patients were followed for 1 year to collect survival and hospitalization data. Cox proportional hazards modeling was used to compare cardiac event-free survival between lycopene groups within each stratum of sodium intake. Higher lycopene intake was associated with longer cardiac event-free survival compared with lower lycopene intake (p = 0.003). The worst cardiac event-free survival was observed in the low lycopene intake group regardless of sodium intake (> 3 g/day HR = 3.01; p = 0.027 and ≤ 3 g/day HR= 3.34; p = 0.023). These findings suggest that increased lycopene intake has the potential to improve cardiac event-free survival in patients with HF independent of sodium intake.

  5. Slower Decline in C-Reactive Protein after an Inflammatory Insult Is Associated with Longer Survival in Older Hospitalised Patients.

    Directory of Open Access Journals (Sweden)

    Maryam Barma

    Full Text Available Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP, as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality.Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and to <50mg/L if peak values were greater than 50mg/L was derived from biochemistry data. 6-month survival plots were conducted on quartiles of CRP recovery indices. Cox proportional hazards models were used to test univariate and multivariate predictors of 6-month mortality. Covariates included age, sex, number of medications, serum calcium, haemoglobin level, renal function, and the presence of previous myocardial infarction, stroke, chronic heart failure, COPD and diabetes.3723 patients, mean age 84 years, were included. 1535 (41% were male and 733 (20% died during six-month follow-up. The lower an individual's peak CRP reading, and the longer the time taken for their CRP to fall, the better their 6-month survival. The time for CRP to reach half of its maximum value was the best dynamic CRP index of survival (HR 0.93 per week, 95% CI 0.89 to 0.98; p = 0.004; this remained significant even after adjustment for maximum CRP level and covariates listed above.CRP recovery indices are associated with survival in older people; further work is required to explain differences in physiology between patients with a fast and slow CRP recovery.

  6. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    Science.gov (United States)

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  7. Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.

    Science.gov (United States)

    Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

    2018-04-01

    Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients. This was a retrospective cohort study of adult patients with advanced nonthyroidal cancer treated with TKI and available thyroid function testing at three affiliated academic hospitals from 2000 to 2017. Patients with preexisting thyroid disease were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid status with TKI treatment was determined from thyroid function testing and initiation of thyroid medication, and classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement). Multivariate models were used to evaluate the effect of TKI-related hypothyroidism on overall survival (OS). Of 1120 initial patients, 538 remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%) patients with TKI therapy. Patients with hypothyroidism had significantly longer OS, with median OS in euthyroid patients of 685 days [confidence interval (CI) 523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991] in OH patients (p hypothyroid patients (SCH and OH) with TSH >5 and hypothyroidism in cancer patients treated with TKI is associated with significantly improved OS, should not necessitate TKI dose reduction or discontinuation, and may provide independent prognostic information.

  8. Effect of dendrobium candidum wall. exlindl drop on survival condition and spleen of mice with raddiation injury

    International Nuclear Information System (INIS)

    Qin Qiurong; Zhang Guoqing

    2010-01-01

    Objective: To study the effect of Dendrobium candidum Wall. exlindl drop(DCWD) on survival condition and pathological change of spleen of mice with radiation injury. Methods: One hundred and twenty-five BALB/c mice were divided into the control group, irradiation-injured group and DCWD groups which were divided into three groups according to the dose of DCWD. The survival condition of irradiated mice and its pathological change of spleen were observed. Results: The mean survival time of mice in each group irradiated with X-ray were shorter than that in the control group (P < 0.01), but in the DCWD groups survival is longer than that in the irradiation-injured group (P < 0.01). Acute radiation injury of spleen emerged. The pathological change degree was slight in the DCWD groups, and can recover quickly. But there was not conspicuous dose-effect relationship DCWD groups. Conclusion: DCWD can prolong the mean survival time,improve the survival rate of irradiated mice, and relieve the degree of pathological change in spleen of mice with radiation injury; DCWD has certain protective effect on radiation-injury. (authors)

  9. Tetranectin positive expression in tumour tissue leads to longer survival in Danish women with ovarian cancer. Results from the 'Malova' ovarian cancer study

    DEFF Research Database (Denmark)

    Heeran, Mel C; Rask, Lene; Høgdall, Claus K

    2015-01-01

    of the disease. Using tissue arrays we analysed the expression levels in tissues from 166 women with borderline ovarian tumours (BOTs) and 592 women with ovarian cancer (OC). A panel of three antibodies was used for immunohistochemistry: a polyclonal and two monoclonal antibodies. Serum TN was measured using...... found to imply longer OS (p Kaplan-Meier survival analysis performed on all OC cases showed a significantly longer OS (p = 0...

  10. Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock

    Directory of Open Access Journals (Sweden)

    Charchaflieh J

    2012-07-01

    observed in tg-TX mice. There was no difference in the survival time between tg-JAX and WT-JAX groups after endotoxic shock (P > 0.05. However, the survival time in the tg-TX group was more than twofold longer than that in the WT-TX group (P < 0.05. In addition, WT-JAX mice survived significantly longer than WT-TX mice (P < 0.05.Conclusion: Aberrant decrease of endogenous SOD1 activities may have overshadowed the effect of overexpression of SOD1 in tg mice (tg-JAX. Mice with C57BL/6J background (tg-TX are more susceptible to lipopolysaccharide-induced endotoxic shock than those with mixed genetic background (tg-JAX. Overexpression of SOD1 is protective only in mice with C57BL/6J background (tg-TX.Keywords: human SOD1 enzyme, endotoxic shock, transgenic mice, protective effect

  11. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    Science.gov (United States)

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  12. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

    Science.gov (United States)

    Fitzhugh, Courtney D; Hsieh, Matthew M; Allen, Darlene; Coles, Wynona A; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P; Rodgers, Griffin P; Schechter, Alan N; Tisdale, John F; Taylor, James G

    2015-01-01

    Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, phydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

  13. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

    Directory of Open Access Journals (Sweden)

    Courtney D Fitzhugh

    Full Text Available Adults with sickle cell anemia (HbSS are inconsistently treated with hydroxyurea.We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001, kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043, and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082. Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040. This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050. Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004. While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively, other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose

  14. Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice

    Directory of Open Access Journals (Sweden)

    Sytwu Huey-Kang

    2009-08-01

    Full Text Available Abstract Pancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD mice. Methods Islets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-TRX or enhanced green fluorescence protein (Lt-eGFP, respectively. Transduced islets were transplanted under the left kidney capsule of female diabetic NOD mice, and blood glucose concentration was monitored daily after transplantation. The histology of the islet graft was assessed at the end of the study. The protective effect of TRX on islets was investigated. Results The lentiviral vector effectively transduced islets without altering the glucose-stimulating insulin-secretory function of islets. Overexpression of TRX in islets reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRX-transduced islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs. 6.5 days (n = 9 and 10, respectively, p Conclusion We successfully transduced the TRX gene into islets and demonstrated that these genetically modified grafts are resistant to inflammatory insult and survived longer in diabetic recipients. Our results further support the concept that the reactive oxygen species (ROS scavenger and antiapoptotic functions of TRX are critical to islet survival after

  15. Suppressing an anti-inflammatory cytokine reveals a strong age-dependent survival cost in mice.

    Directory of Open Access Journals (Sweden)

    Virginia Belloni

    Full Text Available BACKGROUND: The central paradigm of ecological immunology postulates that selection acts on immunity as to minimize its cost/benefit ratio. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions. In addition to these resource-based costs, mis-directed or over-reacting immune responses can be particularly harmful for the host. In spite of the potential importance of immunopathology, most studies dealing with the evolution of the immune response have neglected such non resource-based costs. To keep the immune response under control, hosts have evolved regulatory pathways that should be considered when studying the target of the selection pressures acting on immunity. Indeed, variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences. METHODOLOGY/PRINCIPAL FINDINGS: Here, we experimentally assessed the survival costs of reduced immune regulation by inhibiting an anti-inflammatory cytokine (IL-10 with anti-IL-10 receptor antibodies (anti-IL-10R in mice that were either exposed to a mild inflammation or kept as control. The experiment was performed on young (3 months and old (15 months individuals, as to further assess the age-dependent cost of suppressing immune regulation. IL-10 inhibition induced high mortality in old mice exposed to the mild inflammatory insult, whereas no mortality was observed in young mice. However, young mice experienced a transitory lost in body mass when injected with the anti-IL-10R antibodies, showing that the treatment was to a lesser extent also costly for young individuals. CONCLUSIONS: These results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity.

  16. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  17. HLA-A, -B, and -DR zero-mismatched kidneys shipped to the University of Wisconsin, Madison, 1993-2006: superior graft survival despite longer preservation time.

    Science.gov (United States)

    Burlingham, William J; Muñoz del Rio, Alejandro; Lorentzen, David; Sollinger, Hans W; Pirsch, John D; Jankowska-Gan, Ewa; D'Alessandro, Anthony

    2010-08-15

    To determine the impact at a single center of the United Network for Organ Sharing-mandated sharing program for human leukocyte antigen (HLA)-A/-B/-DR 0-mismatched (0MM) kidneys, we analyzed the results of 264 kidney transplants from 0MM distant donors between 1993 and 2006, with a follow-up through January 31, 2007. We compared these results with that of concurrent kidneys transplanted from HLA more than 0MM local donors and with shipped more than 0MM kidneys from "payback" donors. Despite a significantly longer preservation time, we found an 11% increase in 8-year graft survival (63% vs. 52%; P0MM donor kidneys. Graft survival of 0MM shipped kidneys at 8 years was significantly better in nonsensitized (or=20% panel reactive antibodies) recipients, who showed an early (2 years) but short-lived benefit. The benefit of receiving a HLA-A, -B, and -DR 0MM shipped kidney remained strong and statistically significant (0.71 relative risk of graft loss vs. local; POrgan Sharing policy restricting mandated sharing of 0MM kidneys to sensitized and pediatric recipients will give greater flexibility to the local organ procurement organization in allocating organs. However, the survival benefit to nonsensitized patients is real and long lasting and will be lost.

  18. The subset of patients with acute heart failure able to secrete relaxin-2 at pregnancy concentrations could have a longer survival: a pilot study.

    Science.gov (United States)

    Miró, Òscar; Herrero-Puente, Pablo; Prieto, Belén; García-García, María; García-Hernández, Pablo; Martín-Sánchez, Francisco J; Jacob, Javier; Ríos, José; Romero, Rodolfo; Gil, Víctor; Gayat, Étienne; Llorens, Pere; Mebazaa, Alexandre

    2018-05-01

    To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome. In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 10 days), combined endpoint (death, rehospitalisation, ED revisit) 30 days after discharge, and 30-day, one-year and three-year death rates. We included 814 patients [81 (SD = 9) years; 53.0% women] followed during 1.9 (SD 2.8) years; 517 (63.5%) died. Twenty patients (2.5%) formed the PLG (median relaxin-2 = 1459 pg/mL; IQR = 1722) and 794 the CG (median = 26; IQR = 44). There was no interaction with variables included on adjustment (age, sex, ischaemic cardiomyopathy, NT-proBNP, glycaemia, and sodium). PLG patients did not have better short-term secondary endpoints, but did show a significantly lower three-year mortality [OR adjusted  = 0.17 (0.05-0.5), p = 0.003]. The small proportion of AHF patients achieving relaxin-2 concentrations similar to those observed in pregnancy may survive longer.

  19. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

    Science.gov (United States)

    Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

    2014-04-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Survival of Lymphatic Cells after X-Irradiation in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Vos, O. [Medical Biological Laboratory, National Defense Research Organization TNO, Ruswuk, Z.H. (Netherlands)

    1967-07-15

    Lymphatic tissues are generally classified among the most radiosensitive tissues of the body. The main reason for this is that histologically extensive destruction is found within a few hours after irradiation. We tried to estimate the degree of cellular degeneration by making cell suspensions from lymph nodes and thymus of mice at different times after X-irradiation with 800 R or at 24 h after radiation with different doses. The numbers of normal viable cells we obtained were expressed as percentages of the cells recovered from unirradiated control mice.

  1. Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

    Science.gov (United States)

    Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

    1994-10-01

    Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

  2. Effect of blood transfusion and cyclophosphamide on cardiac allograft survival in sensitized mice

    International Nuclear Information System (INIS)

    Lasek, Witold; Sora, Magdalena; Jakobisiak, Marek

    1994-01-01

    In the H-2-incompatible donor-recipient model in mice (BALB/c → CBA/H), combination of donor-specific blood transfusion (DST) on the day -9 before transplantation with both pre- and post transplant immunosuppression with cyclophosphamide (CY) interacted beneficially to produce significant donor-specific prolongation of cardiac graft survival. However, in recipients presensitized with donor-specific blood on the day -21, combination of DST with pre- and post transplant CY immunosuppression did not act synergistically and graft survival in this group did not differ from that in presentized mice treated with 2 doses of CY alone. (author). 21 refs, 1 fig., 3 tabs

  3. Survival of tumor-bearing mice exposed to heavy water or heavy water plus methotrexate

    International Nuclear Information System (INIS)

    Laissue, J.A.; Buerki, H.; Berchtold, W.

    1982-01-01

    Moderate body deuteration combined with a cytostatic drug [methotrexate (MTX)] significantly increases the survival time of young adult DBA/2 mice bearing transplantable P815. L5178Y, or L1210 tumors. Neoplastic cells were grown in vitro from tumor stock and injected i.p. into mice from two groups, one drinking tap water, and other drinking 30% heavy water in tap water. One-half of the animals in each of these two groups was given a single injection of MTX (4 mg/kg body weight) on 3 consecutive days per week. At death, extension of primary and metastatic tumors was examined and was found to be macro- and microscopically comparable in the corresponding groups. The mean survival time of untreated mice drinking tap water was about 2 weeks following injection of the fast-growing P815, L5178Y, or L1210 (V) tumors and approximately 5 weeks after injection of cells from a slower-growing L1210 subline. Body deuteration alone roughly doubled the survival time solely of mice bearing this L1210 subline. Treatment with MTX approximately doubled the mean survival time of hosts bearing one of the fast-growing tumors. Combined treatment with heavy water and MTX increased the mean survival time of the mice in all groups by 15 to 125% as compared to control values. The reasons for this effect are unknown. However, heavy water has been shown to exert antimitotic activity and to depress the incorporation of radioactive precursors into DNA of proliferating mammalian cells. The depression of antibody formation following antigenic stimulation and the reduction in numbers of nonneoplastic lymphoid cells of mice following moderate body deuteration may have contributed to the enhancement of MTX activity in addition to other effects of deuterium

  4. Biochemical aspects of the immunomodular action in irradiated survival mice with 60C gama irradiation

    International Nuclear Information System (INIS)

    Garcia Agudo, N.L. del M. de.

    1983-01-01

    The radioprotective action of Calmetti-Guerin bacillus (BCG), Corynebacterium parvum, Escherichia coli Lipopolysccharides (LPS) and peptone proteose was evaluated. A single injection of the macrophage activiting agents prior to 60 Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.) [pt

  5. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

    Science.gov (United States)

    Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-12-22

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

  6. Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

    OpenAIRE

    Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

    2018-01-01

    Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

  7. Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice.

    Science.gov (United States)

    Beli, Eleni; Yan, Yuanqing; Moldovan, Leni; Vieira, Cristiano P; Gao, Ruli; Duan, Yaqian; Prasad, Ram; Bhatwadekar, Ashay; White, Fletcher A; Townsend, Steven; Chan, Luisa; Ryan, Caitlin N; Morton, Daniel; Moldovan, Emil G; Chu, Fang-I; Oudit, Gavin Y; Derendorf, Hartmut; Adorini, Luciano; Wang, Xiaoxin X; Evans-Molina, Carmella; Mirmira, Raghavendra G; Boulton, Michael E; Yoder, Mervin C; Li, Qiuhong; Levi, Moshe; Busik, Julia V; Grant, Maria B

    2018-04-30

    Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR endpoints, including acellular capillaries and leukocyte infiltration. We hypothesized that IF mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia Compared to db/db mice on ad-libitum (AL) feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number and villi length and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR-5, the TUDCA receptor, was found in neural cells of the retina primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a key downstream target of TGR-5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota towards species producing TUDCA and subsequent retinal protection by TGR5 activation. © 2018 by the American Diabetes Association.

  8. Tanacetum parthenium leaf extract mediated survival protection in lethally irradiated Swiss albino mice

    International Nuclear Information System (INIS)

    Shetty, Prashanth; Pooja, S.; Suchetha Kumari, N.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.

    2016-01-01

    Search for less-toxic radioprotectors has spurred interest in the development of natural products. In Ayurveda, the traditional medicine, Tanacetum species have been used to treat ailments since ancient times throughout the world. Effects of the administration of different concentrations of Tanacetum parthenium leaf aqueous extract (TPLA), Tanacetum parthenium leaf ethanolic extract (TPLE) were investigated in Swiss albino mice. Mice (20-25 g) were randomly divided into 8 groups of ten animals each. The control group and the radiation group were treated daily with oral administration of saline for 15 days. Each subgroups of TPLA and TPLE were treated with doses of 50, 100 and 250 mg/kg daily for 15 days. On the 15th day, all were irradiated with 10 Gy whole body irradiation. Survival was observed daily up to 30th post-irradiation day. Data were analysed using the Kaplan-Meier survival curves. The significance difference in survival between control, radiation and treatment groups were observed (P < 0.001). Current studies revealed the protective effect of Tanacetum parthenium rendering high survivability in lethally irradiated mice. (author)

  9. The polymorphism IL-1 beta T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

    DEFF Research Database (Denmark)

    Vangsted, A.J.; Klausen, T.W.; Ruminski, W.

    2009-01-01

    high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1 beta T-31C significantly influenced overall survival (OS; P = 0.02) and that carriers...

  10. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-01-01

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-11-01

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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  13. Where do people live longer and shorter lives? An ecological study of old-age survival across 4404 small areas from 18 European countries.

    Science.gov (United States)

    Ribeiro, Ana Isabel; Krainski, Elias Teixeira; Carvalho, Marilia Sá; Pina, Maria de Fátima de

    2016-06-01

    Further increases in life expectancy in high-income countries depend to a large extent on advances in old-age survival. We aimed to characterise the spatial distribution of old-age survival across small areas of Europe, and to identify areas with significantly high or low survivorship. This study incorporated 4404 small areas from 18 European countries. We used a 10-year survival rate to express the proportion of population aged 75-84 years who reached 85-94 years of age (beyond average life expectancy). This metric was calculated for each gender using decennial census data (1991, 2001 and 2011) at small geographical areas. To address problems associated with small areas, rates were smoothed using a Bayesian spatial model. Excursion sets were defined to identify areas with significantly high (>95th centile) and low (exist, suggesting that European social unity is still to be accomplished. These inequalities could arise from a myriad of population health determinants (eg, poverty, unhealthy lifestyles), which merit further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1976-01-01

    Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2/sup d/ and H-2/sup b/, respectively). Infusion of 10 7 (C57BL/Ka x Balb/c)F 1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation

  15. Longer dialysis session length is associated with better intermediate outcomes and survival among patients on in-center three times per week hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

    Science.gov (United States)

    Tentori, Francesca; Zhang, Jinyao; Li, Yun; Karaboyas, Angelo; Kerr, Peter; Saran, Rajiv; Bommer, Juergen; Port, Friedrich; Akiba, Takashi; Pisoni, Ronald; Robinson, Bruce

    2012-11-01

    Longer dialysis session length (treatment time, TT) has been associated with better survival among hemodialysis (HD) patients. The impact of TT on clinical markers that may contribute to this survival advantage is not well known. Using data from the international Dialysis Outcomes and Practice Patterns Study, we assessed the association of TT with clinical outcomes using both standard regression analyses and instrumental variable approaches. The study included 37,414 patients on in-center HD three times per week with prescribed TT from 120 to 420 min. Facility mean TT ranged from 214 min in the USA to 256 min in Australia-New Zealand. Accounting for country effects, mortality risk was lower for patients with longer TT {hazard ratio for every 30 min: all-cause mortality: 0.94 [95% confidence interval (CI): 0.92-0.97], cardiovascular mortality: 0.95 (95% CI: 0.91-0.98) and sudden death: 0.93 (95% CI: 0.88-0.98)}. Patients with longer TT had lower pre- and post-dialysis systolic blood pressure, greater intradialytic weight loss, higher hemoglobin (for the same erythropoietin dose), serum albumin and potassium and lower serum phosphorus and white blood cell counts. Similar associations were found using the instrumental variable approach, although the positive associations of TT with weight loss and potassium were lost. Favorable levels of a variety of clinical markers may contribute to the better survival of patients receiving longer TT. These findings support longer TT prescription in the setting of in-center, three times per week HD.

  16. Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

    Science.gov (United States)

    Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

    2015-10-01

    Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

    Directory of Open Access Journals (Sweden)

    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  18. Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

    Science.gov (United States)

    Pini, Maria; Rhodes, Davina H.; Castellanos, Karla J.; Cabay, Robert J.; Grady, Eileen F.; Fantuzzi, Giamila

    2012-01-01

    Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice. PMID:22815875

  19. Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

    Directory of Open Access Journals (Sweden)

    Qing-rong WANG

    2017-02-01

    Full Text Available Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

  20. Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.

    Science.gov (United States)

    Li, Jinhua; Theofanous, Leigh; Stickel, Sara; Bouton-Verville, Hilary; Burgin, Kelly E; Jakubchak, Susan; Wagner, Thomas E; Wei, Yanzhang

    2007-07-01

    Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.

  1. Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation

    International Nuclear Information System (INIS)

    Bichay, T.J.E.; Roy, R.M.

    1986-01-01

    The LD 50/30 of CD-1-female mice increased from 6.6 Gy to 7.0 Gy when 2.5 mg of dl-α-tocopherol was injected immediately post irradiation. Increased survival was associated with increased numbers of hematopoietic colony forming units (CFU). Endogeneous spleen colonies were found in greater numbers in the tocopherol-treated mice after irradiation. The vitamin, however, must be injected within five hours following irradiation to have this effect. The increased numbers of CFU in tocopherol-treated mice may be due to a stimulation of recovery of repair processes. Split-dose studies suggest that most repair of sublethal damage in hematopoietic stem cells take place within seven and nine hours following irradiation. Tocopherol injection appears to enhance the recovery manifested in the split-dose assay. There is also evidence that tocopherol-treatment caused an earlier onset of mitotic activity in CFU after irradiation. The increased number of spleen colonies in tocopherol-injected mice is not due to an altered CFU seeding efficiency associated with an altered spleen microenvironment. Tocopherol injection did not affect the shoulder of the stem cell survival curve using exogenous spleen colony assays of bone marrow-derived or spleen-derived hematopoietic stem cells. There appears to be a decrease in D 0 in the higher dose region (4.3 Gy) of the bone marrow exogenous SCA survival curves for the vehicle-injected and the non-injected groups; however, the tocopherol-injected group showed no evidence of change in radiosensitivity up to the highest dose used (5.0 Gy). Data may be interpreted to suggest that the therapeutic effect of tocopherol may involve repair of hematopoietic stem cell damage in the higher dose range of bone marrow syndrome. (orig.) [de

  2. Neural androgen receptors affect the number of surviving new neurones in the adult dentate gyrus of male mice.

    Science.gov (United States)

    Swift-Gallant, A; Duarte-Guterman, P; Hamson, D K; Ibrahim, M; Monks, D A; Galea, L A M

    2018-04-01

    Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurones within the hippocampus is modulated by the action of androgen via the androgen receptor (AR); however, it is not known whether this holds true in mice. Furthermore, the evidence is mixed regarding whether androgens act in neural tissue or via peripheral non-neural targets to promote new neurone survival in the hippocampus. We evaluated whether the action of androgen via AR underlies the survival of new neurones in mice, and investigated whether increasing AR selectively in neural tissue would increase new neurone survival in the hippocampus. We used the cre-loxP system to overexpress AR only in neural tissues (Nestin-AR). These males were compared with wild-type males, as well as control males with 1 of the 2 mutations required for overexpression. Mice were gonadectomised and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, proliferation (Ki67) and survival (BrdU) of new neurones were both evaluated in the dorsal and ventral dentate gyrus. Dihydrotestosterone treatment increased the survival of new neurones in the entire hippocampus in wild-type mice and control mice that only have 1 of 2 necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurones in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wild-type or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neurone survival is nonlinear. © 2018 British Society for Neuroendocrinology.

  3. Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis.

    Science.gov (United States)

    Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P

    1996-12-01

    The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.

  4. The effects of uranium on reproduction, gestation, and postnatal survival in mice

    International Nuclear Information System (INIS)

    Paternain, J.L.; Domingo, J.L.; Ortega, A.; Llobet, J.M.

    1989-01-01

    Uranyl acetate dihydrate was tested for its effects on reproduction, gestation, and postnatal survival in Swiss mice. Four groups of animals, each of which consisted of 25 males and 25 females, were administered 0, 5, 10, and 25 mg/kg/day of uranyl acetate dihydrate. Mature male mice were treated orally for 60 days prior to mating with mature virgin female mice treated orally for 14 days prior to mating. Treatment of the females continued throughout mating, gestation, parturition, and nursing of the litters. One-half of the dams in each group were sacrificed on Day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored after 0, 4, and 21 days of lactation. No adverse effects on fertility were evident at the doses employed in this study. Nevertheless, embryolethality could be observed in the 25 mg/kg/day group. Significant increases in the number of dead young per litter were seen at birth and at Day 4 of lactation in the 25 mg/kg/day group. The growth of the offspring was always significantly lower for the uranium-treated animals. However, the present results suggest that uranium does not cause any adverse effects on fertility, general reproductive parameters, or offspring survival at the concentrations usually ingested by man

  5. Influence of radiation fractionation on survival of mice and spleen colony-forming units

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Bullis, J.E.

    1994-01-01

    C57B1/6 mice were given Gy X-rays fractionated in several ways. There was a cyclical pattern of animal survival which was correlated to the fractionation interval and which indicated a periodicity of 6 h. Ten grays given a single dose is fatal to 100% of the mice and depresses the CFU-S to about one per leg with no evidence of proliferation during the remaining life. Ten grays given in 2.5-Gy increments at 24-h intervals causes no fatalities and results in a similar CFU-S depression but is followed by an exponential increase in CFU-S over the ensuing 12 days. Although bone marrow from survivors of such treatment was comparable to control marrow in its capacity for short-term rescue, it was clearly, inferior in its capability for long-term rescue. The periodicity of 6 h suggests that the cells responsible for survival of the mice have been synchronized into more or less radiosensitive and radioresistant stages of the cell cycle as a result of the time between the 25-Gy increments. Implications for the CFU-S and long-term repopulating cells are discussed. 22 refs., 5 figs., 1 tab

  6. Prolonged minor allograft survival in intravenously primed mice--a test of the veto hypothesis

    International Nuclear Information System (INIS)

    Johnson, L.L.

    1987-01-01

    Experiments were performed to test the hypothesis that veto cells are responsible for the prolonged survival of minor allografts of skin that is observed in recipients primed intravenously with spleen cells from mice syngeneic with the skin donors. This prolonged survival was observed for each of several minor histocompatibility (H) antigens and is antigen-specific. Gamma radiation (3300 rads) abolished the ability of male spleen cells infused i.v. to delay the rejection of male skin grafts (H-Y antigen) on female recipients. However, depletion of Thy-1+ cells from the i.v. infusion failed to abolish the ability to prolong male skin graft survival. Furthermore, the prolonged survival accorded to B6 (H-2b) male skin grafts on CB6F1 (H-2b/H-2d) female recipients given i.v. infusions of B6 male spleen cells extended to BALB/c (H-2d) male skin grafts as well, indicating a lack of MHC restriction. Thus, prolongation of minor allograft survival by i.v. infusion of minor H antigen-bearing spleen cells appears not to depend on veto T cells that others have found to be responsible for the suppression of CTL generation

  7. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Directory of Open Access Journals (Sweden)

    Saher Hamed

    Full Text Available BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF-treated and phosphate-buffered saline (PBS-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  8. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Science.gov (United States)

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-11-15

    Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  9. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2014-09-12

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

  10. Effects of imidazole derivatives in the survival of 60Co irradiated mice

    International Nuclear Information System (INIS)

    Villavicencio, A.L.C.H.; Mastro, N.L. del.

    1988-07-01

    The presence of hypoxic and radioresistant cells is considered the main reason of failure in radiotherapy of neoplasms. Hypoxic cell radiosensitizers, as nitroimidazole derivatives, have an advantage over other alternative methods for improving the effects of radiotherapy since hypoxic cells exist in considerable concentration in tumours and only in small concentration in normal tissues. Its show also a direct cytotoxicity over the hypoxic cell population. In this work, studies on combining ip administered drugs and single dose radiation treatments in healthy albino mice are presented. It was compared the action of 2-nitroimidazole, levamisole and cysteine, the latest considered as radioprotector for several biological systems. The results showed some radioprotective action for 2 - nitroimidazole (MISO), sensitizer capacity for levamisole and in those conditions, cysteine failed to produce any effects on the survival of 9 Gy 60 Co irradiated mice. (author) [pt

  11. Administration of polysaccharide from Panax notoginseng prolonged the survival of H22 tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Li HY

    2016-06-01

    Full Text Available Huaiyu Li,1,* Longlong Gu,1,2,* Yuanyuan Zhong,1 Yajuan Chen,1 Lei Zhang,1 Annie R Zhang,3 Robert W Sobol,4,5 Tong Chen,1,6 Jianfeng Li4,5 1Yunnan Key Laboratory of Pharmacology for Natural Products, School of Pharmaceutical Sciences, 2Haiyuan College, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Graduate School of Applied and Professional Psychology, Rutgers, The State University of New Jersey, Piscataway, NJ, 4Department of Oncologic Sciences, 5Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA; 6Yunnan Panax notoginseng (Burk F.H. Chen Biotechnology and Pharmaceutical Engineering Research Center, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this work Background: Polysaccharides from various sources are being considered potential sources for the treatment of liver cancer. The aim of this study was to investigate the impact of polysaccharide isolated from Panax notoginseng (PPN on the proliferation of H22 liver cancer cells and the survival of the tumor-bearing mice transplanted with H22 cells.Materials and methods: Polysaccharide from PPN was added to the culture medium of mouse hepatoma H22 cells at different doses. Cell proliferation was assayed with a standard MTT assay. Survival rates of tumor-bearing mice were recorded. Peripheral blood lymphocytes were assayed by flow cytometry. Serum interleukin-2 levels in peripheral blood were measured by enzyme-linked immunosorbent assay.Results: Polysaccharide from PPN inhibited the growth of H22 cells and significantly prolonged the survival of tumor-bearing mice. The increase in activated CD4+ T-cells and the elevation of serum interleukin-2 may contribute to the antitumor activity of PPN.Conclusion: PPN has potential antitumor activity for the treatment of liver cancer. Keywords: polysaccharide, Panax notoginseng, liver cancer, immunotherapy, IL-2

  12. Minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during Plasmodium berghei ANKA infection.

    Science.gov (United States)

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash

    2017-02-01

    Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study. Infected mice were treated with an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days that led to parasite clearance in blood, brain, liver and spleen on 7th day post-infection; and the mice survived until experiment ended (90days) without parasite recrudescence. Evans blue extravasation assay showed that blood-brain barrier integrity was maintained by minocycline. The tumor necrosis factor-alpha protein level and caspase activity, which is related to CM pathogenesis, was significantly reduced in the minocycline-treated group. Fluoro-Jade® C and hematoxylin-eosin staining of the brains of minocycline group revealed a decrease in degenerating neurons and absence of hemorrhages respectively. Minocycline treatment led to decrease in gene expressions of inflammatory mediators like interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence decrease in T-cell-mediated cerebral inflammation. We also proved that this reduction in gene expressions is irrespective of the anti-parasitic property of minocycline. The distinct ability of minocycline to modulate gene expressions of CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as chemoprophylaxis. Our study shows that minocycline is highly effective in conferring neuroprotection during ECM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The effect of natural hot environment on survival and peripheral blood lymphocytes in γ-irradiated mice

    International Nuclear Information System (INIS)

    Zhou Meijuan; Zheng Li; Ding Zhenhua

    2004-01-01

    Objective: To study the effect of natural hot environment (NHE) on survival and peripheral blood lymphocytes in γ-irradiated in mice. Methods: After γ-irradiation at the dosage of 6.5 or 9.0 Gy, the mice were exposed to NHE for 0, 3, 6, 9 h or 30 days. After exposure to NHE, mice of the 6 h and 9 h groups, were then bred at room temperature. The survival and peripheral blood lymphocytes were observed for 30 days. Results: There were obvious differences in survival time between the groups that were exposed to NHE for 9 h and 30 d and that of the 0 h group, the mice of these three groups having been irradiated with 6.5 Gy. For 9.0 Gy-irradiated mice, the survival times of the 6, 9 h and 30 d groups were all significantly shorter than that of the 0 h group. The descending rate of peripheral blood lymphocytes in 0 h group is smaller than that of all NHE groups. There was no lymphocyte fluctuate resuscitation in all NHE groups as seen in the 0 h group. Conclusion: There is a significant decrease of survival indexes and a faster descending rate of peripheral blood lymphocytes in mice exposed to after γ-irradiation. (authors)

  14. The effects of polymeric plutonium on erythrocyte survival in mice, (1)

    International Nuclear Information System (INIS)

    Joshima, Hisamasa; Kashima, Masatoshi; Matsuoka, Osamu

    1976-01-01

    The changes in erythrocyte counts, hematocrit, hemoglobin, reticulocyte counts and erythrocyte survival following an intravenous injection of polymeric 239 Pu at the dose level of 15 μCi/kg, 10 μCi/kg and 5 μCi/kg were studied in CF no. 1 male mice in order to investigate the possible pathogenesis of anemia produced by irradiation of polymeric plutonium. The administration of 15 μCi/kg and 10 μCi/kg of polymeric plutonium produced anemia but 5 μCi/kg had no significant effect. Studies with 51 Cr labelled erythrocyte showed a moderate reduction in survival of erythrocyte following a single intraveneous injection of polymeric plutonium. Not only the intracorpuscular effect but also extracorpuscular effect of polymeric plutonium was considered to lead to a reduction in erythrocyte survival, but no clear dose relationship could be observed between the reduction of survival and either intracorpuscular effect or extracorpuscular effect. Although the most important pathogenesis of anemia produced by polymeric plutonium is supposed to be a decreased erythropoiesis, it was believed that both qualitatively impaired erythropoiesis and abnormal erythrocyte destruction might also play some role in the occurrence of anemia. (auth.)

  15. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    Science.gov (United States)

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-07

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

  16. Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice

    Science.gov (United States)

    Koval, Erica D.; Shaner, Carey; Zhang, Peter; du Maine, Xavier; Fischer, Kimberlee; Tay, Jia; Chau, B. Nelson; Wu, Gregory F.; Miller, Timothy M.

    2013-01-01

    microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1)G93A rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1G93A mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS. PMID:23740943

  17. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Directory of Open Access Journals (Sweden)

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  18. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Erica S Martins-Duarte

    Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

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

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Tkadlecek, L.; Viklicka, S.; Pipalova, I.; Hola, J.

    1992-01-01

    An impairment was observed of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of the prostaglandin synthesis inhibitors (PGSIs) indomethacin or diclofenac. Morphological examination of the gastrointestinal tract and estimation of the blood loss into its lumen in animals treated with diclofenac did not show serious damage such as hemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation. (author) 2 tabs., 4 figs., 20 refs

  20. Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice.

    Science.gov (United States)

    Giles, Kurt; Berry, David B; Condello, Carlo; Dugger, Brittany N; Li, Zhe; Oehler, Abby; Bhardwaj, Sumita; Elepano, Manuel; Guan, Shenheng; Silber, B Michael; Olson, Steven H; Prusiner, Stanley B

    2016-09-01

    Developing therapeutics for neurodegenerative diseases (NDs) prevalent in the aging population remains a daunting challenge. With the growing understanding that many NDs progress by conformational self-templating of specific proteins, the prototypical prion diseases offer a platform for ND drug discovery. We evaluated high-throughput screening hits with the aryl amide scaffold and explored the structure-activity relationships around three series differing in their N-aryl core: benzoxazole, benzothiazole, and cyano. Potent anti-prion compounds were advanced to pharmacokinetic studies, and the resulting brain-penetrant leads from each series, together with a related N-aryl piperazine lead, were escalated to long-term dosing and efficacy studies. Compounds from each of the four series doubled the survival of mice infected with a mouse-passaged prion strain. Treatment with aryl amides altered prion strain properties, as evidenced by the distinct patterns of neuropathological deposition of prion protein and associated astrocytic gliosis in the brain; however, none of the aryl amide compounds resulted in drug-resistant prion strains, in contrast to previous studies on compounds with the 2-aminothiazole (2-AMT) scaffold. As seen with 2-AMTs and other effective anti-prion compounds reported to date, the novel aryl amides reported here were ineffective in prolonging the survival of transgenic mice infected with human prions. Most encouraging is our discovery that aryl amides show that the development of drug resistance is not an inevitable consequence of efficacious anti-prion therapeutics. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Influence of diethylmaleate on the survival of irradiated mice and on serum protein levels

    International Nuclear Information System (INIS)

    Bernardes, E.

    1990-01-01

    Glutathione (GSH) is the major of the living plants or animal cell low molecular weight thiol compound which serves as a main endogenous cellular radioprotector. In order to improve radiotherapy, a possible approach should be to try to administrate hypoxic cell radiosensitizers altogether with glutathione intracellular depletors, for example, a binding GSH agent like diethylmaleate (DEM), in an attempt to overcome the neurotoxic side effects while maintaining their radiosensitizing properties. This study was performed to investigate whether the administration of DEM alone could modify the radioresistance of mice as measure by the 30-day-survival after irradiation and to establish whether this modification can be reflected in the murine serum protein profiles. Millimolar concentrations of DEM were dissolved alternatively in commercial peanut oil or absolute ethanol (final concentration 0.27%) and administered to male or female albino mice ip 1 h prior to 9 Gy sup(60) Cowhole-body irradiation with an average dose rate of 5.2 Gy/min. (author)

  2. Recovery of endo-CFU-S in radio-adaptive survival response in mice

    International Nuclear Information System (INIS)

    Yonezawa, Morio; Horie, Kiyohito; Kubo, Kihei

    2003-01-01

    A priming irradiation with 0.45 Gy of X-rays, given 2 weeks prior to the challenging exposures, induces radio-resistance (decrease in bone marrow death rate after mid-lethal irradiations) in mice of C57BL/6 mice. This acquired radio-resistance appeared on day 9 and continued till day 17 after the priming irradiation, with a maximal on days 12-14 and diminished on day 21. The priming irradiation, given 14 days prior to the challenging exposure, increased endogenous spleen colonies on days 12-13 after exposure to 5.0 Gy. Effect of interval time between the priming and the challenging irradiations on the increase in endogenous spleen colonies was also examined. Significant increase of the colonies by the priming irradiation was observed when the interval time was 12-17 and 21 days. The results correspond to the increase of the survival rates on days 12-17 after the challenging irradiations. (author)

  3. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

    Science.gov (United States)

    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  4. Influence of diethyl maleate in irradiated mice survival and related to percentages of serum proteins

    International Nuclear Information System (INIS)

    Bernardes, E.; Mastro, N.L. del

    1990-01-01

    The use of radiomodifying drugs that alter the radiation effect, protecting or sensitizing cells and organisms, presents great interest in tumor radiotherapy. Glutathione (GSH) can be described as the major endogenous radioprotector. The diethyl maleate (DEM) is a drug able to block intracellular GSH. This work aims at the establishment of the radiomodifying competence of DEM administered in two different vehicles, peanut oil and aqueous ethanolic solution by the analysis of mouse survival curves as well as the relative percentages of serum proteins. Groups of animals were previously injected intraperitoneally with 0.3 ml of 418 e 150 μM DEM respectively in each one of the vehicles one hour before irradiated with an 60 Co acute dose of 9 Gy. The survival of mice was followed during 30 days and electrophoretic profiles of serum proteins 1,3 and 7 days after irradiation. The results showed that the action of DEM om mouse radiosensitivity depends on the vehicles used, considering that both media showed a radio modifier action. (author)

  5. Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Claus, Sandrine P; Le Roy, Caroline I; Grangette, Corinne; Pot, Bruno; Martinez, Inés; Walter, Jens; Cani, Patrice D; Delzenne, Nathalie M

    2016-06-01

    Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.

  6. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    Directory of Open Access Journals (Sweden)

    Yosuke Kikuchi

    Full Text Available The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  7. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low

  8. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose

  9. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

    Science.gov (United States)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-06-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

  10. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.

    Directory of Open Access Journals (Sweden)

    Marlen Martinez-Gutierrez

    Full Text Available BACKGROUND: It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV, can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1 × 10(6 plaque-forming units (PFU/ml of DENV-2 and treated with LOV (200 mg/kg/day. Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days. Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses compared to the untreated group (4.8 days. Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.

  11. Survival of tumor bearing mice by sequencing of low dose rate (LDR) neutron and photon radiation

    International Nuclear Information System (INIS)

    Onomura, C.I.; Feola, J.M.; Maruyama, Y.

    1984-01-01

    Cf-252 neutron radiation (NT) has been shown to be effective therapy for bulky, hypoxic human tumor and to produce consistent rapid clearance and 5 year cures. NT has been found to be more or less effective depending upon the schedule in which it is used and upon mixing with photon radiation. In an effort to study this scheduling and photon effect, LSA tumor was irradiated in vivo in a hypoxic, advanced state, in different schedules in combination of NT with Co-60 photons. The LSA lymphoma of C57BL/ym mice represents an accurate system to assess dose-response of tumor cells in vivo. Mean survival time was used as endpoint. A high RBE for LDR Cf-252 NT was observed with a RBE(n) of -- 5.0. The effect was not greatly sensitive to sequence in which photons were used. Comparison studies were also tested relative to LDR Cs-137 photon radiation. The results support the high efficacy of LDR NT for destruction of hypoxic tumor in vivo

  12. Sodium Iodide Symporter PET and BLI Noninvasively Reveal Mesoangioblast Survival in Dystrophic Mice

    Directory of Open Access Journals (Sweden)

    Bryan Holvoet

    2015-12-01

    Full Text Available Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc and the human sodium iodide transporter (hNIS to allow cell monitoring via bioluminescence imaging (BLI and small-animal positron emission tomography (PET. Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells.

  13. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    DEFF Research Database (Denmark)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein....../sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our...... findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue...

  14. Improved survival and marrow engraftment of mice transplanted with bone marrov of GM-CSF-treated donors

    International Nuclear Information System (INIS)

    Ballin, A.; Sagi, O.; Schiby, G.; Meytes, D.

    1993-01-01

    Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 x 105 BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p < 0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, Leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice. (au) (13 refs.)

  15. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were......INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  16. Kinetics of hemopoietic stem cells and survival of mice treated with hydroxyurea and exposed to prolonged γ-radiation

    International Nuclear Information System (INIS)

    Chertkov, K.S.; Rogozkin, V.D.; Dikovenko, E.A.; Mosina, Z.M.

    1979-01-01

    A study was made of radioprotective efficiency of hydroxyurea in relation to mice exposed to prolonged 137 Cs-γ-radiation. It was found that a 30-day survival rate, under optimal conditions of treatment with hydroxyurea, was more than 40 per cent higher than that of the controls. The protective effect of hydroxyurea was manifested at the level of hemopoietic stem cells due to a quicker onset and accelerated rate of the repopulation process

  17. Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice.

    Science.gov (United States)

    Buschemeyer, W Cooper; Klink, Joseph C; Mavropoulos, John C; Poulton, Susan H; Demark-Wahnefried, Wendy; Hursting, Stephen D; Cohen, Pinchas; Hwang, David; Johnson, Tracy L; Freedland, Stephen J

    2010-07-01

    Caloric restriction (CR) delays cancer growth in animals, though translation to humans is difficult. We hypothesized intermittent fasting (i.e., intermittent extreme CR), may be better tolerated and prolong survival of prostate cancer (CaP) bearing mice. We conducted a pilot study by injecting 105 male individually-housed SCID mice with LAPC-4 cells. When tumors reached 200 mm(3), 15 mice/group were randomized to one of seven diets and sacrificed when tumors reached 1,500 mm(3): Group 1: ad libitum 7 days/week; Group 2: fasted 1 day/week and ad libitum 6 days/week; Group 3: fasted 1 day/week and fed 6 days/week via paired feeding to maintain isocaloric conditions to Group 1; Group 4: 14% CR 7 days/week; Group 5: fasted 2 days/week and ad libitum 5 days/week; Group 6: fasted 2 day/week and fed 5 days/week via paired feeding to maintain isocaloric conditions to Group 1; Group 7: 28% CR 7 days/week. Sera from mice at sacrifice were analyzed for IGF-axis hormones. There were no significant differences in survival among any groups. However, relative to Group 1, there were non-significant trends for improved survival for Groups 3 (HR 0.65, P = 0.26), 5 (0.60, P = 0.18), 6 (HR 0.59, P = 0.16), and 7 (P = 0.59, P = 0.17). Relative to Group 1, body weights and IGF-1 levels were significantly lower in Groups 6 and 7. This exploratory study found non-significant trends toward improved survival with some intermittent fasting regimens, in the absence of weight loss. Larger appropriately powered studies to detect modest, but clinically important differences are necessary to confirm these findings.

  18. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    International Nuclear Information System (INIS)

    Christofidou-Solomidou, Melpo; Cengel, Keith A; Tyagi, Sonia; Tan, Kay-See; Hagan, Sarah; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Heitjan, Daniel F; Solomides, Charalambos C

    2011-01-01

    Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease

  19. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    Directory of Open Access Journals (Sweden)

    Arguiri Evguenia

    2011-06-01

    Full Text Available Abstract Background Flaxseed (FS is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD. Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT. However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. Methods We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6 in 2 separate experiments (n = 15-25 mice/group on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Results Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not, maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the

  20. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Christofidou-Solomidou, Melpo [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Cengel, Keith A [Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Tyagi, Sonia [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Tan, Kay-See [Biostatistics & Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Hagan, Sarah [Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Heitjan, Daniel F [Biostatistics & Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Solomides, Charalambos C [Department of Pathology, Jefferson University Hospital, Philadelphia, PA 19140 (United States)

    2011-06-24

    Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of

  1. Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice.

    Science.gov (United States)

    Kang, Xiangpeng; Chen, Jibing; Qin, Qing; Wang, Feng; Wang, Yongzhi; Lan, Tianshu; Xu, Shuo; Wang, Feiyu; Xia, Junjie; Ekberg, Henrik; Qi, Zhongquan; Liu, Zhongchen

    2010-05-01

    Memory T cells present a unique challenge in transplantation. Although memory T cells express robust immune responses to invading pathogens, they may be resistant to the effects of immunosuppressive therapies used to prolong graft survival. In previous studies, we found that compound K, the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., reduced acute cardiac allograft rejection in mice (Wang et al., 2009 [1]). Here, we further investigated the effect of compound K on cardiac allograft rejection in alloantigen-primed mice. We found that compound K significantly inhibited CD4(+) and CD8(+) memory T cells proliferation in a mixed lymphocyte reaction (MLR). In vivo, compound K combined with anti-CD154 and anti-LFA-1 monoclonal antibodies (mAbs) significantly extended the survival time of heart grafts in alloantigen-primed mice with no obvious toxic side effects. Furthermore, our data suggests that compound K works by reducing the expression of both IL-2 and IFN-gamma within the graft rather than enhancing expression of regulatory T cells (Tregs). Compound K can also inhibit the alloresponses of memory T cells, while increasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing the level of alloantibodies in the serum. Our study highlights the unique immune effects of compound K that may be further explored for clinical use in extending the survival of transplant grafts. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  2. Schistosoma mansoni: quantitative aspects of the fertility and survival of worms obtained from irradiated cercariae (3 Krad), in mice

    International Nuclear Information System (INIS)

    Sa Cardoso, G. de; Coelho, P.M.Z.

    1990-01-01

    The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus), experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains), by transcutaneous route. The cercariae used were a) non-irradiated (control groups), and b) irradiated with 3 Krad of gamma irradiation (Co-60). From the 33 rd day on, some stability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90 th day), notedly in relation to the LE strain . Thus, it was concluded that gamma irradiation (at the dose of 3 Krad) is able to hinder the worm egg production in 98.1% of the infected mice. Further, it was observed that the few detected eggs were dead. Females were found to be more resistant to irradiation. The irradiation effect on the mortality of male worms was statistically significant scarcely from the 61 st day on. The long period of permanence of the sterile adult irradiated worms in the portal system of mice and their probable involvement in the development of immuno-protection (the so-called concomitant immunity, without the immuno-pathological involvements for the host) are here discussed. (author)

  3. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

    International Nuclear Information System (INIS)

    Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

  4. Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

    Science.gov (United States)

    DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

  5. Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus.

    Science.gov (United States)

    Song, Jeong Ah; Kim, Hee Joo; Hong, Seong Keun; Lee, Dong Hoon; Lee, Sang Won; Song, Chang Seon; Kim, Ki Taek; Choi, In Soo; Lee, Joong Bok; Park, Seung Yong

    2016-02-01

    Influenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection. Mice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined. Because of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group. These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection. Copyright © 2014. Published by Elsevier B.V.

  6. Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Zhu Shijie

    2010-01-01

    Full Text Available Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18, while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1 from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW and organ weights including heart (HW, lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4% was significantly improved compared with group A, B or D (0% of each, P < 0.05. HW and HW/BW ratio in group C was significantly (P < 0.05 lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

  7. Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

    Directory of Open Access Journals (Sweden)

    Gotkine Marc

    2013-01-01

    Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

  8. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    International Nuclear Information System (INIS)

    Zeng, Jing; See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob; Durham, Nicholas; Meyer, Christian; Harris, Timothy J.; Albesiano, Emilia; Pradilla, Gustavo; Ford, Eric; Wong, John; Hammers, Hans-Joerg; Mathios, Dimitris; Tyler, Betty; Brem, Henry; Tran, Phuoc T.; Pardoll, Drew; Drake, Charles G.

    2013-01-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  9. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Durham, Nicholas [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Meyer, Christian [Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Harris, Timothy J. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Albesiano, Emilia; Pradilla, Gustavo [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Ford, Eric; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Hammers, Hans-Joerg [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Mathios, Dimitris; Tyler, Betty; Brem, Henry [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Pardoll, Drew; Drake, Charles G. [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  10. Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus

    International Nuclear Information System (INIS)

    Kimura, Takashi; Griffin, Diane E.

    2003-01-01

    Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4 + T cells showed less tissue loss, while mice lacking CD8 + T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4 + and CD8 + T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4 + cells and macrophage/microglial cells, but not CD8 + cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4 + T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus

  11. Compared to Sucrose, Previous Consumption of Fructose and Glucose Monosaccharides Reduces Survival and Fitness of Female Mice123

    Science.gov (United States)

    Ruff, James S; Hugentobler, Sara A; Suchy, Amanda K; Sosa, Mirtha M; Tanner, Ruth E; Hite, Megumi E; Morrison, Linda C; Gieng, Sin H; Shigenaga, Mark K; Potts, Wayne K

    2015-01-01

    Background: Intake of added sugar has been shown to correlate with many human metabolic diseases, and rodent models have characterized numerous aspects of the resulting disease phenotypes. However, there is a controversy about whether differential health effects occur because of the consumption of either of the two common types of added sugar—high-fructose corn syrup (fructose and glucose monosaccharides; F/G) or table sugar (sucrose, a fructose and glucose disaccharide). Objectives: We tested the equivalence of sucrose- vs. F/G-containing diets on mouse (Mus musculus) longevity, reproductive success, and social dominance. Methods: We fed wild-derived mice, outbred mice descended from wild-caught ancestors, a diet in which 25% of the calories came from either an equal ratio of F/G or an isocaloric amount of sucrose (both diets had 63% of total calories as carbohydrates). Exposure lasted 40 wk, starting at weaning (21 d of age), and then mice (104 females and 56 males) were released into organismal performances assays—seminatural enclosures where mice competed for territories, resources, and mates for 32 wk. Within enclosures all mice consumed the F/G diet. Results: Females initially fed the F/G diet experienced a mortality rate 1.9 times the rate (P = 0.012) and produced 26.4% fewer offspring than females initially fed sucrose (P = 0.001). This reproductive deficiency was present before mortality differences, suggesting the F/G diet was causing physiologic performance deficits prior to mortality. No differential patterns in survival, reproduction, or social dominance were observed in males, indicating a sex-specific outcome of exposure. Conclusion: This study provides experimental evidence that the consumption of human-relevant levels of F/G is more deleterious than an isocaloric amount of sucrose for key organism-level health measures in female mice. PMID:25733457

  12. Compared to sucrose, previous consumption of fructose and glucose monosaccharides reduces survival and fitness of female mice.

    Science.gov (United States)

    Ruff, James S; Hugentobler, Sara A; Suchy, Amanda K; Sosa, Mirtha M; Tanner, Ruth E; Hite, Megumi E; Morrison, Linda C; Gieng, Sin H; Shigenaga, Mark K; Potts, Wayne K

    2015-03-01

    Intake of added sugar has been shown to correlate with many human metabolic diseases, and rodent models have characterized numerous aspects of the resulting disease phenotypes. However, there is a controversy about whether differential health effects occur because of the consumption of either of the two common types of added sugar-high-fructose corn syrup (fructose and glucose monosaccharides; F/G) or table sugar (sucrose, a fructose and glucose disaccharide). We tested the equivalence of sucrose- vs. F/G-containing diets on mouse (Mus musculus) longevity, reproductive success, and social dominance. We fed wild-derived mice, outbred mice descended from wild-caught ancestors, a diet in which 25% of the calories came from either an equal ratio of F/G or an isocaloric amount of sucrose (both diets had 63% of total calories as carbohydrates). Exposure lasted 40 wk, starting at weaning (21 d of age), and then mice (104 females and 56 males) were released into organismal performances assays-seminatural enclosures where mice competed for territories, resources, and mates for 32 wk. Within enclosures all mice consumed the F/G diet. Females initially fed the F/G diet experienced a mortality rate 1.9 times the rate (P = 0.012) and produced 26.4% fewer offspring than females initially fed sucrose (P = 0.001). This reproductive deficiency was present before mortality differences, suggesting the F/G diet was causing physiologic performance deficits prior to mortality. No differential patterns in survival, reproduction, or social dominance were observed in males, indicating a sex-specific outcome of exposure. This study provides experimental evidence that the consumption of human-relevant levels of F/G is more deleterious than an isocaloric amount of sucrose for key organism-level health measures in female mice. © 2015 American Society for Nutrition.

  13. Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Yuan Yan Sin

    2018-03-01

    Full Text Available Progress in gene editing research has been accelerated by utilizing engineered nucleases in combination with induced pluripotent stem cell (iPSC technology. Here, we report transcription activator-like effector nuclease (TALEN-mediated reincorporation of Arg1 exons 7 and 8 in iPSCs derived from arginase-1-deficient mice possessing Arg1Δ alleles lacking these terminal exons. The edited cells could be induced to differentiate into hepatocyte-like cells (iHLCs in vitro and were subsequently used for transplantation into our previously described (Sin et al., PLoS ONE 2013 tamoxifen-inducible Arg1-Cre arginase-1-deficient mouse model. While successful gene-targeted repair was achieved in iPSCs containing Arg1Δ alleles, only minimal restoration of urea cycle function could be observed in the iHLC-transplanted mice compared to control mice, and survival in this lethal model was extended by up to a week in some mice. The partially rescued phenotype may be due to inadequate regenerative capacity of arginase-1-expressing cells in the correct metabolic zones. Technical hurdles exist and will need to be overcome for gene-edited iPSC to iHLC rescue of arginase-1 deficiency, a rare urea cycle disorder.

  14. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

    DEFF Research Database (Denmark)

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin

    2016-01-01

    /BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21...

  15. Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice.

    Science.gov (United States)

    Ryu, Hoon; Smith, Karen; Camelo, Sandra I; Carreras, Isabel; Lee, Junghee; Iglesias, Antonio H; Dangond, Fernando; Cormier, Kerry A; Cudkowicz, Merit E; Brown, Robert H; Ferrante, Robert J

    2005-06-01

    Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium phenylbutyrate, significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice. Phenylbutyrate administration ameliorated histone hypoacetylation observed in G93A mice and induced expression of nuclear factor-kappaB (NF-kappaB) p50, the phosphorylated inhibitory subunit of NF-kappaB (pIkappaB) and beta cell lymphoma 2 (bcl-2), but reduced cytochrome c and caspase expression. Curcumin, an NF-kappaB inhibitor, and mutation of the NF-kappaB responsive element in the bcl-2 promoter, blocked butyrate-induced bcl-2 promoter activity. We provide evidence that the pharmacological induction of NF-kappaB-dependent transcription and bcl-2 gene expression is neuroprotective in ALS mice by inhibiting programmed cell death. Phenylbutyrate acts to phosphorylate IkappaB, translocating NF-kappaB p50 to the nucleus, or to directly acetylate NF-kappaB p50. NF-kappaB p50 transactivates bcl-2 gene expression. Up-regulated bcl-2 blocks cytochrome c release and subsequent caspase activation, slowing motor neuron death. These transcriptional and post-translational pathways ultimately promote motor neuron survival and ameliorate disease progression in ALS mice. Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS.

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

    Science.gov (United States)

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

    2012-05-01

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

  17. Pretreatment with Cry1Ac Protoxin Modulates the Immune Response, and Increases the Survival of Plasmodium-Infected CBA/Ca Mice

    Directory of Open Access Journals (Sweden)

    Martha Legorreta-Herrera

    2010-01-01

    Full Text Available Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal and P. chabaudi AS (nonlethal parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies.

  18. Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice. Dosage and the window of time

    International Nuclear Information System (INIS)

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

    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 137 Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 10 8 or 2 × 10 8 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 × 10 8 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. (author)

  19. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

    2004-01-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131 I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P 131 I-A7 RIT displayed a marked therapeutic effect (n=8) (P 131 I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P 131 I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  20. Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

    Directory of Open Access Journals (Sweden)

    Hourinaz Behesti

    2013-01-01

    BMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers – including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival.

  1. Influence of the combined administration of antibiotic-resistant bifidobacteria and the corresponding antibiotics on the survival of irradiated mice

    International Nuclear Information System (INIS)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal'tsev, V.N.

    1982-01-01

    Mice irradiated with a dose of 700 R were injected with a certain antibiotic (kanamycin, gentamycin, ampicillim and antibiotic resistant bifidobacteria) according to three different schemes. According to the first scheme antibiotic is in ected during the period from 1 to 7-th day, bifidobacteria-on 1, 6, 5, 7, 10, 15, 20 and 25-th day after irradiation, according to the second scheme antibiotic and bifidobacteria were injected from the fifth up to 0-th day after irradiation according to the 3-d scheme antibiotics and bifidobacteria were injected from the first up to 21-st day with 48 h interval. The largest increase in survival rate percent of irradiated animals was observed during combined injection of preparations according to the third scheme. The least medicinal effect was noted during injection of antibiotic and bifidobacteria aceording to the second scheme. Antibiotics and bifidobacteria injected separately increased survival rate of irradiated mice but at a lesser degree as compared with their combined use

  2. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice

    DEFF Research Database (Denmark)

    Lopez-Contreras, Andres J; Specks, Julia; Barlow, Jacqueline H

    2015-01-01

    In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the...

  3. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

    Directory of Open Access Journals (Sweden)

    Takuto Oyama

    2016-06-01

    Full Text Available Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA. MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF and low-biofilm formers (L-BF. These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections.

  4. Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

    Science.gov (United States)

    Summers, Brooke L; Rofe, Allan M; Coyle, Peter

    2009-04-01

    We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

  5. Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

    International Nuclear Information System (INIS)

    Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus

    2014-01-01

    Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves). PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice. Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer

  6. Recombinant M. bovis BCG expressing the PLD protein promotes survival in mice challenged with a C. pseudotuberculosis virulent strain.

    Science.gov (United States)

    Leal, Karen Silva; de Oliveira Silva, Mara Thais; de Fátima Silva Rezende, Andréa; Bezerra, Francisco Silvestre Brilhante; Begnini, Karine; Seixas, Fabiana; Collares, Tiago; Dellagostin, Odir; Portela, Ricardo Wagner; de Carvalho Azevedo, Vasco Ariston; Borsuk, Sibele

    2018-06-14

    The aim of this study was to evaluate the survival of mice inoculated with M. bovis BCG Pasteur recombinant expressing the PLD protein and challenged with a C. pseudotuberculosis virulent strain. Four groups were immunized with a sterile 0.9% saline solution (G1), 10 6  CFU of M. bovis BCG Pasteur (G2), 10 6  CFU of M. bovis BCG/pld (G3) or 10 6  CFU of M. bovis BCG/pld with a booster with rPLD (G4) and challenged with 10 4 CFU of C. pseudotuberculosis MIC-6 strain. The highest survival rate of 88% was observed in G4, followed by 77% in G3 and 66% in G2. A significant statistical difference was observed in the levels of cytokines IFN-γ and IL-10 in vaccinated groups (G3 and G4) when compared with the control group (G1) (p < 0.05). The results seem promising as the recombinant vaccine elicited a cellular immune response and provided significant survival after a high virulent challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721

    International Nuclear Information System (INIS)

    Kinnamon, K.E.; Ketterling, L.L.; Ledney, G.D.; Lorenz, G.B.; Mioduszewski, R.J.; Stampfli, H.F.

    1980-01-01

    For the first time data are presented for animals treated with bone marrow cells after lethal radiation exposure while protected with WR 2721 (the single radioprotective chemical compound with the highest known dose reduction factor). The LD 50 30 (lethal dose to 50% in 30 days) for mice exposed to whole-body 60 Co radiation was elevated from 824 +- 8 rad in unprotected and untreated mice to (a) 1181 +- 33 rad in animals which received syngeneic bone marrow cells after exposure; (b) 1342 +- 27 rad in animals which received WR 2721 before radiation exposure; and (c) 1608 +- 33 rad in animals receiving both the radioprotective agent before exposure and bone marrow engraftment after exposure

  8. Survival and virulence of copper- and chlorine-stressed Yersinia enterocolitica in Experimentally infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; McFeters, G.A.

    1987-08-01

    The effect of gastric pH on the viability and virulence of Yersinia enterocolitica 0:8 after exposure to sublethal concentrations of copper and chlorine was determined in mice. Viability and injury were assessed with a nonselective TLY agar and two selective media, TLYD agar and CIN agar. Both copper and chlorine caused injury which was manifested by the inability of the cells to grow on selective media. CIN agar was more restrictive to the growth of injured cells than TLYD agar. Injury of the exposed cells was further enhanced in the gastric environment of mice. Besides injury, the low gastric pH caused extensive loss of viability in copper-exposed cells. Lethality in the chlorine-exposed cells was less extensive, and a portion of the inoculum reached the small intestine 5 min postinoculation. No adverse effect on the injured cells was apparent in the small intestine, and a substantial revival of the injury occurred in 3 to 4 h after intraluminal inoculation. The virulence of chlorine-stressed Y. enterocolitica in orally inoculated mice was similar to that of the control culture, but copper-stressed cells showed reduced virulence. Virulence was partly restored by oral administration of sodium bicarbonate before the inoculation of copper-exposed cells. Neutralization of gastric acidity had no effect on the virulence of the control of chlorine-stressed cells.

  9. Increased survival of CBA pluripotent haemopoietic stem cells in vitro induced by a marrow stromal factor in Sl/Sl/sup d/ mice

    Energy Technology Data Exchange (ETDEWEB)

    Blackburn, M J; Patt, H M

    1979-07-01

    Media conditioned by marrow adherent cells from anaemic Sl/Sl/sup d/ and W/W/sup v/ mice increased the 24-h survival of CBA CFU/sub s/ in vitro compared to fresh medium to about the same extent as marrow-conditioned medium from normal Sl/sup +//Sl/sup +/, W/sup +//W/sup +/, and CBA mice. Sl/Sl/sup d/ marrow-conditioned medium also increased the percentage of CFU/sub s/ in DNA synthesis to the same extent as CBA marrow-conditioned medium. These results demonstrate that Sl/Sl/sup d/ mice produce a marrow stromal factor that increases both survival of CFU/sub s/ and the percentage of CFU/sub s/ in DNA synthesis in vitro. Therefore, the defective haemopoietic microenvironment of Sl/Sl/sup d/ mice is not due to a deficiency in the production of this factor.

  10. Reduced Self-Diploidization and Improved Survival of Semi-cloned Mice Produced from Androgenetic Haploid Embryonic Stem Cells through Overexpression of Dnmt3b

    Directory of Open Access Journals (Sweden)

    Wenteng He

    2018-02-01

    Full Text Available Summary: Androgenetic haploid embryonic stem cells (AG-haESCs hold great promise for exploring gene functions and generating gene-edited semi-cloned (SC mice. However, the high incidence of self-diploidization and low efficiency of SC mouse production are major obstacles preventing widespread use of these cells. Moreover, although SC mice generation could be greatly improved by knocking out the differentially methylated regions of two imprinted genes, 50% of the SC mice did not survive into adulthood. Here, we found that the genome-wide DNA methylation level in AG-haESCs is extremely low. Subsequently, downregulation of both de novo methyltransferase Dnmt3b and other methylation-related genes was determined to be responsible for DNA hypomethylation. We further demonstrated that ectopic expression of Dnmt3b in AG-haESCs could effectively improve DNA methylation level, and the high incidence of self-diploidization could be markedly rescued. More importantly, the developmental potential of SC embryos was improved, and most SC mice could survive into adulthood. : Ectopic expression of Dnmt3b could rescue DNA methylation level in repetitive sequences of hypomethylated AG-haESCs, suppress high incidence of self-diploidization, and promote developmental potential of SC embryos, and most SC mice could survive into adulthood. Keywords: androgenetic haploid embryonic stem cells, self-diploidization, semi-cloned mice, DNA methylation, Dnmt3b

  11. Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Ehteda, Anahid; Galettis, Peter; Pillai, Krishna; Morris, David L

    2013-01-01

    Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment

  12. Increased haematopoietic stem cell survival in mice injected with tocopherol after X-irradiation

    International Nuclear Information System (INIS)

    Roy, R.M.; Malick, M.A.; Clark, G.M.

    1982-01-01

    Tocopherol injection (2.5 mg) immediately after irradiation reduced lethality only during bone-marrow syndrome. Endogenous spleen colony count at 8 days after X-radiation were significantly greater in vitamin-E-injected mice compared to noninjected or vehicle-injected animals; however, 59 Fe incorporation into spleen and bone marrow did not suggest enhanced erythropoietic activity in vitamin-E-injected groups at 2, 4, 8 and 10 days following irradiation. Mitotic index and frequency of micronuclei in marrow at 24 hours post irradiation (3 GY) were unaffected by tocopherol injection. The uptake of tritium from injected 3 H-tocopherol suggests that tocopherol has been accumulated in spleens but not marrows of irradiated animals within a few hours. Also tocopherol has no effect on endogenous spleen colony counts if injected after 5 hours nor is there an effect on the seeding efficiency of exogenous bonemarrow cells injected into recipients receiving tocopherol after irradiation. (orig.) [de

  13. The dietary polysaccharide maltodextrin promotes Salmonella survival and mucosal colonization in mice.

    Directory of Open Access Journals (Sweden)

    Kourtney P Nickerson

    Full Text Available In the latter half of the 20th century, societal and technological changes led to a shift in the composition of the American diet to include a greater proportion of processed, pre-packaged foods high in fat and carbohydrates, and low in dietary fiber (a "Western diet". Over the same time period, there have been parallel increases in Salmonella gastroenteritis cases and a broad range of chronic inflammatory diseases associated with intestinal dysbiosis. Several polysaccharide food additives are linked to bacterially-driven intestinal inflammation and may contribute to the pathogenic effects of a Western diet. Therefore, we examined the effect of a ubiquitous polysaccharide food additive, maltodextrin (MDX, on clearance of the enteric pathogen Salmonella using both in vitro and in vivo infection models. When examined in vitro, murine bone marrow-derived macrophages exposed to MDX had altered vesicular trafficking, suppressed NAPDH oxidase expression, and reduced recruitment of NADPH oxidase to Salmonella-containing vesicles, which resulted in persistence of Salmonella in enlarged Rab7+ late endosomal vesicles. In vivo, mice consuming MDX-supplemented water had a breakdown of the anti-microbial mucous layer separating gut bacteria from the intestinal epithelium surface. Additionally, oral infection of these mice with Salmonella resulted in increased cecal bacterial loads and enrichment of lamina propria cells harboring large Rab7+ vesicles. These findings indicate that consumption of processed foods containing the polysaccharide MDX contributes to suppression of intestinal anti-microbial defense mechanisms and may be an environmental priming factor for the development of chronic inflammatory disease.

  14. No prolongation of skin allograft survival by immunoproteasome inhibition in mice.

    Science.gov (United States)

    Mundt, Sarah; Basler, Michael; Sawitzki, Birgit; Groettrup, Marcus

    2017-08-01

    The immunoproteasome, a distinct class of proteasomes, which is inducible under inflammatory conditions and constitutively expressed in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Moreover, inhibition of the immunoproteasome subunit LMP7 ameliorates clinical symptoms of autoimmune diseases in vivo and was shown to suppress the development of T helper cell (Th) 1 and Th17 cells and to promote regulatory T-cell (Treg) generation independently of its function in antigen processing. Since Th1 and Th17 cells are detrimental and Treg cells are critical for transplant acceptance, we investigated the influence of the LMP7-selective inhibitor ONX 0914 in a mixed lymphocyte reaction (MLR) in vitro as well as on allograft rejection in a MHC-disparate (C57BL/6 to BALB/c) and a multiple minor histocompatibility antigen (miHA)-disparate (B10.Br to C3H) model of skin transplantation in vivo. Although we observed reduced allo-specific IL-17 production of T cells in vitro, we found that selective inhibition of LMP7 had neither an influence on allograft survival in an MHC-mismatch model nor in a multiple minor mismatch skin transplantation model. We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Culture of normal human blood cells in diffusion chamber systems. I. Granulocyte survival and proliferation. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

    1978-01-01

    Blood cells from four normal volunteers were cultured in diffusion chambers (DC), made of Millipore (MDC) or Nuclepore (NDC) filters, in the peritoneal cavities of whole body X-irradiated (700 rad) mice. The total nucleated cell recovery from the two types of DC over 18 days indicates that the cells in DC persist and proliferate. The mature neutrophilic cells, metamyelocytes (M/sub 5/) + band forms (M/sub 6/) + segmented forms (M/sub 7/), survived with T/sup 1///sub 2/ of 29 and 34 h in MDC and NDC, respectively. The reduction of the cells in the DC was surmised to be due to degeneration and death of the M/sub 7/. The /sup 3/H-diisopropylfluorophosphate (/sup 3/HDFP) labeled M/sub /sub 6/+/sub 7// survival in MDC was slightly shorter than that of unlabeled cells, which may be explained on the basis of the loss of /sup 3/HDFP (5.1%/day) from the cells. The eosinophils survived with an average T/sup 1///sub 2/ of 7.2 days (range 4.8 to 9.6), and the results were comparable in both types of DC. Formation of myeloblasts, promyelocytes, and neutrophilic, eosinophilic and basophilic myelocytes, occasional megakaryocytes and rare normoblasts in DC indicated that the normal human blood contains progenitors (pluripotent and/or committed stem cells) of hemopoietic cells. The neutrophilic cell recovery pattern was similar from both types of DC, but the total number recovered was always greater from NDC than from MDC.

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

    Science.gov (United States)

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

    2017-02-01

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

  17. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P 14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P 14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

  18. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  19. Increase of survival of x-irradiated mice by postirradiation injections of a splenic extract prepared from vaccine or endotoxin-treated syngeneic animals

    Energy Technology Data Exchange (ETDEWEB)

    Tsuneoka, K; Takagi, Y; Shikita, M [National Inst. of Radiological Sciences, Chiba (Japan)

    1977-05-01

    Spleens of mice which had been treated with E. coli endotoxin or typhoid-paratyphoid vaccine were extracted with isotonic saline. The extract was filtered through an asbestos filter and chromatographed on a Sephadex G-200 column. The fraction which was excluded at around 2.5-void volume (molecular weight, about 20,000) was significantly effective in increasing survival of animals when it was repeatedly injected in mice after x irradiation (600 R). The injection caused an increase of the weight of spleen of the animals with an increased number of endogenous spleen colonies. The result suggests that the life-saving effect of the spleen extract is based on its effect of stimulating repopulation of autochthonous hematopoietic cells in the x-irradiated animals. A similar splenic extract prepared from normal mice had an ambiguous effect on the survival of x-irradiated animals.

  20. Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery

    Directory of Open Access Journals (Sweden)

    Sarah E. Sinnett

    2017-06-01

    Full Text Available Intravenous administration of adeno-associated virus serotype 9 (AAV9/hMECP2 has been shown to extend the lifespan of Mecp2−/y mice, but this delivery route induces liver toxicity in wild-type (WT mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM. AAV9/hMECP2 (1 × 1012 viral genomes [vg]; ICM extended Mecp2−/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2−/y mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT. To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends Mecp2−/y survival, without apparent toxicity.

  1. The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

    Science.gov (United States)

    Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

    2013-09-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

  2. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. METHODS: We treated...... mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis...... by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation -- as measured by MRI and by dry/wet weight measurement of water content -- but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage...

  3. Nubp1 is required for lung branching morphogenesis and distal progenitor cell survival in mice.

    Directory of Open Access Journals (Sweden)

    Carsten Schnatwinkel

    Full Text Available The lung is a complex system in biology and medicine alike. Whereas there is a good understanding of the anatomy and histology of the embryonic and adult lung, less is known about the molecular details and the cellular pathways that ultimately orchestrate lung formation and affect its health. From a forward genetic approach to identify novel genes involved in lung formation, we identified a mutated Nubp1 gene, which leads to syndactyly, eye cataract and lung hypoplasia. In the lung, Nubp1 is expressed in progenitor cells of the distal epithelium. Nubp1(m1Nisw mutants show increased apoptosis accompanied by a loss of the distal progenitor markers Sftpc, Sox9 and Foxp2. In addition, Nubp1 mutation disrupts localization of the polarity protein Par3 and the mitosis relevant protein Numb. Using knock-down studies in lung epithelial cells, we also demonstrate a function of Nubp1 in regulating centrosome dynamics and microtubule organization. Together, Nubp1 represents an essential protein for lung progenitor survival by coordinating vital cellular processes including cell polarity and centrosomal dynamics.

  4. Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus: Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

    Directory of Open Access Journals (Sweden)

    Erica R. Glasper

    2018-02-01

    Full Text Available Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus. California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1 biparental care: mate pairs remained with their offspring until weaning; or (2 paternal deprivation (PD: paternal males were permanently removed from their home cage on postnatal day (PND 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile during the forced swim task—an effect that was also not sex

  5. Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

    Science.gov (United States)

    Kutushov, M; Gorelik, O

    2013-01-01

    Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

  6. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Influence of a transfusion of donor leukocytes treated with 8-methoxypsoralen and long-wave ultraviolet light (PUVA) on skin allograft survival in mice

    International Nuclear Information System (INIS)

    Gruner, S.; Noack, F.; Meffert, H.

    1989-01-01

    The influence of pretransplant donor spleen cell infusions on murine skin graft survival was studied. In dependence on the time interval between transplantation and transfusion an accelerated or delayed rejection of the grafts was observed. If the donor spleen cells were treated with the photosensitizer 8-methoxypsoralen and UVA light (PUVA) a graft prolongation was achieved at all time intervals. Furthermore, the survival of antigenically unrelated grafts was also prolonged. An additional immunosuppressive treatment of the recipients with antilymphocyte serum, but not cyclophosphamide, led to a further prolongation of graft survival. The survival of PUVA treated skin grafts was not longer in recipients preinfused with PUVA treated donor cells compared with untreated hosts. The results presented in this work may have implications in clinical organ transplantation to prevent sensitizing reactions by sparing protective mechanisms for the graft. (author)

  8. In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA

    Science.gov (United States)

    Landau, Dustin J; Brooks, Elizabeth Drake; Perez-Pinera, Pablo; Amarasekara, Hiruni; Mefferd, Adam; Li, Songtao; Bird, Andrew; Gersbach, Charles A; Koeberl, Dwight D

    2016-01-01

    Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P Ia, as compared with normal littermates, at 8 months following vector administration (P Ia. PMID:26865405

  9. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  10. Working Longer in Good Health

    NARCIS (Netherlands)

    F.R.M. Leijten (Fenna)

    2015-01-01

    markdownabstractAbstract Due to an ageing society, an increasing retirement age, and high prevalence of chronic health problems among older persons, it is important to understand how older employees [with health problems] can work for longer and productively, often this is termed ‘sustainable

  11. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

    International Nuclear Information System (INIS)

    Longley, R.E.; Good, R.A.

    1986-01-01

    The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras

  12. (+)-Nootkatone and (+)-valencene from rhizomes of Cyperus rotundus increase survival rates in septic mice due to heme oxygenase-1 induction.

    Science.gov (United States)

    Tsoyi, Konstantin; Jang, Hwa Jin; Lee, Young Soo; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Kwak, Jong Hwan; Lee, Dong-Ung; Chang, Ki Churl

    2011-10-11

    The rhizomes of Cyperus rotundus have been used as traditional folk medicine for the treatment of inflammatory diseases. However, the mechanism by which extract of rhizomes of Cyperus rotundus (ECR) elicits anti-inflammation has not been extensively investigated so far. The aim of the present study was to test whether heme oxygenase (HO)-1 induction is involved in the anti-inflammatory action of ECR. Induction of HO-1 and inhibition of inducible nitric oxide synthase (iNOS)/NO production by ECR and its 12 constituents (3 monoterpenes, 5 sesquiterpenes, and 4 aromatic compounds) were investigated using RAW264.7 cells in vitro. In addition, anti-inflammatory action of ECR and its two active ingredients (nookkatone, valencene) were confirmed in sepsis animal model in vivo. ECR increased HO-1 expression in a concentration-dependent manner, which was correlated with significant inhibition of iNOS/NO production in LPS-activated RAW264.7 cells. Among 12 compounds isolated from ECR, mostly sesquiterpenes induced stronger HO-1 expression than monoterpenes in macrophage cells. Nootkatone and valencene (sesquiterpenes) significantly inhibited iNOS expression and NO production in LPS-simulated RAW264.7 cells. Inhibition of iNOS expression by nootkatone, valencene, and ECR were significantly reduced in siHO-1 RNA transfected cells. Furthermore, all three showed marked inhibition of high mobility group box-1 (HMGB1) in LPS-activated macrophages and increased survival rates in cecal ligation and puncture (CLP)-induced sepsis in mice. Taken together, we concluded that possible anti-inflammatory mechanism of ECR is, at least, due to HO-1 induction, in which sesquiterpenes such as nootkatone and valencene play a crucial role. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Predominance of Th1 response, increase of megakaryocytes and Kupffer cells are related to survival in Trypanosoma cruzi infected mice treated with Lycopodium clavatum.

    Science.gov (United States)

    Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Sandri, Patricia Flora; Ferreira, Érika Cristina; Aleixo, Denise Lessa; Pala, Nelson Roberto; de Araújo, Silvana Marques

    2016-12-01

    We investigated the number of megakaryocytes, Kupffer cells and ratios of Th1/Th2 and Th1/Th17 cytokines in survival of mice infected with Y strain of Trypanosoma cruzi and treated with Lycopodium clavatum. In a blind, randomized and controlled assay, Swiss male mice, 8weeks-old, infected with 1400 trypomastigotes (Y strain) were divided into groups and treated with: GLy - Lycopodium clavatum dynamization13c and GCI - alcohol solution 7° GL (vehicle medicine). The treatment was offered two days before infection and on the 2nd, 4th and 6th days after infection, overnight (1mL/100mL) and ad libitum. Parameters assessed were: survival rate, number of megakaryocytes and Kupffer cells, cytokines dosage (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17), Th1/Th2 and Th1/Th17 ratios. The increase in megakaryocytes, Kupffer cells, predominance of Th1 response, with increased TNF-α, IL-10, TNF-α/IL-4, TNF-α/IL-17 and decreased IL-6 IL-6/IL-4, are related to increased survival in mice infected with T. cruzi and treated with Lycopodium clavatum 13c. This result demonstrates the possibility of an alternative approach for the treatment of Chagas disease with dynamized drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

    Directory of Open Access Journals (Sweden)

    Han Jin Cho

    2015-04-01

    Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

  15. Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.

    Science.gov (United States)

    Mihalj, Martina; Kellermayer, Zoltán; Balogh, Peter

    2013-07-01

    Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.

  16. Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors

    Directory of Open Access Journals (Sweden)

    Dabora Sandra L

    2010-02-01

    Full Text Available Abstract Background Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2+/- mice, we compared kidney cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/- mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas associated with TSC, the severity of kidney cystadenomas increases with age in A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but angiogenesis inhibitors (sunitinib and bevacizumab and asparaginase are effective as single agents. However, these drugs are not as effective as rapamycin in that they increased median survival only by 24-27%, while rapamycin increased median survival by 173%. Conclusions Our results indicate that the A/J Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC

  17. High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice

    International Nuclear Information System (INIS)

    Meeran, Syed M.; Singh, Tripti; Nagy, Tim R.; Katiyar, Santosh K.

    2009-01-01

    Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120 mJ/cm 2 ) three times/week for 10 weeks. The mice were then sacrificed and skin and plasma samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. We found that the levels of inflammatory biomarkers were increased in the UVB-exposed skin of the mice fed the high-fat diet than the UVB-exposed skin of the mice fed the control diet. The levels of inflammatory biomarkers of early responses to UVB exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E 2 ), proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser 473 ) were higher in high-fat-diet-fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet than the UVB-irradiated mice fed the control diet, whereas the levels of plasma adiponectin were significantly lower. This pronounced exacerbation of the UVB-induced inflammatory responses in the skin of mice fed a high-fat diet suggests that high-fat diet may increase susceptibility to inflammation-associated skin diseases, including the risk of skin cancer.

  18. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

    Directory of Open Access Journals (Sweden)

    Natalie J Groves

    Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

  19. ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.

    Science.gov (United States)

    Hatakeyama, Shinji; Summermatter, Serge; Jourdain, Marie; Melly, Stefan; Minetti, Giulia C; Lach-Trifilieff, Estelle

    2016-01-01

    Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia. CDD866 was evaluated in association with cisplatin as a standard cytotoxic agent or with everolimus, a molecular-targeted agent against mammalian target of rapamycin (mTOR). In the early studies, the treatment effect on cachexia was investigated, and in the additional studies, the treatment effect on progression of cancer and the associated cachexia was evaluated using body weight loss or tumor volume as interruption criteria. Cisplatin accelerated body weight loss and tended to exacerbate skeletal muscle loss in cachectic animals, likely due to some toxicity of this anti-cancer agent. Administration of CDD866 alone or in combination with cisplatin protected from skeletal muscle weight loss compared to animals receiving only cisplatin, corroborating that ActRII inhibition remains fully efficacious under cisplatin treatment. In contrast, everolimus treatment alone significantly protected the tumor-bearing mice against skeletal muscle weight loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence of everolimus but also showed a non-significant trend for an additive effect on reversing skeletal muscle weight loss. Importantly, both combination therapies slowed down time

  20. Effect of oral administration of lactobacillus acidophilus on the immune responses and survival of BALB/c mice bearing human breast cancer

    Directory of Open Access Journals (Sweden)

    Soltan Dallal MM

    2010-02-01

    an increase in survival rate of this group compared to control mice (p<0.001."n"nConclusion: Results of our study suggested that daily consumption of Lactobacillus acidophilus can regulate immune responses skewed Th1 balance that is needed against tumor, further studies is needed to investigate the other mechanisms of this effect.

  1. FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Seiichiro, E-mail: andosei78102@biscuit.ocn.ne.jp [Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Amano, Hirofumi; Amano, Eri; Minowa, Kentaro; Watanabe, Takashi; Nakano, Soichiro; Nakiri, Yutaka; Morimoto, Shinji; Tokano, Yoshiaki [Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Lin, Qingshun; Hou, Rong; Ohtsuji, Mareki; Tsurui, Hiromichi; Hirose, Sachiko [Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Takasaki, Yoshinari [Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2010-04-09

    FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (S1P) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs. Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis. Among several SLE-prone strains of mice, BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen. In the present study, we examined the effect of FTY720 on lupus nephritis of BXSB mice. FTY720 treatment resulted in a marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen. These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice. Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria. Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration. These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli.

  2. Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

    Science.gov (United States)

    Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

    2015-05-01

    The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

  3. FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice

    International Nuclear Information System (INIS)

    Ando, Seiichiro; Amano, Hirofumi; Amano, Eri; Minowa, Kentaro; Watanabe, Takashi; Nakano, Soichiro; Nakiri, Yutaka; Morimoto, Shinji; Tokano, Yoshiaki; Lin, Qingshun; Hou, Rong; Ohtsuji, Mareki; Tsurui, Hiromichi; Hirose, Sachiko; Takasaki, Yoshinari

    2010-01-01

    FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (S1P) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs. Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis. Among several SLE-prone strains of mice, BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen. In the present study, we examined the effect of FTY720 on lupus nephritis of BXSB mice. FTY720 treatment resulted in a marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen. These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice. Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria. Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration. These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli.

  4. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Directory of Open Access Journals (Sweden)

    Hiba El Hajj

    Full Text Available BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV is the etiologic agent of primary effusion lymphomas (PEL. PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. METHODOLOGY/PRINCIPAL FINDINGS: Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. CONCLUSION/SIGNIFICANCE: These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  5. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Science.gov (United States)

    El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

    2013-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  6. Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.

    1985-01-01

    The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases

  7. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  8. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  9. Intermedin A, a New Labdane Diterpene Isolated from Alpinia intermedia, Prolonged the Survival Time of P-388D1 Tumor-Bearing CDF1 Mice.

    Science.gov (United States)

    Chen, Lih-Geeng; Su, Pei-Jung; Tsai, Po-Wei; Yang, Ling-Ling; Wang, Ching-Chiung

    2017-01-01

    Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n -hexane and aqueous solvents, the n -hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D 1 tumor-bearing CDF1 mice. Two new labdane diterpene derivatives, intermedin A ( 1 ) and intermedin B ( 2 ), and coronarin E ( 3 ) were isolated from the n -hexane layer of A. intermedia . Intermedin A induced apoptosis in HL-60 cells at 30 µg/mL and significantly prolonged the survival time of P-388D 1 tumor-bearing CDF 1 mice by 48.7 % at 20 mg/kg of body weight. We suggest that intermedin A is a major compound of A. intermedia and has a cytotoxic effect on HL-60 and P-388D 1 cells. Georg Thieme Verlag KG Stuttgart · New York.

  10. Development of dark-striped field mice, Apodemus agrarius coreae, as a biological dosimeter in a radio-ecological monitoring system: 2. Survival rates and hematology

    International Nuclear Information System (INIS)

    Kim, Hee Sun; Kim, Chong Soon; Nishmura, Y.

    2005-01-01

    Regarding the management of nuclear power plants and the installation of facilities for radiation waste storage: social concerns over radiation safety are increasing. To understand how environmental radiation affects on human beings, the development of an reasonable monitoring system is required. The existing radio-environmental surveillance systems can be classified into physical and biological monitoring systems. The wild small animals and livestocks were reported to be effective biological indicators of environmental radiation This study investigated the possibility of using dark-striped field mice as a biological dosimetric model to assess the effect of radiation on the human environments. For this study, the criteria for the biological dosimeters of environmental radiation were established as the following: first, it should be an animal from a clear background of species; second, it should inhabit a broad range of areas and in considerable numbers; third, it should maintain identical ecological characteristics; fourth, it should be cohabitating with humans; fifth, it should have been consuming food found in their habitat; and finally, it should indicate a clear doseresponse relationship with high sensitivity. Based on such criteria, this study investigated the possibility of using dark-striped field mice as an effective biological dosimeter. Primarily, their species were classified based on their morphological external characteristics and isoenzymic patterns. The taxonomically classified darkstriped field mice, A. agrarius coreae, were then irradiated to investigate their radiation sensitivity based on the survival rate and hematology in this study

  11. Development of dark-striped field mice, Apodemus agrarius coreae, as a biological dosimeter in a radio-ecological monitoring system: 2. Survival rates and hematology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Sun; Kim, Chong Soon [Korea Hydro and Nuclear Power Co., Ltd., Daejeon (Korea, Republic of); Nishmura, Y. [National Institute of Radiological Sciences, Chiba (Japan)

    2005-07-01

    Regarding the management of nuclear power plants and the installation of facilities for radiation waste storage: social concerns over radiation safety are increasing. To understand how environmental radiation affects on human beings, the development of an reasonable monitoring system is required. The existing radio-environmental surveillance systems can be classified into physical and biological monitoring systems. The wild small animals and livestocks were reported to be effective biological indicators of environmental radiation This study investigated the possibility of using dark-striped field mice as a biological dosimetric model to assess the effect of radiation on the human environments. For this study, the criteria for the biological dosimeters of environmental radiation were established as the following: first, it should be an animal from a clear background of species; second, it should inhabit a broad range of areas and in considerable numbers; third, it should maintain identical ecological characteristics; fourth, it should be cohabitating with humans; fifth, it should have been consuming food found in their habitat; and finally, it should indicate a clear doseresponse relationship with high sensitivity. Based on such criteria, this study investigated the possibility of using dark-striped field mice as an effective biological dosimeter. Primarily, their species were classified based on their morphological external characteristics and isoenzymic patterns. The taxonomically classified darkstriped field mice, A. agrarius coreae, were then irradiated to investigate their radiation sensitivity based on the survival rate and hematology in this study.

  12. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

    International Nuclear Information System (INIS)

    Kramer, M. Gabriela; Masner, Martín; Casales, Erkuden; Moreno, María; Smerdou, Cristian; Chabalgoity, José A.

    2015-01-01

    Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10 8 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10 7 units of an aroC − Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor

  13. The benefits of longer fuel cycle lengths

    International Nuclear Information System (INIS)

    Kesler, D.C.

    1986-01-01

    Longer fuel cycle lengths have been found to increase generation and improve outage management. A study at Duke Power Company has shown that longer fuel cycles offer both increased scheduling flexibility and increased capacity factors

  14. A single dose of an inhibitor of cyclooxygenase 2, meloxicam, administered shortly after irradiation increases survival of lethally irradiated mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Weiterová, Lenka

    2011-01-01

    Roč. 176, č. 2 (2011), s. 269-272 ISSN 0033-7587 R&D Projects: GA ČR(CZ) GA305/08/0158 Grant - others:GA ČR(CZ) GAP303/11/0128 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cyclooxygenase-2 inhibition * lethal irradiation * survival Subject RIV: BO - Biophysics Impact factor: 2.684, year: 2011

  15. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

    Directory of Open Access Journals (Sweden)

    Martha J Harding

    2010-04-01

    Full Text Available Widely accessible small animal models suitable for the study of hepatitis C virus (HCV in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH within a vascularized rat collagen type I/human fibronectin (rCI/hFN gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC in severe combined immunodeficient X beige (SCID/bg mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7 mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM components and/or hepatocyte growth factor (HGF-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  16. SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice.

    Science.gov (United States)

    Qin, Kunhua; Zhang, Ning; Zhang, Zhao; Nipper, Michael; Zhu, Zhenxin; Leighton, Jake; Xu, Kexin; Musi, Nicolas; Wang, Pei

    2018-04-01

    Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-Seq analysis. Reverse transcription-quantitative (RT-q)PCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and active RNA polymerase II were evaluated by chromatin immunoprecipitation. Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin-interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3 lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient mice showed increased sensitivity to streptozotocin. Our results reveal that SIRT6 suppresses Txnip expression in beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability

  17. THE EFFECT OF CAROVERINE AND ITS COMBINATION WITH AMINOOXYACETIC ACID ON SURVIVAL TIME OF MICE WITH EXPERIMENTAL TETANUS

    Directory of Open Access Journals (Sweden)

    Indira Mujezinović

    2013-03-01

    Full Text Available Tetanus is a disease that occurs in humans and various animal species worldwide. Tetanus toxin, after binding itself to nerve structures in the spinal cord, blocking the release of inhibitory transmitors which results in predominance of excitatory transmitors, and this manifestes itself in skeletal muscle spasm. In theory, inhibition of excitatory transmission can try to antagonize a number of ways: by stimulating inhibitory transmission with application inhibitory transmitors, inhibition of excitatory transmission by application of antagonists of excitatory transmitors and combination of antagonists of excitatory transmitors. Bearing this in mind, we attempted to normalize the disorders by tetanus toxin with the use of caroverine, an antagonist of excitatory transmitors, alone and in combination with aminooxyacetic acid (substance that increases the level of GABA. Experiments were conducted on albino mice of both sexes, weight 20-25 g. The experimental tetanus was induced by application of tetanus toxin. The application of caroverine and combination with aminooxyacetic acid was carried out 24 hours after application of tetanus toxin, once per day, until the death. Caroverine, given alone in a dose of 1,2 mg/kg significantly prolonged the LD50 period of mice with experimental tetanus, so the obtained results can be said that its application only at this dose proved to be effective. The combination with aminooxyacetic acid was gave an insignificant extension of mice’s dying time with experimental tetanus in the trial, compared to the control group. Key words: tetanus, tetanus toxin, transmitors, caroverine, aminooxyacetic acid

  18. α-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.

    Science.gov (United States)

    Yao, Yao; Deng, Hai; Li, Pingfei; Zhang, Jian; Zhang, Junbo; Wang, Deping; Li, Songbo; Luo, Yixing; Wei, Zhengping; Bi, Guoyu; Yang, Xiang-Ping; Tang, Zhao-Hui

    2017-03-01

    Sepsis is the leading cause of death among critically ill patients and natural killer T (NKT) cell activation is essential to induce inflammatory cytokine cascade in sepsis. However, little is known about what regulates the NKT cell function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during sepsis. Tim-3 expression was positively correlated with NKT cell activation and apoptosis. In sepsis, interleukin (IL)-12 secreted by dendritic cell exposure to lipopolysaccharide increased the expression of Tim-3 in NKT cells. Administration of α-lactose to block Tim-3 signaling pathway significantly improved the survival of septic mice, concomitant with reduced IL-12 production by dendritic cells, reduced Tim-3 expression, prevented NKT cell apoptosis, and attenuated production of inflammatory cytokines. Collectively, Tim-3 signaling in NKT cells plays a critical role in the immunopathogenesis of sepsis. Thus, α-lactose could be a promising immunomodulatory agent in the treatment of sepsis.

  19. The role of C/EBPa in PD-1+ CD4+ T cells & modulation of RNR activity prolongs survival of mice with AML

    DEFF Research Database (Denmark)

    Norrie, Ida Christine

    of age-dependent PD-1+ CD4+ T cells was therefore investigated as well as its importance for development of PD-1+ CD4+ T cells during leukemic development. My results showed that loss of C/EBPα expression in the lymphoid compartment led to an increased amount of aged PD-1+ CD4+ T cells, but not of young...... PD-1+ CD4+ T cells, suggesting that C/EBPα repress the accumulation of these cells in old mice. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells during development of leukemia. M data indicates......The Ph.D. thesis comprises two projects: (1) C/EBPα is dispensable for the ontogeny of PD1+ CD4+ memory T cells, but restricts their expansion in an age-dependent manner. (2) Modulation of RNR activity prolongs survival of mice with AML. Immunosenescence is a condition of the immune system...

  20. Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

    Science.gov (United States)

    Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T; Xing, Lianping; Hilton, Matthew J; Schwarz, Edward M

    2013-09-01

    The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue-specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project (KOMP) Repository. Tnnt3(lacZ/+) mice are smaller than their WT littermates throughout development but do not display any gross phenotypes. Tnnt3(lacZ/lacZ) embryos are smaller than heterozygotes and die shortly after birth. Histology revealed hemorrhagic tissue in Tnnt3(lacZ/lacZ) liver and kidney, which was not present in Tnnt3(lacZ/+) or WT, but no other gross tissue abnormalities. X-gal staining for Tnnt3 promoter-driven lacZ transgene expression revealed positive staining in skeletal muscle and diaphragm and smooth muscle cells located in the aorta, bladder, and bronchus. Collectively, these findings suggest that troponins are expressed in smooth muscle and are required for normal growth and breathing for postnatal survival. Moreover, future studies with this mouse model can explore TnnT3 function in adult muscle function using the conditional-inducible gene deletion approach Copyright © 2013 Wiley Periodicals, Inc.

  1. Combined intranasal nerve growth factor and ventricle neural stem cell grafts prolong survival and improve disease outcome in amyotrophic lateral sclerosis transgenic mice.

    Science.gov (United States)

    Zhong, Shi-Jiang; Gong, Yan-Hua; Lin, Yan-Chen

    2017-08-24

    Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Nanomedical strategy to prolong survival period, heighten cure rate, and lower systemic toxicity of S180 mice treated with MTX/MIT.

    Science.gov (United States)

    Song, Ning; Zhao, Ming; Wang, Yuji; Hu, Xi; Wu, Jianhui; Jiang, Xueyun; Li, Shan; Cui, Chunying; Peng, Shiqi

    2016-01-01

    In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)-MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN-MTX. The loading of MIT into the surface pores of MSNN-MTX produced nanostructured MSNN-MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN-MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN-MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN-MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively.

  3. Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

    Science.gov (United States)

    Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Ferraz, Fabiana Nabarro; Sandri, Patricia Flora; Hernandes, Luzmarina; Aleixo, Denise Lessa; Barion, Terezinha Fátima; Esper, Luiz Gilson; de Araújo, Silvana Marques

    2017-09-01

    Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The effect of adding fish oil to parenteral nutrition on hepatic mononuclear cell function and survival after intraportal bacterial challenge in mice.

    Science.gov (United States)

    Moriya, Tomoyuki; Fukatsu, Kazuhiko; Maeshima, Yoshinori; Ikezawa, Fumie; Hashiguchi, Yojiro; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

    2012-05-01

    Parenteral nutrition (PN) is indispensable for meeting caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition; however, PN impairs hepatic immunity. We examined the effects of ω-3 and -6 polyunsaturated fatty acids, added individually to fat-free PN, on hepatic immunity in a murine model. We focused on serum liver enzymes, cytokine production, histopathology, and the outcomes after intraportal bacterial challenge. Male Institute of Cancer Research mice were randomized into 4 groups; ad libitum chow (CHOW), fat-free PN (FF-PN), PN + fish oil (FO-PN), or PN + safflower oil (SO-PN). After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. The number of MNCs was counted and cytokine production (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by hepatic MNCs in response to lipopolysaccharide (LPS) was measured. Blood samples were analyzed for hepatobiliary biochemical parameters. Moreover, 1.0 × 10(7) pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined. Hepatic MNC numbers were significantly less in the FO-PN and FF-PN than in the CHOW group, whereas the SO-PN group showed moderate recovery of hepatic MNC numbers. The CHOW, FO-PN, and SO-PN groups showed LPS dose-dependent increases in TNF-α levels. These increases were blunted in the FF-PN group. IL-10 levels were increased LPS dose-dependently in the CHOW and FO-PN groups, but no marked changes were observed with LPS stimulation in the SO-PN and FF-PN groups. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly greater in the FF-PN than in the FO- and SO-PN and CHOW groups. The FO-PN group showed significantly improved survival compared with the SO-PN and FF-PN groups, showing essentially no morphologic hepatic abnormalities. Addition of fish oil to PN was advantageous in terms of reversing PN-induced deterioration of hepatic

  5. Minimum Wage Effects in the Longer Run

    Science.gov (United States)

    Neumark, David; Nizalova, Olena

    2007-01-01

    Exposure to minimum wages at young ages could lead to adverse longer-run effects via decreased labor market experience and tenure, and diminished education and training, while beneficial longer-run effects could arise if minimum wages increase skill acquisition. Evidence suggests that as individuals reach their late 20s, they earn less the longer…

  6. Curcumin longa extract-loaded nanoemulsion improves the survival of endotoxemic mice by inhibiting nitric oxide-dependent HMGB1 release.

    Science.gov (United States)

    Ahn, Min Young; Hwang, Jung Seok; Lee, Su Bi; Ham, Sun Ah; Hur, Jinwoo; Kim, Jun Tae; Seo, Han Geuk

    2017-01-01

    High mobility group box 1 (HMGB1) is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. The murine macrophage RAW264.7 cells were treated with lipopolysaccharide (LPS) and/or a C. longa extract-loaded nanoemulsion (CLEN). The levels of released HMGB1, nitric oxide (NO) production, inducible NO synthase (iNOS) expression, and phosphorylation of mitogen-activated protein kinases were analyzed in RAW264.7 macrophages. The effects of CLEN on survival of endotoxemic model mice, circulating HMGB1 levels, and tissue iNOS expression were also evaluated. We have shown that a nanoemulsion loaded with an extract from the C. longa rhizome regulates cellular inflammatory responses and LPS-induced systemic inflammation by suppressing the release of HMGB1 by macrophages. First, treatment of RAW264.7 macrophages with the nanoemulsion significantly attenuated their LPS-induced release of HMGB1: this effect was mediated by inhibiting c-Jun N-terminal kinase activation, which in turn suppressed the NO production and iNOS expression of the cells. The nanoemulsion did not affect LPS-induced p38 or extracellular signal-regulated kinase activation. Second, intraperitoneal administration of the nanoemulsion improved the survival rate of LPS-injected endotoxemic mice. This associated with marked reductions in circulating HMGB1 levels and tissue iNOS expression. The present study shows for the first time the mechanism by which C. longa ameliorates sepsis, namely, by suppressing NO signaling and thereby inhibiting the release of the proinflammatory cytokine HMGB1. These observations suggest that identification of

  7. Curcumin longa extract-loaded nanoemulsion improves the survival of endotoxemic mice by inhibiting nitric oxide-dependent HMGB1 release

    Directory of Open Access Journals (Sweden)

    Min Young Ahn

    2017-09-01

    Full Text Available Background High mobility group box 1 (HMGB1 is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. Methods The murine macrophage RAW264.7 cells were treated with lipopolysaccharide (LPS and/or a C. longa extract-loaded nanoemulsion (CLEN. The levels of released HMGB1, nitric oxide (NO production, inducible NO synthase (iNOS expression, and phosphorylation of mitogen-activated protein kinases were analyzed in RAW264.7 macrophages. The effects of CLEN on survival of endotoxemic model mice, circulating HMGB1 levels, and tissue iNOS expression were also evaluated. Results We have shown that a nanoemulsion loaded with an extract from the C. longa rhizome regulates cellular inflammatory responses and LPS-induced systemic inflammation by suppressing the release of HMGB1 by macrophages. First, treatment of RAW264.7 macrophages with the nanoemulsion significantly attenuated their LPS-induced release of HMGB1: this effect was mediated by inhibiting c-Jun N-terminal kinase activation, which in turn suppressed the NO production and iNOS expression of the cells. The nanoemulsion did not affect LPS-induced p38 or extracellular signal-regulated kinase activation. Second, intraperitoneal administration of the nanoemulsion improved the survival rate of LPS-injected endotoxemic mice. This associated with marked reductions in circulating HMGB1 levels and tissue iNOS expression. Discussion The present study shows for the first time the mechanism by which C. longa ameliorates sepsis, namely, by suppressing NO signaling and thereby inhibiting the release of the proinflammatory cytokine HMGB1

  8. Bovine lactoferricin induces caspase-independent apoptosis in human B-lymphoma cells and extends the survival of immune-deficient mice bearing B-lymphoma xenografts.

    Science.gov (United States)

    Furlong, Suzanne J; Mader, Jamie S; Hoskin, David W

    2010-06-01

    Although current treatments based on the use of B-cell-specific anti-CD20 monoclonal antibodies and aggressive combinatorial chemotherapy have improved the survival of patients suffering from B-cell non-Hodgkin's lymphoma (NHL), some individuals fail to respond to treatment and relapses remain common. New and more effective treatments for B-cell NHL are therefore required. Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that is cytotoxic for several human tumor cell lines but does not harm healthy cells. Here we show that in vitro treatment with LfcinB caused Raji and Ramos human B-lymphoma cells to die by apoptosis, as indicated by DNA fragmentation, chromatin condensation, and nuclear disintegration. LfcinB killed B-lymphoma cells more efficiently at low serum concentrations and was inhibited in the presence of exogenous bovine serum albumin, suggesting partial neutralization of cationic LfcinB by anionic serum components. LfcinB-induced apoptosis in B-lymphoma cells was caspase-independent since caspase-3 activation was not detected by Western blotting and the general caspase inhibitor z-VAD-fmk did not prevent LfcinB-induced DNA fragmentation. Importantly, immune-deficient SCID/beige mice that were inoculated intravenously with Ramos B-lymphoma cells in order to model B-cell NHL exhibited extended survival following systemic administration of LfcinB, indicating that LfcinB warrants further investigation as a novel therapeutic agent for the possible treatment of B-cell NHL. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Cardiac-specific inducible overexpression of human plasma membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury.

    Science.gov (United States)

    Sadi, Al Muktafi; Afroze, Talat; Siraj, M Ahsan; Momen, Abdul; White-Dzuro, Colin; Zarrin-Khat, Dorrin; Handa, Shivalika; Ban, Kiwon; Kabir, M Golam; Trivieri, Maria G; Gros, Robert; Backx, Peter; Husain, Mansoor

    2018-03-30

    Background: Heart failure (HF) is associated with reduced expression of plasma membrane Ca 2+ -ATPase 4 (PMCA4). Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin. Here we examine temporally regulated cardiac-specific overexpression of hPMCA4b in mouse models of myocardial ischemia reperfusion injury (IRI) ex vivo , and HF following experimental myocardial infarction (MI) in vivo Methods and results: Doxycycline-regulated cardiomyocyte-specific overexpression and activity of hPMCA4b produced adaptive changes in expression levels of Ca 2+ -regulatory genes, and induced hypertrophy without significant differences in Ca 2+ transients or diastolic Ca 2+ concentrations. Total cardiac NOS and nNOS-specific activities were reduced in mice with cardiac overexpression of hPMCA4b while nNOS, eNOS and iNOS protein levels did not differ. hMPCA4b-overexpressing mice also exhibited elevated systolic blood pressure vs. controls, with increased contractility and lusitropy in vivo In isolated hearts undergoing IRI, hPMCA4b overexpression was cardioprotective. NO donor-treated hearts overexpressing hPMCA4b showed reduced LVDP and larger infarct size versus vehicle-treated hearts undergoing IRI, demonstrating that the cardioprotective benefits of hPMCA4b-repressed nNOS are lost by restoring NO availability. Finally, both pre-existing and post-MI induction of hPMCA4b overexpression reduced infarct expansion and improved survival from HF. Conclusions: Cardiac PMCA4b regulates nNOS activity, cardiac mass and contractility, such that PMCA4b overexpression preserves cardiac function following IRI, heightens cardiac performance and limits infarct progression, cardiac hypertrophy and HF, even when induced late post-MI. These data identify PMCA4b as a novel therapeutic target for IRI and HF. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

    Science.gov (United States)

    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.

  11. Influence of metronidazole on the survival rate of whole-body irradiated mice and on the DNA repair synthesis of lymphocytes

    International Nuclear Information System (INIS)

    Magdon, E.; Schroeder, E.

    1978-01-01

    With reference to literature reports the effect of Metronidazole [1-(hydroxyethyl)-5-nitro-2-methyl-imidazole] on the survival rate of C 3 H inbred mice following whole-body doses ranging from 5 to 15 Gy was determined under oxic and hypoxic conditions. Ehrlich ascites tumor cells were used to study the influence of Metronidazole on radiation-induced alterations of the DNA sedimentation behavior in the alkaline sucrose gradient under oxic conditions in vitro. The effect of Metronidazole on the semiconservative DNA synthesis was investigated under oxic and hypoxic conditions in Ehrlich ascites carcinoma cells and L5178Y lymphoma cells. Furthermore, it was examined whether the radiation-induced inhibition of semiconservative DNA synthesis in L5178Y lymphoma cells and the radiation-induced repair synthesis in lymphocytes is influenced by Metronidazole. From the values of the LDsub(50/30) after whole-body irradiation a sensitilization factor of 1.3 was derived for Metronidazole under hypoxic conditions. Under atmospheric conditions an increase of the radiation effect by a factor of 1.1 was obtained. The protective factor of hypoxia was 1.6 and thus greater than the radiosensibilization caused by Metronidazole. The DNA synthesis was slightly inhibited by Metronidazole under both hypoxic and euoxic conditions. The studies revealed no significant influence of Metronidazole on radiation-induced changes of the DNA sedimentation behavior and of the DNA repair synthesis as well as on the radiation induced inhibition of semiconservative DNA synthesis. (author)

  12. Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy.

    Science.gov (United States)

    Park, Jungsun; Li, Haiyan; Zhang, Mingjun; Lu, Yong; Hong, Bangxing; Zheng, Yuhuan; He, Jin; Yang, Jing; Qian, Jianfei; Yi, Qing

    2014-08-01

    Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers.

  13. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Directory of Open Access Journals (Sweden)

    JiangWei Hu

    Full Text Available A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC assay, a hydrogen peroxide (H2O2 content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline that were exposed to 4.5 Gy (60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-CD117(+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01, promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05, reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05, and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0

  14. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Science.gov (United States)

    Hu, JiangWei; Yang, ZaiLiang; Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu

    2013-01-01

    A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, PTrx-1 vs. NS, PTrx-1 vs. hucMSC or NS, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. hucMSC or NS, PTrx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI.

  15. Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice

    International Nuclear Information System (INIS)

    Ikebe, E; Kawaguchi, A; Tezuka, K; Taguchi, S; Hirose, S; Matsumoto, T; Mitsui, T; Senba, K; Nishizono, A; Hori, M; Hasegawa, H; Yamada, Y; Ueno, T; Tanaka, Y; Sawa, H; Hall, W; Minami, Y; Jeang, K T; Ogata, M; Morishita, K; Hasegawa, H; Fujisawa, J; Iha, H

    2013-01-01

    In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression

  16. Protective effect of zinc against lethality of the irradiated mice

    International Nuclear Information System (INIS)

    Matsubara, J.; Inada, T.; Machida, K.

    1982-01-01

    The effects of adding 1000 ppm Zn in the drinking water 10 days before gamma irradiation (562 - 1000 rad) of mice were studied. The mice which had received zinc had a lower mortality rate and a longer survival time compared to the controls. The LD 50 of gamma radiation was 690 rad in the control group and 770 rad in the zinc group. Zinc added to the culture medium of human melanoma cells did not shown any change in radiosensitivity; thus the radioprotective effect of zinc appears to work at the whole body level. (U.K.)

  17. An approach for longer lifetime MCFCs

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Masaru; Tatsumi, Masahiko; Hayano, Takuro [MCFC Research Association, Tokyo (Japan)] [and others

    1996-12-31

    For entering into commercialization of MCFC power plants in the beginning of the 21st century, we will devote to research for increasing lifetime as long as 40,000 hours with cell performance decay rate of 0.25 %/1000hrs as the target in FY 1999. This paper will discuss on our approach for longer lifetime MCFCs through electrolyte-loss management and NiO precipitation management as well as micro-structural control of electrodes and matrix plates. Cell voltage decay rate will be estimated by simulation through series of experiments on accelerated conditions.

  18. Atomic weights: no longer constants of nature

    Science.gov (United States)

    Coplen, Tyler B.; Holden, Norman E.

    2011-01-01

    Many of us were taught that the standard atomic weights we found in the back of our chemistry textbooks or on the Periodic Table of the Chemical Elements hanging on the wall of our chemistry classroom are constants of nature. This was common knowledge for more than a century and a half, but not anymore. The following text explains how advances in chemical instrumentation and isotopic analysis have changed the way we view atomic weights and why they are no longer constants of nature

  19. Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice. Increased small intestinal crypt survival, crypt lengths and prolongation of average time to death

    International Nuclear Information System (INIS)

    Ohara, Masayuki; Lu, Huimei; Shiraki, Katsutomo; Ishimura, Yoshimasa; Uesaka, Toshihiro; Katoh, Osamu; Watanabe, Hiromitsu

    2001-01-01

    The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60 Co-γ-ray irradiation at a dose rate of 2 Gy min -1 . Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min -1 , the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects. (author)

  20. Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and prolongation of average time to death.

    Science.gov (United States)

    Ohara, M; Lu, H; Shiraki, K; Ishimura, Y; Uesaka, T; Katoh, O; Watanabe, H

    2001-12-01

    The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects.

  1. Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.

    Science.gov (United States)

    Kim, Tae S; Jung, Mi Y; Cho, Daeho; Cohen, Edward P

    2006-10-30

    Breast cancer cells, like other types of neoplastic cells, form weakly immunogenic tumor-associated antigens. The antigenic properties of the tumor-associated antigens can be enhanced if they are expressed by highly immunogenic cells. In this study, a cancer vaccine was prepared by transfer of a cDNA expression library from SB5b breast carcinoma into mouse fibroblast cells of C3H/He mouse origin (H-2(k)), that had been previously modified to secrete GM-CSF and to express allogeneic class I-determinants (H-2(b)). The transfected syngeneic/allogeneic fibroblasts secreting GM-CSF were used as a vaccine in C3H/He mice. Robust cell-mediated immunity toward the breast cancer cells was generated in mice immunized with the cDNA-based vaccine. The immunity, mediated predominantly by CD8(+) T lymphocytes, was directed toward the breast cancer cells, but not against either of two other non-cross-reactive neoplasms of C3H/He mice. The immunity was sufficient to prolong the survival of mice with established breast cancer. Among other advantages, preparation of the vaccine by cDNA-transfer into a fibroblast cell line enabled the recipient cells to be modified in advance of DNA-transfer to augment their immunogenic properties. As the transferred DNA is replicated as the transfected cells divide, the vaccine could be prepared from microgram quantities of tumor tissue.

  2. LASP-06: Drug Efficacy in a Three-Arm Survival Study in Kras/p53 Pancreatic Ductal Adenocarcinoma (PDAC) Mice | FNLCR

    Science.gov (United States)

    The Laboratory Animal Sciences Program will induce breed 50 KPC animals with the intent of generating a cohort of 40 animals with confirmed tumor-load matching the following enrollment criteria:female mice are considered eligible for enrollment

  3. Purple sweet potato color alleviates D-galactose-induced brain aging in old mice by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C-mediated apoptosis.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Zhang, Zi-feng

    2010-05-01

    Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which might be attributed to its antioxidant property. PSPC also suppressed the activation of c-Jun NH(2)-terminal kinase (JNK) and the release of cytochrome c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal-treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase (PI3K) activation was required for PSPC to promote the neuronal survival accompanied with phosphorylation and activation of Akt and p44/42 mitogen-activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism. The present results suggest that neuronal survival promoted by PSPC may be a potentially effective method to enhance resistance of neurons to age-related disease.

  4. Women live longer than men even during severe famines and epidemics

    DEFF Research Database (Denmark)

    Zarulli, Virginia; Barthold Jones, Julia A; Oksuzyan, Anna

    2018-01-01

    Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We...... investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men...

  5. Live Longer, Work Longer: Making It Happen in the Labor Market

    Directory of Open Access Journals (Sweden)

    Milan Vodopivec

    2008-03-01

    Full Text Available An aging population and the corresponding shrinkage of the labor force will create a significant drag on economic growth and may jeopardize the economic well-being of some of the elderly. Thus working longer is an imperative – but extending working lives has proven difficult, both because workers do not want to work longer and because employers are lukewarm about employing older workers. As measures that can be taken to motivate workers to work longer, the paper proposes providing retirement incentives and attractive, flexible working arrangements. To induce employers to hire old workers, it suggests removing the obstacles imposed by restrictive labor market institutions, an increase in the human capital of workers via life-long learning, and addressing age-discrimination. Chances for extending working lives will also increase as the health of elderly workers is improved.

  6. Radioprotective effect of colony-stimulating factor on mice irradiated with 60Co γ-rays

    International Nuclear Information System (INIS)

    Zhang Junning; Wang Tao; Xu Changshao; Wang Hongyun

    1995-01-01

    Adult male mice were irradiated with γ-rays 6 Gy once or 3 Gy three times in 7 days and intraperitoneally injected with colony-stimulating factor (CSF) in high doses or low doses. Mice of the control group were injected with normal saline only. Within 30 days after irradiation, the survival rate of mice irradiated with 6 Gy γ-rays once and treated with high dose CSF was 9/25, while that in the control group was 2/25. The survival rate of mice irradiated with 3 Gy three times and treated with high dose CSF was 10/13, while that in the control group was 4/13. Moreover, the survival times of both irradiated groups treated with high dose CSF were much longer than the control groups (p<0.01). This experiment also showed that CSF could reduce the lowering of peripheral blood white blood cell counts and promote their recovery. The number of CFU-S in mice treated with CSF was much higher (23.8 +- 4.82) than in the control group (9.4 +- 4.39) (p<0.01). Therefore, CSF could recover and reconstruct the hematopoietic function of bone marrow, and prolong the survival of irradiated mice

  7. Toxoplasma gondii-derived synthetic peptides containing B- and T-cell epitopes from GRA2 protein are able to enhance mice survival in a model of experimental toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Luciana Machado Bastos

    2016-06-01

    Full Text Available Toxoplasmosis is a zoonosis distributed all over the world, which the etiologic agent is an intracellular protozoan parasite, Toxoplasma gondii. This disease may cause abortions and severe diseases in many warm-blood hosts, including humans, particularly the immunocompromised patients. The parasite specialized secretory organelles, as micronemes, rhoptries and dense granules, are critical for the successful parasitism. The dense granule protein 2 (GRA2 is a parasite immunogenic protein secreted during infections and previous studies have been shown that this parasite component is crucial for the formation of intravacuolar membranous nanotubular network (MNN, as well as for secretion into the vacuole and spatial organization of the parasites within the vacuole. In the present study, we produced a monoclonal antibody to GRA2 (C3C5 mAb, isotype IgG2b, mapped the immunodominant epitope of the protein by phage display and built GRA2 synthetic epitopes to evaluate their ability to protect mice in a model of experimental infection. Our results showed that synthetic peptides for B- and T-cell epitopes are able to improve survival of immunized animals. In contrast with non-immunized animals, the immunized mice with both B- and T-cell epitopes had a better balance of cytokines and demonstrated higher levels of IL-10, IL-4 and IL-17 production, though similar levels of TNF-alpha and IL-6 were observed. The immunization with both B- and T-cell epitopes resulted in survival rate higher than 85% of the challenged mice. Overall, these results demonstrate that immunization with synthetic epitopes for both B- and T-cells from GRA2 protein can be more effective to protect against infection by T. gondii.

  8. Experimental transmission of M. leprae into the testes of mice born from 60Co-irradiated pregnant mice

    International Nuclear Information System (INIS)

    Sushida, Kiyo; Tanemura, Mutsuko

    1979-01-01

    R 1 -mice, which were born from pregnant mice (R-P) irradiated with 60 CO 300 R were inoculated with leprosy bacilli into the testis. Recently, the author reported that the skin homograft survival duration in 60 CO-irradiated mice (R-P) was shown to be longer than the duration in the R 1 -F mice. The acid-fast bacilli, the so-called globi, were often found at the inoculated site of R-P mice, but not in the R 1 -F mice. The R 1 -F females bred with normal males and the R 2 -F females bred with normal males were both irradiated with 60 CO 300 R, and the R 2 -F male offspring from this R 1 -F and the R 3 -F male offspring from this R 2 -F showed the same increase in sensitivity to leprosy bacilli as the R-P generation. Acid-fast bacilli (globi, +G) were also found in the testes of the R 2 -F and R 3 -F males. IR-F mice which had received 131 I-Na 100 μci injections and also 60 CO 300 R irradiations during their fetus-term, showed few increase in sensitivity to infection of leprosy bacilli. (author)

  9. Radiation carcinogenesis in radiosensitive mutant Scid mice

    International Nuclear Information System (INIS)

    Ogiu, Toshiaki; Ishii-Ohba, Hiroko; Kobayashi, Shigeru; Nishimura, Mayumi; Shimada, Yoshiya; Tsuji, Hideo; Watanabe, Fumiaki; Suzuki, Fumio; Sado, Toshihiko

    2000-01-01

    The Scid mice were established as a severe combined immunodeficient mouse strain lacking both T- and B-cell functions. Scid (homozygote), its parent strain C.B-17 (wild-type) and their hybrid F1 (heterozygote) were used for analysis of the relationship between sensitivity to acute effects of ionizing radiation and radiation-tumor development. Acute effects were studied using γ-rays and LD 50(30) was found to be 4.05 Gy in Scid, 6.5 Gy in F1 and 7.2 Gy in C.B-17. When bone marrow cells were irradiated with X-rays in vitro, survival curves of C.B-17 and F1 cells showed a region of shoulder with D 0 =0.68 and 0.67 Gy, respectively, while those of Scid were of no shoulder with D 0 =0.46 Gy. Scid mice died due to tumors (most were thymic lymphoma, T/L) 20-40 weeks after irradiation with 1-3 Gy γ-rays but C.B-17 and F1 survived longer. Bone marrow transplantation was found effective to prevent the radiation T/L. FACS analysis for surface antigens of those T/L cells suggested the change of Ras oncogenes. The change of Notch 1 gene was suggested by Southern hybridization and thus a possible role of defective DNA-PK in mice alone (not in rats and humans) was suggested as well. (K.H.)

  10. Women live longer than men even during severe famines and epidemics.

    Science.gov (United States)

    Zarulli, Virginia; Barthold Jones, Julia A; Oksuzyan, Anna; Lindahl-Jacobsen, Rune; Christensen, Kaare; Vaupel, James W

    2018-01-23

    Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors. Copyright © 2018 the Author(s). Published by PNAS.

  11. Women live longer than men even during severe famines and epidemics

    Science.gov (United States)

    Zarulli, Virginia; Barthold Jones, Julia A.; Oksuzyan, Anna; Lindahl-Jacobsen, Rune; Christensen, Kaare; Vaupel, James W.

    2018-01-01

    Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors. PMID:29311321

  12. Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2017-04-01

    Full Text Available Summary: Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC function. Latexin (Lxn is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1 was a potential downstream target with a dramatic downregulation in Lxn-null HSCs. Enforced expression of Thbs1 restored the Lxn inactivation-mediated HSC phenotypes. This study reveals that Lxn plays an important role in the maintenance of homeostatic hematopoiesis, and it may lead to development of safe and effective approaches to manipulate HSCs for clinical benefit. : In this article, Liang and colleagues show that loss of latexin in vivo expands the HSC population and increases their survival and engraftment. Latexin regulates HSC function and hematopoiesis via the Thbs1 signaling pathway. Keywords: latexin, hematopoietic stem cell, repopulating advantage, expansion, survival, thrombospondin 1

  13. Response of the RIF-1 tumor in vitro and in C3H/Km mice to x-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages

    International Nuclear Information System (INIS)

    Brown, J.M.; Twentyman, P.R.; Zamvil, S.S.

    1980-01-01

    The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D 0 values of 110 and 133 rads and extrapolation numbs of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide

  14. Relative expression of bacterial and host specific genes associated with probiotic survival and viability in the mice gut fed with Lactobacillus plantarum Lp91.

    Science.gov (United States)

    Chandran, Archana; Duary, Raj Kumar; Grover, Sunita; Batish, Virender Kumar

    2013-11-07

    The present investigation was aimed at studying the relative expression of atpD (a key part of F1F0-ATPase operon), bsh (bile salt hydrolase), mub (mucus-binding protein) and MUC2 (mucin) genes in mouse model for establishing the in vivo functional efficacy of Lactobacillus plantarum Lp91 (MTCC5690) by reverse transcription-quantitative PCR (RT-qPCR). The atpD gene was significantly up-regulated to 2.0, 2.4 and 3.2 folds in Lp91 after 15, 30 and 60 min transit in the stomach of mice. The maximal significant (Pstrain Lp5276 after seven days of mice feeding. Simultaneously, mub gene expression increased to 12.8 and 22.7 fold in both Lp91 and Lp5276, respectively. The expression level of MUC2 was at the level of 1.6 and 2.1 fold in the host colon on administration with Lp91 and Lp5276 feeding, respectively. Hence, the expression of atpD, bsh, mub, MUC2 could be considered as prospective and potential biomarkers for screening of novel probiotic lactobacillus strains for optimal functionality in the gut. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    John F. Hernández

    Full Text Available Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

  16. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  17. Effects of gamma irradiation on the survival and development of Gymnophalloides seoi in C3H mice. Final report for the period 1 November 1994 - 31 October 1995

    International Nuclear Information System (INIS)

    Chai Yong-Vil

    1996-01-01

    Gymnophalloides seoi is a peculiar human intestinal trematode in Korea transmitted by oysters. This study was carried out to observe the effects of radiation on the infectivity of G. seoi metacercariae to C3H mice and to assess the applicability of radiation for use in the control of gymnophalloidiasis. Oysters were collected from the endemic area. Non-irradiated control, metacercaria-irradiation, and oyster-irradiation groups were prepared. One hundred metacercariae were infected orally to each mouse, and worm recovery rates of three groups were compared at the seventh day post-infection. In the metacercaria-irradiation group, the worm recovery rate was significantly reduced at radiation doses higher than 200 Gy, and the number of intrauterine eggs was significantly reduced at doses over 50 Gy. In the oyster-irradiation group, 50 Gy significantly reduced the worm recovery rate and number of uterine eggs. In the two groups, no worm was recovered at 1,000 Gy. In conclusion, G. seoi metacercariae showed some resistance to radiation at lower doses than 200 Gy, but irradiation of oyster with 200-1,000 Gy could be applied as a control measure for gymnophalloidiasis. (author). 10 refs, 3 figs, 2 tabs

  18. One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletons.

    Science.gov (United States)

    Gerbaix, Maude; Gnyubkin, Vasily; Farlay, Delphine; Olivier, Cécile; Ammann, Patrick; Courbon, Guillaume; Laroche, Norbert; Genthial, Rachel; Follet, Hélène; Peyrin, Françoise; Shenkman, Boris; Gauquelin-Koch, Guillemette; Vico, Laurence

    2017-06-01

    The weightless environment during spaceflight induces site-specific bone loss. The 30-day Bion-M1 mission offered a unique opportunity to characterize the skeletal changes after spaceflight and an 8-day recovery period in mature male C57/BL6 mice. In the femur metaphysis, spaceflight decreased the trabecular bone volume (-64% vs. Habitat Control), dramatically increased the bone resorption (+140% vs. Habitat Control) and induced marrow adiposity invasion. At the diaphysis, cortical thinning associated with periosteal resorption was observed. In the Flight animal group, the osteocyte lacunae displayed a reduced volume and a more spherical shape (synchrotron radiation analyses), and empty lacunae were highly increased (+344% vs. Habitat Control). Tissue-level mechanical cortical properties (i.e., hardness and modulus) were locally decreased by spaceflight, whereas the mineral characteristics and collagen maturity were unaffected. In the vertebrae, spaceflight decreased the overall bone volume and altered the modulus in the periphery of the trabecular struts. Despite normalized osteoclastic activity and an increased osteoblast number, bone recovery was not observed 8 days after landing. In conclusion, spaceflight induces osteocyte death, which may trigger bone resorption and result in bone mass and microstructural deterioration. Moreover, osteocyte cell death, lacunae mineralization and fatty marrow, which are hallmarks of ageing, may impede tissue maintenance and repair.

  19. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  20. TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice.

    Science.gov (United States)

    Zago, María Paola; Hosakote, Yashoda M; Koo, Sue-Jie; Dhiman, Monisha; Piñeyro, María Dolores; Parodi-Talice, Adriana; Basombrio, Miguel A; Robello, Carlos; Garg, Nisha J

    2016-06-01

    Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (≥2-fold change, P < 0.05), showed that several proteins involved in (i) cytoskeletal assembly and remodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specific antioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhanced protein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxide dismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant to exogenous treatment with stable oxidants (H2O2 and peroxynitrite [ONOO(-)]) and dampened the intracellular superoxide and nitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expression conducive to increase in motility and control of macrophage-derived free radicals provides survival and persistence benefits to TcI isolates of T. cruzi. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Joo [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Seoul National University Bundang Hospital, Seoul (Korea, Republic of); Lee, Eun Kyung [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Lee, Yoon Kwang [Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Park, Do Joon; Jang, Hak Chul [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Moore, David D., E-mail: moore@bcm.edu [Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States)

    2012-09-01

    Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR{sup −/−} mice, but not in hypothyroid PXR{sup −/−} mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR{sup −/−} hypothyroid mice, and this induction was abolished in CAR{sup −/−} mice and in and CAR{sup −/−} PXR{sup −/−} double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR{sup −/−} mice and lowest in WT and PXR{sup −/−} mice. Hypothyroid WT or PXR{sup −/−} mice survived chronic CBZ treatment, but all hypothyroid CAR{sup −/−} and CAR{sup −/−} PXR{sup −/−} mice died, with CAR{sup −/−}PXR{sup −/−} mice surviving longer than CAR{sup −/−} mice (12.3 ± 3.3 days vs. 6.3 ± 2.1 days, p = 0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge. -- Highlights: ► Hypothyroid status activates CAR in mice and induces Cyp2b10 expression. ► Hypothyroid status suppresses PXR activity in mice and represses Cyp3a11 expression. ► These responses balance each other out in normal mice.

  2. Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice

    International Nuclear Information System (INIS)

    Park, Young Joo; Lee, Eun Kyung; Lee, Yoon Kwang; Park, Do Joon; Jang, Hak Chul; Moore, David D.

    2012-01-01

    Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR −/− mice, but not in hypothyroid PXR −/− mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR −/− hypothyroid mice, and this induction was abolished in CAR −/− mice and in and CAR −/− PXR −/− double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR −/− mice and lowest in WT and PXR −/− mice. Hypothyroid WT or PXR −/− mice survived chronic CBZ treatment, but all hypothyroid CAR −/− and CAR −/− PXR −/− mice died, with CAR −/− PXR −/− mice surviving longer than CAR −/− mice (12.3 ± 3.3 days vs. 6.3 ± 2.1 days, p = 0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge. -- Highlights: ► Hypothyroid status activates CAR in mice and induces Cyp2b10 expression. ► Hypothyroid status suppresses PXR activity in mice and represses Cyp3a11 expression. ► These responses balance each other out in normal mice. ► Hypothyroidism sensitizes CAR null mice to toxic effects of carbamazepine.

  3. IPO survival in a reputational market

    OpenAIRE

    Espenlaub, Susanne; Khurshed, Arif; Mohamed, Abdulkadir

    2012-01-01

    We examine IPO survival in a 'reputational' market, the Alternative Investment Market (AIM), where principle-based regulation pivots on the role of a regulatory agent, the nominated advisor (Nomad) to the IPO company. We find that Nomad reputation has a significant impact on IPO survival. IPOs backed by reputable Nomads 'survive longer (by about two years) than those backed by other Nomads. We also find that survival rates of AIM IPOs are broadly comparable to those of North American IPOs. Wh...

  4. Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice.

    Science.gov (United States)

    Tabari, M Abouhosseini; Ebrahimpour, S

    2014-01-01

    Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.

  5. IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154–CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice

    Directory of Open Access Journals (Sweden)

    Dela Golshayan

    2017-04-01

    Full Text Available In recent years, regulatory T cells (Treg-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT. However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells. IL-2-mediated Treg expansion in combination with short-term CD154–CD40 co-stimulation blockade, but not CTLA-4 Ig or rapamycin, led to tolerance to MHC-mismatched skin grafts in non-lymphopenic mice, mainly by hindering alloreactive CD8+ effector T cells and the production of alloantibodies. Importantly, this treatment also allowed prolonged survival of allografts in the presence of either donor-specific or cross-reactive memory cells. However, late rejection occurred in sensitized hosts, partly mediated by activated B cells. Overall, these data illustrate the potential but also some important limitations of Treg-based therapy in clinical SOT as well as the importance of concomitant immunomodulatory strategies in particular in sensitized hosts.

  6. Impact on environmental qualification from a longer fuel cycle

    International Nuclear Information System (INIS)

    Sanwarwalla, M.H.; Akhtar, S.; Drankhan, D.A.

    1996-01-01

    There is a general trend in the nuclear industry towards longer fuel cycles because of the economic benefits. The economic benefits for increasing the fuel cycle from eighteen to twenty four months is estimated by the industry to be about $5.05 million per unit year based on a two week mid-cycle maintenance outage. Equipment with a unique characteristic may require maintenance and/or inspection more frequently than can be accommodated in a longer cycle. The maintenance and surveillance (M ampersand S) requirements for these equipment need to be reviewed to accommodate a longer cycle and avoid any unplanned outage. ComEd's LaSalle Station is considering a move to a longer fuel cycle. A study was done to determine the impact of a longer fuel cycle on their current environmental qualification (EQ) program, and the feasibility of implementing changes to their program to accommodate a longer fuel cycle. This paper discusses (1) the impact, if any, the longer fuel cycle will have on the maintenance and surveillance requirements of the 50.49 or environmentally qualified equipment at LaSalle Station, (2) the various techniques, i.e., partial testing, performance based monitoring etc., employed to extend the existing maintenance and surveillance requirements, and (3) the estimated economic savings, if any, from the extended M ampersand S interval

  7. Protocol for Short- and Longer-term Spatial Learning and Memory in Mice

    Directory of Open Access Journals (Sweden)

    Emily F. Willis

    2017-10-01

    Full Text Available Studies on the role of the hippocampus in higher cognitive functions such as spatial learning and memory in rodents are reliant upon robust and objective behavioral tests. This protocol describes one such test—the active place avoidance (APA task. This behavioral task involves the mouse continuously integrating visual cues to orientate itself within a rotating arena in order to actively avoid a shock zone, the location of which remains constant relative to the room. This protocol details the step-by-step procedures for a novel paradigm of the hippocampal-dependent APA task, measuring acquisition of spatial learning during a single 20-min trial (i.e., short-term memory, with spatial memory encoding and retrieval (i.e., long-term memory assessed by trials conducted over consecutive days. Using the APA task, cognitive flexibility can be assessed using the reversal learning paradigm, as this increases the cognitive load required for efficient performance in the task. In addition to a detailed experimental protocol, this paper also describes the range of its possible applications, the expected key results, as well as the analytical methods to assess the data, and the pitfalls/troubleshooting measures. The protocol described herein is highly robust and produces replicable results, thus presenting an important paradigm that enables the assessment of subtle short-term changes in spatial learning and memory, such as those observed for many experimental interventions.

  8. Education and Training: Is There Any Longer a Useful Distinction?

    Science.gov (United States)

    Hager, Paul; Laurent, John

    1990-01-01

    Although education and training were distinct concepts when Taylorism dominated the workplace, it is no longer appropriate to separate them. Today's highly competitive environment requires the education of a flexible, multiskilled workforce, not training for narrowly defined employment tasks. (SK)

  9. The economic efficiency of allowing longer combination vehicles in Texas.

    Science.gov (United States)

    2011-08-01

    This paper shows the economic efficiency of allowing longer combination vehicles in Texas. First, an : overview of the truck size and weight policies is explained, with an emphasis on those that affect : Texas. Next, LCV operations in other countries...

  10. Survival of adult neurons lacking cholesterol synthesis in vivo.

    Science.gov (United States)

    Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

    2007-01-02

    Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  11. Survival of adult neurons lacking cholesterol synthesis in vivo

    Directory of Open Access Journals (Sweden)

    Möbius Wiebke

    2007-01-01

    Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  12. Effect of longer health service provider delays on stage at diagnosis and mortality in symptomatic breast cancer.

    Science.gov (United States)

    Murchie, P; Raja, E A; Lee, A J; Brewster, D H; Campbell, N C; Gray, N M; Ritchie, L D; Robertson, R; Samuel, L

    2015-06-01

    This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer. Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors. Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality. Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. [Effects of the Chinese herbal extract Songyou Yin on the residual hepatocellular carcinoma after chemotherapy in nude mice].

    Science.gov (United States)

    Xiong, Wei; Tang, Zhao-you; Ren, Zheng-gang; Huang, Xiu-yan; Jia, Qing-an; Xie, Xiao-ying; Shen, Hu-jia

    2013-11-01

    To investigate the effects of a Chinese herbal extract Songyou Yin on residual hepatocellular carcinoma after chemotherapy in nude mice and the relevant mechanisms. Orthotopic nude mouse models bearing residual hepatocellular carcinoma after chemotherapy was established using human liver carcinoma MHCC97L cells. Three different doses of Songyon Yin (2.1 g/kg, 4.2 g/kg and 8.4 g/kg) were administered to the mice in the trial groups by intragastric gavage, respectively. The mice in the control group were administered physiological saline. The tumor growth, metastasis and survival in the mice of each group were recorded. The corresponding mechanisms were studied. The pulmonary metastasis rates of the control group and 2.1g/kg, 4.2g/kg, 8.4g/kg Songyou Yin treatment group were 86.7%, 73.3%, 40.0%, and 20.0%, respectively, and the survivals of these groups were 53.83 ± 4.71, 56.50 ± 6.09, 66.67 ± 5.61, 81.17 ± 7.36 days, respectively. Compared with the mice in the control group, mice in the 4.2 g/kg, 8.4 g/kg Songyou Yin treatment groups had a lower pulmonary metastasis rate (P = 0.021 and P = 0.001, respectively) and longer survival (P = 0.002 and P = 0.001, respectively). A restoration of E-cadherin expression and a concomitant reduction of N-cadherin expression were detected in the tumors of the 4.2 g/kg and 8.4 g/kg Songyou Yin treatment groups. Songyou Yin effectively inhibits the invasion and metastasis of the residual hepatocellular carcinoma after chemotherapy in nude mice through attenuating the epithelia-mesenchymal transition and prolongs the survival. Songyon Yin may have potential to promote the efficacy of chemotherapy in hepatocellular carcinoma.

  14. Effects of low-dose rate irradiation on two types of type II diabetes model mice

    International Nuclear Information System (INIS)

    Nomura, Takaji; Sakai, Kazuo

    2004-01-01

    The effects of low-dose rate gamma-irradiation were investigated in two mouse strains - C57BL/KsJ-db/db (db mouse) and AKITA (AKITA mouse)-for type II diabetes mellitus. Both strains develop the developed type II diabetes by about 8 weeks of age due to dysfunction of the insulin/insulin receptor. The db Mouse' shows obese and exhibits hyperinsulinism, and the onset of Type II diabetes like resembles that for Westerners. On the other hand, the AKITA mouse has exhibits disordered insulin secretion, and the diabetes such as resembles that of Asians. Ten-week old female mice, in groups of 8 or 12, were irradiated at 0.65 mGy/hr in the low-dose rate irradiation facility in the Low Dose Radiation Research Center. The level of urine glucose was measured with test slips. The urine glucose levels of all of the mice were highly elevated the beginning of the irradiation. In the irradiated group of db mice, three mice showed decrease in glucose level compare to the level of non-irradiated diabetes mice after 35, 52 or 80 weeks of irradiation. All had maintained a normal level thereafter. No such improvement in diabetes was ever observed in the 12 mice of in the non-irradiated control group. The AKITA mice, however, did not decrease the glucose level regardless of the irradiation. Both the db mice and AKITA mice had their lives prolonged their life by the irradiation. The survival rate of db mice at the age of 90 weeks was 75% in the irradiated group, but 50% in the non-irradiated group. The average life span was 104 weeks in the irradiated group and 87 weeks in the control group. Furthermore, a marked difference was furthermore observed in the appearance of the coat hair, skin, and tail; appearances were well preserved in the irradiated group. The average life span in the irradiated AKITA mice was also longer than that for the non-irradiated mice, 51 weeks and 41 weeks in the irradiated and non-irradiated group respectively. These results suggest that the low-dose irradiation

  15. Working longer in good health [Langer doorwerken in goede gezondheid

    NARCIS (Netherlands)

    Leijten, F.R.M

    2015-01-01

    Due to an ageing society, an increasing retirement age, and high prevalence of chronic health problems among older persons, it is important to understand how older employees [with health problems] can work for longer and productively, often this is termed ‘sustainable employability’. This context

  16. The longer term experiences of parent training: a qualitative analysis.

    Science.gov (United States)

    Furlong, M; McGilloway, S

    2015-09-01

    Child conduct problems are a major public health priority. Group-based parenting programmes are popular in addressing such problems, but evidence for their longer-term effectiveness is limited. Moreover, process evaluations are rare and little is understood about the key facilitative and inhibitive factors associated with maintaining outcomes in the longer term. This study involved the use of qualitative methods as part of a larger process evaluation to explore the longer-term experiences of parents who participated in a randomized controlled trial (RCT) of the Incredible Years Parenting Programme (IYPP) in disadvantaged settings in Ireland. A series of one-to-one in-depth interviews was conducted with parents at 12- (n = 20) and 18-month follow-up (n = 8) and analysed using constructivist grounded theory. Most parents reported positive child behaviour despite several challenges, but a substantial subset reported periods of relapse in positive outcomes. A relapse in child behaviour was linked to relinquishing skills in stressful times, the negative influence of an unsupportive environment, and the perceived ineffectiveness of parenting skills. Resilience in implementing skills despite adversity, and the utilization of available social supports, were associated with the maintenance of positive outcomes. Strengthening resilience and social support capacities may be important factors in maintaining positive longer-term outcomes. Those who design, research and deliver parenting programmes might consider the possibility of including a relapse-prevention module and/or the provision of post-intervention supports for more vulnerable families. © 2014 John Wiley & Sons Ltd.

  17. Revisiting Academic Capitalism in Canada: No Longer the Exception

    Science.gov (United States)

    Metcalfe, Amy Scott

    2010-01-01

    In "Academic Capitalism: Politics, Policies, and the Entrepreneurial University" (1997), Slaughter and Leslie found that Canada showed signs of resisting academic capitalism. Changes in postsecondary education funding policies and the emergence of new commercialization initiatives are evidence that Canada is certainly no longer, and…

  18. Longer rest periods for intensive rotational grazing limit diet quality ...

    African Journals Online (AJOL)

    Longer rest periods for intensive rotational grazing limit diet quality of sheep without enhancing environmental benefits. ... This experiment was established to compare three intensive rotational grazing strategies (fast rotation [FR], average 57-day rest; slow rotation [SR], average 114-day rest; and flexible grazing [FX], based ...

  19. Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

    Science.gov (United States)

    Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

    2018-06-01

    Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

  20. Do successful agers live longer? The Vitality 90+ study.

    Science.gov (United States)

    Nosraty, Lily; Enroth, Linda; Raitanen, Jani; Hervonen, Antti; Jylhä, Marja

    2015-02-01

    To discover whether successful aging, understood as a multidimensional concept, predicts further survival in very old people. The population sample consisted of 1,370 persons aged 90 or over in the Vitality 90+ study. Four alternative models of successful aging were constructed, each of them consisting of physical, psychological, and social dimensions. Mortality was followed up after 4 and 7 years. Three out of four models significantly predicted survival at both follow-ups for the whole group. Separately, "success" in the physical, psychological, and social components was also associated with higher survival. The associations were stronger in women than in men. Successful aging, measured using physical, psychological, and social dimensions, predicts the length of future life in nonagenarians. © The Author(s) 2014.

  1. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  2. Effects of a single high dose of 55Fe in mice

    International Nuclear Information System (INIS)

    Laissue, J.A.; Burlington, H.; Cronkite, E.P.; Heldman, B.; Reincke, U.

    1979-01-01

    High doses of 55 Fe induced cytocide in maturing erythroid cells, due to the short-range deposition of decay energy. Organ damage at the time of death was evaluated in a group of 45 female mice of the C 57 BL/6 J strain given a single i.v. injection of 2,800 μCi, 1,400 μCi or 700 μCi of 55 FeCl 3 when 10 to 14 weeks old. A corresponding amount of cold iron was given to control animals by the same route. Radioiron-treated mice died spontaneously, or were killed when moribund. Mice given 2,800 μCi died after a median survival time of 27 days with severe depletion of hemopoietic cells in bone marrow and spleen, marked atrophy of lymphoid tissues and mild liver damage. After 1,400 μCi or 700 μCi, the median survival time was 117 and 439, respectively. In contrast, median survival was 847 days in control animals allowed to survive. In the two lower 55 Fe-dose groups, there was a dose-dependent pancytopenia. Atrophy of lymphoid tissues was moderate, and signs of liver damage slight. The degree of organ hemosiderosis in experimental and control animals was slight to moderate. Organ damage associated with deposition of cold iron was not apparent in tissue sections. Morphological signs of damage to non-hemopoietic organs such as the liver were not conspicuous. Direct radiation damage, primarily to the erythroid series, and competition for stem cells between the heavily depleted erythroid and the other hemopoietic cell lines must be considered among the possible factors leading to pancytopenia. Out of 14 55 Fe-treated mice who survived longer than 300 days developed tumors of hemopoietic and lymphoid tissues, or osteosarcomas. (orig./MG) [de

  3. Telomere length is longer in women with late maternal age

    DEFF Research Database (Denmark)

    Fagan, Erin; Sun, Fangui; Bae, Harold

    2017-01-01

    OBJECTIVE:: Maternal age at birth of last child has been associated with maternal longevity. The aim of this study was to determine whether older women with a history of late maternal age at last childbirth had a longer leukocyte telomere length than those with maternal age at last childbirth of 29...... died, but were at least 70 years old, were studied. Logistic regression models using generalized estimating equations were used to determine the association between tertiles of telomere length and maternal age at last childbirth, adjusting for covariates. RESULTS:: Age at birth of the last child...... in the first tertile. CONCLUSIONS:: These findings show an association between longer leukocyte telomere length and a later maternal age at birth of last child, suggesting that extended maternal age at last childbirth may be a marker for longevity....

  4. Issues of using Longer Heavier Vehicles on Roads

    Science.gov (United States)

    Matuszkova, R.; Heczko, M.; Cepil, J.; Radimsky, M.

    2018-03-01

    Many logistics companies aim to save on freight costs. Recently, not only on Czech roads and on motorways, longer and heavier vehicles that exceed dimensions’ limits appeared. For these vehicles, it is necessary to apply for a special permit, which is, however, much more liberal than the permit for oversized and overweight load transport. This paper informs about checking routes of these vehicles by swept path analysis and finding locations on roads that can generate both safety risks and traffic fluency problems.

  5. Kenya; Ex Post Assessment of Longer-Term Program Engagement

    OpenAIRE

    International Monetary Fund

    2008-01-01

    This paper discusses key findings of the Ex Post Assessment (EPA) of Longer-Term Program Engagement paper for Kenya. This EPA focuses on 1993–2007, when Kenya was engaged in four successive IMF arrangements. Macroeconomic policy design was broadly appropriate, and implementation was generally sound. Growth slowed in the 1990s, but picked up after the 2002 elections, reflecting buoyant global conditions, structural reforms, and a surge of private capital inflows. Monetary policies were complic...

  6. Children’s Brain Development Benefits from Longer Gestation

    Directory of Open Access Journals (Sweden)

    Elysia Poggi Davis

    2011-02-01

    Full Text Available Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging (MRI in 100 healthy right-handed six to ten year old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in grey matter density. Further, the benefit of longer gestation for brain development was present even when only full term infants were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

  7. Nuclear power plant life management and longer-term operation

    International Nuclear Information System (INIS)

    2006-01-01

    This book, prepared by NEA member country experts, contains data and analyses relevant to nuclear power plant life management and the plants' extended, longer-term operation (LTO). It addresses technical, economic and environmental aspects and provides insights into the benefits and challenges of plant life management and LTO. It will be of interest to policy makers and senior managers in the nuclear power sector and governmental bodies involved in nuclear power programme design and management. The data and information on current trends in nuclear power plant life management will be useful to researchers and analysts working in the field of nuclear energy system assessment. (authors)

  8. Female entrepreneurs in trouble: do their bad loans last longer?

    OpenAIRE

    Juri Marcucci; Paolo Emilio Mistrulli

    2013-01-01

    We investigate the duration of bad loans for a unique data set of sole proprietorships in Italy, finding that bad loans for female firms last longer. However, this result is mainly due to the fact that loans granted to female firms are less frequently written off than those to male ones, suggesting that for banks female firms might be more creditworthy than male firms. These findings are robust to censoring, alternative specifications of the distribution of bad loan duration and other bank-sp...

  9. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    International Nuclear Information System (INIS)

    Wang, Xin; Xiong, Xiao-Peng; Lu, Jiade; Zhu, Guo-Pei; He, Shao-Qin; Hu, Chao-Su; Ying, Hong-Mei

    2011-01-01

    High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time

  10. Survival of indicator organisms, e.g. E. coli in drinking water pipes

    DEFF Research Database (Denmark)

    Albrechtsen, Hans-Jørgen; Silhan, J.; Corfitzen, Charlotte B.

    2006-01-01

    The survival of E. coli was investigated in used drinking water pipes from households. The investigation showed that E. coli survived longer in plastic pipes than in cupper pipes and galvanized steel pipes. The investigation also showed longer survival at cold water temperatures (15?C) than at hot...

  11. Sexual intimacy in couples is associated with longer telomere length.

    Science.gov (United States)

    Cabeza de Baca, Tomás; Epel, Elissa S; Robles, Theodore F; Coccia, Michael; Gilbert, Amanda; Puterman, Eli; Prather, Aric A

    2017-07-01

    High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs. Analyses revealed no statistically significant associations of telomere length with current relationship satisfaction, daily support or conflict, or perceived stress. In contrast, women who reported any sexual intimacy during the course of the week had significantly longer telomeres measured in whole blood and PBMCs, but not in granulocytes. These relationships held covarying for age, body mass index, perceived stress, the relationship indices, and caregiver status. Sexual intimacy was not significantly related to PBMC telomerase activity. These data provide preliminary data that sexual intimacy is associated with longer telomere length. Future studies investigating these associations are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

    Directory of Open Access Journals (Sweden)

    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  13. Timely bystander CPR improves outcomes despite longer EMS times.

    Science.gov (United States)

    Park, Gwan Jin; Song, Kyoung Jun; Shin, Sang Do; Lee, Kyung Won; Ahn, Ki Ok; Lee, Eui Jung; Hong, Ki Jeong; Ro, Young Sun

    2017-08-01

    This study aimed to determine the impact of bystander CPR on clinical outcomes in patients with increasing response time from collapse to EMS response. A population-based observational study was conducted in patients with witnessed out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology from 2012 to 2014. The time interval from collapse to CPR by EMS providers was categorized into quartile groups: fastest group (bystander CPR and the time interval from collapse to CPR by EMS providers. A total of 15,354 OHCAs were analyzed. Bystander CPR was performed in 8591 (56.0%). Survival to hospital discharge occurred in 1632 (10.6%) and favorable neurological outcome in 996 (6.5%). In an interaction model of bystander CPR, compared to the fastest group, adjusted odds ratios (AORs) (95% CIs) for survival to discharge were 0.89 (0.66-1.20) in the fast group, 0.76 (0.57-1.02) in the late group, and 0.52 (0.37-0.73) in the latest group. For favorable neurological outcome, AORs were 1.12 (0.77-1.62) in the fast group, 0.90 (0.62-1.30) in the late group, 0.59 (0.38-0.91) in the latest group. The survival from OHCA decreases as the ambulance response time increases. The increase in mortality and worsening neurologic outcomes appear to be mitigated in those patients who receive bystander CPR. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Dwarf Mice and Aging.

    Science.gov (United States)

    Masternak, Michal M; Darcy, Justin; Victoria, Berta; Bartke, Andrzej

    2018-01-01

    Dwarf mice have been studied for many decades, however, the focus of these studies shifted in 1996 when it was shown by Brown-Borg and her coworkers that Ames dwarf (Prop1 df ) mice are exceptionally long-lived. Since then, Snell dwarf (Pit1 dw ) and growth hormone receptor knockout (GHR-KO, a.k.a. Laron dwarf) mice were also shown to be exceptionally long-lived, presumably due to their growth hormone (GH)-deficiency or -resistance, respectively. What is of equal importance in these dwarf mice is their extended health span, that is, these animals have a longer period of life lived free of frailty and age-related diseases. This review article focuses on recent studies conducted in these dwarf mice, which concerned brown and white adipose tissue biology, microRNA (miRNA) profiling, as well as early-life dietary and hormonal interventions. Results of these studies identify novel mechanisms linking reduced GH action with extensions of both life span and health span. Copyright © 2017. Published by Elsevier Inc.

  15. Longer wait times affect future use of VHA primary care.

    Science.gov (United States)

    Wong, Edwin S; Liu, Chuan-Fen; Hernandez, Susan E; Augustine, Matthew R; Nelson, Karin; Fihn, Stephan D; Hebert, Paul L

    2017-07-29

    Improving access to the Veterans Health Administration (VHA) is a high priority, particularly given statutory mandates of the Veterans Access, Choice and Accountability Act. This study examined whether patient-reported wait times for VHA appointments were associated with future reliance on VHA primary care services. This observational study examined 13,595 VHA patients dually enrolled in fee-for-service Medicare. Data sources included VHA administrative data, Medicare claims and the Survey of Healthcare Experiences of Patients (SHEP). Primary care use was defined as the number of face-to-face visits from VHA and Medicare in the 12 months following SHEP completion. VHA reliance was defined as the number of VHA visits divided by total visits (VHA+Medicare). Wait times were derived from SHEP responses measuring the usual number of days to a VHA appointment with patients' primary care provider for those seeking immediate care. We defined appointment wait times categorically: 0 days, 1day, 2-3 days, 4-7 days and >7 days. We used fractional logistic regression to examine the relationship between wait times and reliance. Mean VHA reliance was 88.1% (95% CI = 86.7% to 89.5%) for patients reporting 0day waits. Compared with these patients, reliance over the subsequent year was 1.4 (p = 0.041), 2.8 (p = 0.001) and 1.6 (p = 0.014) percentage points lower for patients waiting 2-3 days, 4-7 days and >7 days, respectively. Patients reporting longer usual wait times for immediate VHA care exhibited lower future reliance on VHA primary care. Longer wait times may reduce care continuity and impact cost shifting across two federal health programs. Copyright © 2017. Published by Elsevier Inc.

  16. The effect of embryonal thymic calf extracts on neonatally thymectomized mice and on mice lethally irradiated with gamma rays

    International Nuclear Information System (INIS)

    Czaplicki, J.; Blonska, B.; Stec, L.

    1981-01-01

    The effect of embryonal thymic calf extracts (ETCE) on mice thymectomized at birth was investigated. ETCE was found to induce an increase in leukopenia and decrease in the level of serum gamma globulins; it also reduced survival time in mice. The effect of ETCE on lethally irradiated mice was also examined. Only long-term administration of ETCE prior to gamma irradiation at 750 rad prolonged the survival time of mice (40% permanent survival) as compared with irradiated controls; the leukocytes from mice retained mitotic capability. Neither long-term treatment with ETCE prior to irradiation at 1000 rad, nor short-term administration prior to 750 rad affected survival time. ETCE administered after irradiation of mice with 750 rad caused a rapid decrease in blood leukocytes and a significantly lowered survival time. (Auth.)

  17. Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout

    Science.gov (United States)

    Balbo, Bruno E.; Amaral, Andressa G.; Fonseca, Jonathan M.; de Castro, Isac; Salemi, Vera M.; Souza, Leandro E.; dos Santos, Fernando; Irigoyen, Maria C.; Qian, Feng; Chammas, Roger; Onuchic, Luiz F.

    2016-01-01

    Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations, in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1cond/cond:Nestincre (CYG+) cystic mice exposed to increased blood pressure, at 5–6 and 20–24 weeks of age, and Pkd1+/− (HTG+) noncystic mice at 5–6 and 10–13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1cond/cond and Pkd1+/+ controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1cond/cond:Nestincre;Lgals3−/− (CYG−) and Pkd1+/−;Lgals3−/− (HTG−) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from their controls. CYG− and HTG− showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1V/V; VVG+) showed that Pkd1V/V;Lgals3−/− (VVG−) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG− and VVG− animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype. PMID:27475230

  18. Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

    Science.gov (United States)

    Lemieux, Maxime; Laflamme, Olivier D; Thiry, Louise; Boulanger-Piette, Antoine; Frenette, Jérôme; Bretzner, Frédéric

    2016-03-01

    Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control. We investigated the motor and locomotor functions of DSCAM(2J) mutant mice through a combination of anatomical, kinematic, force, and electromyographic recordings. With respect to wild-type mice, DSCAM(2J) mice displayed a longer swing phase with a limb hyperflexion at the expense of a shorter stance phase during locomotion. Furthermore, electromyographic activity in the flexor and extensor muscles was increased and coactivated over 20% of the step cycle over a wide range of walking speeds. In contrast to wild-type mice, which used lateral walk and trot at walking speed, DSCAM(2J) mice used preferentially less coordinated gaits, such as out-of-phase walk and pace. The neuromuscular junction and the contractile properties of muscles, as well as their muscle spindles, were normal, and no signs of motor rigidity or spasticity were observed during passive limb movements. Our study demonstrates that the DSCAM mutation induces dystonic hypertonia and a disruption of locomotor gaits. Copyright © 2016 the American Physiological Society.

  19. Wound healing and longevity: lessons from long-lived αMUPA mice.

    Science.gov (United States)

    Yanai, Hagai; Toren, Dimitri; Vierlinger, Klemens; Hofner, Manuela; Nöhammer, Christa; Chilosi, Marco; Budovsky, Arie; Fraifeld, Vadim E

    2015-03-01

    Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage.

  20. Immunobiology of congenitally athymic-asplenic mice

    International Nuclear Information System (INIS)

    Gershwin, M.E.; Ahmed, A.; Ikeda, R.M.; Shifrine, M.; Wilson, F.

    1978-01-01

    A study has been made of congenitally athymic-asplenic mice obtained by the mating of nude by hereditarily asplenic (Dh/+) mice. The mice survived for up to 9 months, under specific pathogen-free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice were similar to those of their nude and asplenic littermates, there were a number of major immunologic differences. The athymic-asplenic mice appeared more immunologically compromised than nude mice. There was an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. There was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired. (author)

  1. Immunization with DNA plasmids coding for crimean-congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice

    DEFF Research Database (Denmark)

    Hinkula, Jorma; Devignot, Stéphanie; Åkerström, Sara

    2017-01-01

    , there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice...... with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type...

  2. Docetaxel chronopharmacology in mice.

    Science.gov (United States)

    Tampellini, M; Filipski, E; Liu, X H; Lemaigre, G; Li, X M; Vrignaud, P; François, E; Bissery, M C; Lévi, F

    1998-09-01

    Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms

  3. [Diabetic neuropathy: therapeutic nihilism is no longer acceptable].

    Science.gov (United States)

    Haslbeck, Manfred

    2007-05-21

    The repeatedly expressed doubts about the value of an effective therapy for diabetic neuropathies are no longer acceptable. Today a number of excellent longitudinal and cross-sectional studies, i.e. DCCT, Steno 2, DCCT/EDIC, European Diabetes Prospective Complications Study, are available. The attending physician should make every effort to diagnose diabetic neuropathies as soon as possible with all their multivarious manifestations. Treatment must be promptly, aggressively and multifactorially as described in evidence-based guidelines. In principle, the same risk factors apply to neuropathy in type 1 and type 2 diabetes as for macro-angiopathy and microangiopathy. Therapy focuses on establishing near-normal diabetes and blood pressure control, lipid management, intensive patient education, avoidance of exogenous noxae such as alcohol and nicotine and if necessary, an effective therapy of neuropathic pain. The objective of all diagnostic and preventive efforts must be always to avoid the development of the diabetic neuropathic foot syndrome, which is the most important end stage of somatic and autonomic diabetic neuropathy.

  4. Needle Decompression in Appalachia Do Obese Patients Need Longer Needles?

    Directory of Open Access Journals (Sweden)

    Carter, Thomas Edward

    2013-11-01

    Full Text Available Introduction: Needle decompression of a tension pneumothorax can be a lifesaving procedure. It requires an adequate needle length to reach the chest wall to rapidly remove air. With adult obesity exceeding one third of the United States population in 2010, we sought to evaluate the proper catheter length that may result in a successful needle decompression procedure. Advance Trauma Life Support (ATLS currently recommends a 51 millimeter (mm needle, while the needles stocked in our emergency department are 46 mm. Given the obesity rates of our patient population, we hypothesize these needles would not have a tolerable success rate of 90%. Methods: We retrospectively reviewed 91 patient records that had computed tomography of the chest and measured the chest wall depth at the second intercostal space bilaterally. Results: We found that 46 mm needles would only be successful in 52.7% of our patient population, yet the ATLS recommended length of 51 mm has a success rate of 64.8%. Therefore, using a 64 mm needle would be successful in 79% percent of our patient population. Conclusion: Use of longer length needles for needle thoracostomy is essential given the extent of the nation’s adult obesity population. [West J Emerg Med. 2013;14(6:650-652.

  5. Surviving Sengstaken.

    Science.gov (United States)

    Jayakumar, S; Odulaja, A; Patel, S; Davenport, M; Ade-Ajayi, N

    2015-07-01

    To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Peruvian Tropical Glacier May Survive Longer Than Previously Thought: Landsat Image Analysis of Nevado Coropuna Ice Cap, Peru

    Science.gov (United States)

    Kochtitzky, W. H.; Edwards, B. R.; Marino, J.; Manrique, N.

    2015-12-01

    Nevado Coropuna is a large volcanic complex in southern Peru (15.56°S, 72.62°N; 6,425 m). The complex is approximately 12 km east-west and 8 km north-south with elevation from ~4,500 m at the base to over 6,000 m at the highest points. This ice cap is the largest hosted by a volcano in the tropics, and one of the ten biggest ice masses in the tropics. Previous workers have predicted that the Coropuna ice cap will completely melt by 2050. We present a new analysis of historic satellite imagery to test this hypothesis. In this study, ice and snow are classified based on unique spectral signatures including spectral band thresholds, Normalized Difference Snow Index, and Band 4/5 ratio. Landsat scenes (L2, 4, 5, 7, and 8) from 1975 to present in addition to one SPOT scene (2013) are used. Previous workers used images from June and July, which are peak snow periods in southern Peru, leading to overestimates of ice area. This study uses November and December images when snow is at an annual minimum. Annual equilibrium line altitudes are calculated for each end of year image (November/December). The glaciers of Nevado Coropuna were found to be shrinking at ~0.5 km2/yr, which is ~1/3 the rate previously published. In this study, SPOT (1.5 m resolution) and Landsat 7 ETM scenes from November 23 and 26, 2013 respectively were used to calibrate the spectral band threshold classification. While this study suggests that the ice cap of Coropuna will persist until 2100 given current rates, water quantity and security remains a concern for Peruvian agriculture. Coropuna is an active volcano, so it poses great risk to surrounding inhabitants from lahars, flooding, and debris avalanches. Our new data suggest that these will continue to be risks late into this century.

  7. Agonist of the adenosine A(3) receptor, IB-MECA, and inhibitor of cyclooxygenase-2, meloxicam, given alone or in a combination early after total body irradiation enhance survival of gamma-irradiated mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2014-01-01

    Roč. 53, č. 1 (2014), s. 211-215 ISSN 0301-634X R&D Projects: GA ČR(CZ) GA305/08/0158; GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : Ionizing radiation * Acute radiation disease * Survival Subject RIV: BO - Biophysics Impact factor: 1.528, year: 2014

  8. Fledgling survival increases with development time and adult survival across north and south temperate zones

    Science.gov (United States)

    Lloyd, Penn; Martin, Thomas E.

    2016-01-01

    Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

  9. Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma.

    Science.gov (United States)

    Crommentuijn, Matheus H W; Maguire, Casey A; Niers, Johanna M; Vandertop, W Peter; Badr, Christian E; Würdinger, Thomas; Tannous, Bakhos A

    2016-04-01

    Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. In U87 cells, conditioned medium from AAV2-sTRAIL expressing cells combined with lan C induced 80% cell death. Similarly, lan C sensitized primary GBM spheres to sTRAIL causing over 90% cell death. In mice bearing intracranial U87 tumors treated with AAVrh.8-sTRAIL, administration of lan C caused a decrease in tumor-associated Fluc signal, while tumor size increased within days of stopping the treatment. Another round of lan C treatment re-sensitized GBM tumor to sTRAIL-induced cell death. AAVrh.8-sTRAIL treatment alone and combined with lanatoside C resulted in a significant decrease in tumor growth and longer survival of mice bearing orthotopic invasive GBM brain tumors. In summary, AAV-sTRAIL combined with lanatoside C induced cell death in U87 glioma cells and patient-derived GBM neural spheres in culture and in vivo leading to an increased in overall mice survival. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Against all odds: genocidal trauma is associated with longer life-expectancy of the survivors.

    Directory of Open Access Journals (Sweden)

    Abraham Sagi-Schwartz

    Full Text Available Does surviving genocidal experiences, like the Holocaust, lead to shorter life-expectancy? Such an effect is conceivable given that most survivors not only suffered psychosocial trauma but also malnutrition, restriction in hygienic and sanitary facilities, and lack of preventive medical and health services, with potentially damaging effects for later health and life-expectancy. We explored whether genocidal survivors have a higher risk to die younger than comparisons without such background. This is the first population-based retrospective cohort study of the Holocaust, based on the entire population of immigrants from Poland to Israel (N = 55,220, 4-20 years old when the World War II started (1939, immigrating to Israel either between 1945 and 1950 (Holocaust group or before 1939 (comparison group; not exposed to the Holocaust. Hazard of death - a long-term outcome of surviving genocidal trauma - was derived from the population-wide official data base of the National Insurance Institute of Israel. Cox regression yielded a significant hazard ratio (HR = 0.935, CI (95% = 0.910-0.960, suggesting that the risk of death was reduced by 6.5 months for Holocaust survivors compared to non-Holocaust comparisons. The lower hazard was most substantial in males who were aged 10-15 (HR = 0.900, CI (95% = 0.842-0.962, i.e., reduced by 10 months or 16-20 years at the onset of the Holocaust (HR = 0.820, CI (95% = 0.782-0.859, i.e., reduced by18 months. We found that against all odds genocidal survivors were likely to live longer. We suggest two explanations: Differential mortality during the Holocaust and "Posttraumatic Growth" associated with protective factors in Holocaust survivors or in their environment after World War II.

  11. The induction of specific immunity against Schistosoma japonicum by exposure of mice to ultraviolet attenuated cercariae

    International Nuclear Information System (INIS)

    Moloney, N.A.; Bickle, Q.D.; Webbe, G.

    1985-01-01

    Mice can be partially protected against Schistosoma japonicum by prior exposure to ultraviolet (UV)-attenuated infections which fail to survive to the adult stage and produce no overt pathology in the host. Optimum resistance was induced by parasites exposed to 40 seconds of UV, significantly lower levels of resistance being stimulated by both shorter and longer exposures. No consistent relationship between the degree of resistance induced and the number of irradiated cercariae given could be demonstrated and equivocal results were obtained when comparing the efficacy of single and multiple vaccinations. Vaccinations with UV-attenuated cercariae given intraperitoneally (i.p.) were as efficacious as those given percutaneously but mice were as or more resistant to challenges given by the i.p. route, the possible reasons are discussed. There was no observed delay in the migration of the challenge, vaccinated mice being as resistant when perfused 6 or 3.5 weeks after challenge. Vaccination was species specific since mice exposed to either UV-attenuated S. japonicum cercariae or gamma-attenuated S. mansoni cercariae were resistant to homologous but not heterologous challenge. (author)

  12. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    Directory of Open Access Journals (Sweden)

    Zhu Guo-Pei

    2011-01-01

    Full Text Available Abstract Background High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. Methods 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. Results The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P 0.05. Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. Conclusions The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

  13. Effect of aging and radiation in mice of different genotypes

    International Nuclear Information System (INIS)

    Storer, J.B.

    1976-01-01

    Data are presented on the life span of nine inbred strains and five hybrid strains of mice based on 400 mice of each sex for inbred and 200 mice of each sex for hybrid. Some of these mice were exposed when 120 days old to 250 R or 450 R of x radiation delivered at a dose rate of 60 R/min. Data on strain, sample size, and mean survival times are presented in tables

  14. Curcumin attenuates the scurfy-induced immune disorder, a model of IPEX syndrome, with inhibiting Th1/Th2/Th17 responses in mice.

    Science.gov (United States)

    Lee, Gihyun; Chung, Hwan-Suck; Lee, Kyeseok; Lee, Hyeonhoon; Kim, Minhwan; Bae, Hyunsu

    2017-09-15

    Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period. C57BL/6 mice were separated into scurfy or wild-type litter mate groups by genotyping, and each group subsequently was separated into 2 subgroups that were fed a 1% curcumin containing or normal diet from the last day of breast-feeding. After weaning, pups were fed either a 1% curcumin containing or normal diet until all scurfy mice die for survival data. To elucidate immune cell proportions in spleen and lymph nodes, cells were analyzed by flowcytometry. Cellular cytokine production was accessed to investigate the effects of curcumin in T cell differentiation in vitro. Scurfy mice fed a 1% curcumin diet survived 4.0-fold longer compared to scurfy (92.5 days) mice fed a normal diet (23 days). A curcumin diet decreased all of the Th1/Th2/Th17 cell populations and attenuated diverse symptoms such as splenomegaly in scurfy mice. In vitro experiments showed that curcumin treatment directly decreased the Th1/Th2/Th17 cytokine production of IFN-γ, IL-4, and IL-17A in CD4 + T cells. Curcumin diet attenuated the scurfy-induced immune disorder, a model of IPEX syndrome, by inhibiting Th1/Th2/Th17 responses in mice. These results have implications for improving clinical therapy for patients with IPEX and other T cell related autoimmune diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Treatment of Experimental Acute Radiation Disease in Mice with Probiotics, Quinolones, and General Gnotobiological Isolation

    National Research Council Canada - National Science Library

    Korschunov, Valerji

    1998-01-01

    ...) on intestinal microflora, translocation, and mortality was studied in mice treated with 7.0 Gy radiation. Lactobacilli and bifidobacteria, selected by in vitro and in vivo methods, increased survival parameters of the mice...

  16. Tumor radiation responses and tumor oxygenation in aging mice

    International Nuclear Information System (INIS)

    Rockwell, S.

    1989-01-01

    EMT6 mouse mammary tumors transplanted into aging mice are less sensitive to radiation than tumors growing in young adult animals. The experiments reported here compare the radiation dose-response curves defining the survivals of tumor cells in aging mice and in young adult mice. Cell survival curves were assessed in normal air-breathing mice and in mice asphyxiated with N 2 to produce uniform hypoxia throughout the tumors. Analyses of survival curves revealed that 41% of viable malignant cells were severely hypoxic in tumors in aging mice, while only 19% of the tumor cells in young adult animals were radiobiologically hypoxic. This did not appear to reflect anaemia in the old animals. Treatment of aging animals with a perfluorochemical emulsion plus carbogen (95% O 2 /5% CO 2 ) increased radiation response of the tumors, apparently by improving tumor oxygenation and decreasing the number of severely hypoxic, radiation resistant cells in the tumors. (author)

  17. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    Unknown

    In the present work, we report radioadaptive response in terms of survival of ... Group 4: mice pre-treated with conditioning dose of 0⋅5 Gy ... week in mice exposed to 8 Gy. For mice .... The adaptive response is known to remain for a few hours.

  18. Immediate and Longer-Term Stressors and the Mental Health of Hurricane Ike Survivors

    OpenAIRE

    Lowe, Sarah R.; Tracy, Melissa; Cerdá, Magdalena; Norris, Fran H.; Galea, Sandro

    2013-01-01

    Previous research has documented that individuals exposed to more stressors during disasters and their immediate aftermath (immediate stressors) are at risk of experiencing longer-term postdisaster stressors. Longer-term stressors, in turn, have been found to play a key role in shaping postdisaster psychological functioning. Few studies have simultaneously explored the links from immediate to longer-term stressors, and from longer-term stressors to psychological functioning,...

  19. Schistosoma mansoni: aspectos quantitativos da fertilidade e sobrevida de vermes oriundos de cercárias irradiadas com 3 Krad, em camundongos Schistosoma mansoni: quantitative aspects of the fertility and survival of worms obtained from irradiated cercariae (3 Krad, in mice

    Directory of Open Access Journals (Sweden)

    Gileno de Sá Cardoso

    1990-02-01

    Full Text Available Quatro grupos de camundongos albinos (Mus musculus não isogênicos foram infectados transcutaneamente com cerca de 450 cercárias (das cepas LE e SJ do S. mansoni não irradiadas (grupos controles e irradiadas com 3 Krad de radiação gama proveniente de cobalto-60, com a finalidade de observar o efeito da irradiação gama sobre a fertilidade das fêmeas e a sobrevida dos vermes no sistema porta. A partir do 33º dia ocorre uma certa estabilidade na população dos vermes sobreviventes, ficando esta população constante, notadamente em relação à cepa LE, até o final das observações (90º dia. Concluiu-se que esta dose de radiação gama impede a produção de ovos dos vermes em 98,1% dos camundongos infectados, sendo mortos todos os ovos detectados; as fêmeas são mais resistentes à irradiação e o efeito desta sobre a mortalidade dos machos somente se torna estatisticamente significativo a partir do 61º dia de infecção. O longo tempo de permanência de vermes adultos irradiados estéreis no sistema porta de camundongos e o seu provável envolvimento no desenvolvimento de imunoproteção, tipo imunidade concomitante sem as implicações imunopatológicas para o hospedeiro, são discutidos nesse trabalho.The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus, experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains, by transcutaneous route. The cercariae used were a non-irradiated (control groups, and b irradiated with 3 Krad of gamma irradiation (Co-60. From the 33rd day on, some estability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90th day, notedly in relation to the LE strain. Thus, it was concluded that gamma irradiation (at the dose of 3 Krad is able to hinder the worm egg

  20. Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production.

    Directory of Open Access Journals (Sweden)

    Mitsuharu Matsumoto

    Full Text Available BACKGROUND: Chronic low-grade inflammation is recognized as an important factor contributing to senescence and age-related diseases. In mammals, levels of polyamines (PAs decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. Reductions in intestinal luminal PAs levels have been associated with intestinal barrier dysfunction. The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations. METHODOLOGY/PRINCIPAL FINDINGS: We supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared using Kaplan-Meier survival curves. LKM512-treated mice survived significantly longer than controls (P<0.001; moreover, skin ulcers and tumors were more common in the control mice. We then analyzed inflammatory and intestinal conditions by measuring several markers using HPLC, ELISA, reverse transcription-quantitative PCR, and histological slices. LKM512 mice showed altered 16S rRNA gene expression of several predominant intestinal bacterial groups. The fecal concentrations of PAs, but not of short-chain fatty acids, were significantly higher in LKM512-treated mice (P<0.05. Colonic mucosal function was also better in LKM512 mice, with increased mucus secretion and better maintenance of tight junctions. Changes in gene expression levels were evaluated using the NimbleGen mouse DNA microarray. LKM512 administration also downregulated the expression of ageing-associated and inflammation-associated genes and gene expression levels in 21-month-old LKM512-treated mice resembled those in 10-month-old untreated (younger mice. CONCLUSION/SIGNIFICANCE: Our study demonstrated increased longevity in mice following probiotic treatment with LKM512, possibly due to the suppression of chronic low-grade inflammation in the colon

  1. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  2. Immuno-efficacy of DNA vaccines encoding PLP1 and ROP18 against experimental Toxoplasma gondii infection in mice.

    Science.gov (United States)

    Chen, Yajun; Yu, Miao; Hemandez, J A; Li, Jiexi; Yuan, Zi-Guo; Yan, Haikuo

    2018-05-01

    We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain

    DEFF Research Database (Denmark)

    Leone, Dino P; Srinivasan, Karpagam; Brakebusch, Cord

    2010-01-01

    family member, Cdc42, affects the polarity and proliferation of radial glial cells in the VZ. Here, we show that another family member, Rac1, is required for the normal proliferation and differentiation of SVZ progenitors and for survival of both VZ and SVZ progenitors. A forebrain-specific loss of Rac1...... leads to an SVZ-specific reduction in proliferation, a concomitant increase in cell cycle exit, and premature differentiation. In Rac1 mutants, the SVZ and VZ can no longer be delineated, but rather fuse to become a single compact zone of intermingled cells. Cyclin D2 expression, which is normally...... expressed by both VZ and SVZ progenitors, is reduced in Rac1 mutants, suggesting that the mutant cells differentiate precociously. Rac1-deficient mice can still generate SVZ-derived upper layer neurons, indicating that Rac1 is not required for the acquisition of upper layer neuronal fates, but instead...

  4. Tularemia induces different biochemical responses in BALB/c mice and common voles

    Directory of Open Access Journals (Sweden)

    Vitula Frantisek

    2009-06-01

    Full Text Available Abstract Background Both BALB/c mice and common voles (Microtus arvalis are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection. Methods Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU pro toto. Results Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles. On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found. Conclusion As differences in lipid metabolism and the total antioxidant capacity of highly susceptible rodent species were demonstrated, the role of triglycerides, cholesterol and antioxidants in tularemic sepsis should be further investigated.

  5. A gene expression signature associated with survival in metastatic melanoma

    Science.gov (United States)

    Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

    2006-01-01

    Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

  6. A gene expression signature associated with survival in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Rossi Carlo R

    2006-11-01

    Full Text Available Abstract Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM to identify genes associated with patient survival, and supervised principal components (SPC to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.

  7. Network survivability performance

    Science.gov (United States)

    1993-11-01

    This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

  8. Euthanasia of neonatal mice with carbon dioxide

    Science.gov (United States)

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

    2005-01-01

    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  9. The survival of Coxiella burnetii in soils

    Science.gov (United States)

    Evstigneeva, A. S.; Ul'Yanova, T. Yu.; Tarasevich, I. V.

    2007-05-01

    Coxiella burnetii is a pathogen of Q-fever—a widespread zoonosis. The effective adaptation of C. burnetii to intracellular existence is in contrast with its ability to survive in the environment outside the host cells and its resistance to chemical and physical agents. Its mechanism of survival remains unknown. However, its survival appears to be related to the developmental cycle of the microorganism itself, i.e., to the formation of its dormant forms. The survival of Coxiella burnetii was studied for the first time. The pathogenic microorganism was inoculated into different types of soil and cultivated under different temperatures. The survival of the pathogen was verified using a model with laboratory animals (mice). Viable C. burnetii were found in the soil even 20 days after their inoculation. The relationship between the organic carbon content in the soils and the survival of C. burnetii was revealed. Thus, the results obtained were the first to demonstrate that the soil may serve as a reservoir for the preservation and further spreading of the Q-fever pathogen in the environment, on the one hand, and reduce the risk of epidemics, on the other.

  10. Diurnal variations in proliferation and crypt survival suggest a small target cell population in mouse colon

    International Nuclear Information System (INIS)

    Dobbin, J.; Hamilton, E.

    1986-01-01

    Male C57BLasup(t) mice of two ages, 3-5 months (young) and 14-15 months (old) were given 11 or 15Gy whole body irradiation at different times through the day. The mice were killed after 4.5 days and the number of surviving crypts per circumference of jejunum, ileum, transverse colon and descending colon were scored. These results show crypt survival in the small and large intestine of 15-month-old mice. In the ileum the maximum crypt survival was found at 04.00 h and the minimum at 08.00 h. In the jejunum and both regions of the colon the maximum crypt survival occurred at 16.00 h. The nadir of crypt survival after 15 Gy was at 04.00 h in the jejunum and at 20.00 and 24.00 h in the transverse and descending colon, respectively. In young mice, crypt survival levels were similar to those found in old animals except at 04.00 h. when survival in the jejunum and ileum fell to 0.0004+-0.0002 and 0.0007+-0.0004, respectively. The lowest crypt survival in the colon of young mice also occurred at 04.00 h and in all four tissues the greatest number of crypts survived irradiation at 24.00 h. (author)

  11. Longer-term effects of pine and eucalypt plantations on streamflow

    CSIR Research Space (South Africa)

    Scott, DF

    2008-10-01

    Full Text Available The longer-term effects of afforestation with Pinus radiata and Eucalyptus grandis on streamflows were analyzed using data from two paired-catchment experiments in South Africa. The experiments are rare in that they have been maintained over longer...

  12. Trends in scale and shape of survival curves.

    Science.gov (United States)

    Weon, Byung Mook; Je, Jung Ho

    2012-01-01

    The ageing of the population is an issue in wealthy countries worldwide because of increasing costs for health care and welfare. Survival curves taken from demographic life tables may help shed light on the hypotheses that humans are living longer and that human populations are growing older. We describe a methodology that enables us to obtain separate measurements of scale and shape variances in survival curves. Specifically, 'living longer' is associated with the scale variance of survival curves, whereas 'growing older' is associated with the shape variance. We show how the scale and shape of survival curves have changed over time during recent decades, based on period and cohort female life tables for selected wealthy countries. Our methodology will be useful for performing better tracking of ageing statistics and it is possible that this methodology can help identify the causes of current trends in human ageing.

  13. Do Not ignore pulmonary hypertension any longer. It’s time to deal with it!

    Directory of Open Access Journals (Sweden)

    Ahmad Mirdamadi

    2011-08-01

    tromboembolic attacks in check.Then,It was time of revolution in pulmonary hypertension management,With the emergence of Advanced PH treatment science of medicine became able to seriously deal with  PH.This new strategy were showed to be able preventing mortality in PH patients’(5,Figure1Prostacycline showed that it is possible to enhance PH patients’ chance of survival. Phosphodiasterase inhibitor drugs, which were used for treating impotency for a long time, were demonstrated to be effective for reducing pulmonary pressure. Eventually, endotheline receptors were targeted.By the advent of endothelin receptor blockers such as Brosentan, physicians’ chances of helping PH patients were further improved.Today, with advanced PH treatment, PH is not counted as before and the science of medicine as a failed discipline.It is important to not forgetting PH in patients,especially ill patients or intractable to traditional treatment, in surgery wards or obstetric,pediatric,internal medicine,ICU or CCU wards of hospitals. By timely diagnosis, it will be possible to control  PH patients in an effective way and to enhance their chance of survival.So,It is time now to pay more attention to PH,Don’t ignore it any longer and it’s time to deal with it

  14. Rainfall during parental care reduces reproductive and survival components of fitness in a passerine bird

    OpenAIRE

    ?berg, Meit; Arlt, Debora; P?rt, Tomas; Laugen, Ane T; Eggers, S?nke; Low, Matthew

    2014-01-01

    Adverse weather conditions during parental care may have direct consequences for offspring production, but longer-term effects on juvenile and parental survival are less well known. We used long-term data on reproductive output, recruitment, and parental survival in northern wheatears (Oenanthe oenanthe) to investigate the effects of rainfall during parental care on fledging success, recruitment success (juvenile survival), and parental survival, and how these effects related to nestling age,...

  15. GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

    OpenAIRE

    Brown-Borg, Holly M.; Bartke, Andrzej

    2012-01-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

  16. Olfactory neuroblastoma: 14-year experience at an Australian tertiary centre and the role for longer-term surveillance.

    Science.gov (United States)

    Schmidt, C; Potter, N; Porceddu, S; Panizza, B

    2017-07-01

    Olfactory neuroblastoma is a rare sinonasal malignancy, with poorly defined treatment protocols. Management at a tertiary centre was retrospectively evaluated to inform future treatment and follow up. Cases treated with curative intent (2000-2014) were included. Data were collected, and overall and disease-free survival rates were calculated. Eleven cases were identified, with a median follow up of 87 months. One patient was Kadish stage A, one was stage B, eight were stage C and one was stage D. The latter patient underwent chemoradiotherapy alone. The remaining patients proceeded to: endoscopic-assisted wide local excision (n = 2), anterior craniofacial resection (n = 4) or endoscopic craniofacial resection (n = 4). No patients had primary nodal disease or elective neck treatment. One patient had neoadjuvant chemoradiation. Six patients had post-operative radiotherapy; three received adjuvant chemotherapy. Two patients had late cervical node failure, and proceeded to neck dissection and post-operative radiotherapy. Two patients had late local recurrence. Ten-year overall and disease-free survival rates were 68.2 and 46.7 per cent, respectively. Longer-term follow up is supported given the incidence of late regional and local recurrence. Prophylactic treatment of cervical nodes in locally advanced disease is an area for further investigation.

  17. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  18. Cloning Mice.

    Science.gov (United States)

    Ogura, Atsuo

    2017-08-01

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

  19. ASURV: Astronomical SURVival Statistics

    Science.gov (United States)

    Feigelson, E. D.; Nelson, P. I.; Isobe, T.; LaValley, M.

    2014-06-01

    ASURV (Astronomical SURVival Statistics) provides astronomy survival analysis for right- and left-censored data including the maximum-likelihood Kaplan-Meier estimator and several univariate two-sample tests, bivariate correlation measures, and linear regressions. ASURV is written in FORTRAN 77, and is stand-alone and does not call any specialized libraries.

  20. Can You Lengthen Your Life? Researchers Explore How To Stay Healthy Longer

    Science.gov (United States)

    ... a longer, healthier life. “There’s no question that smoking is a hard habit to break. But data suggest that from the moment you stop smoking, there are health benefits. So it’s worthwhile making ...

  1. Longer combination vehicles : an estimation of their benefits and public perception of their use.

    Science.gov (United States)

    2012-03-01

    Longer Combination Vehicles (LCVs) are able to carry more freight than conventional single trailer trucks. As a result, these trucks can increase : efficiencies and benefits for freight movements as less fuel and less labor is used per ton of cargo. ...

  2. Science 101: Why Does It Take Longer to Boil Potatoes at High Altitudes?

    Science.gov (United States)

    Robertson, Bill

    2017-01-01

    Why Does It Take Longer to Boil Potatoes at High Altitudes? This column provides background science information for elementary teachers. This month's issue looks at why water boils at different temperatures at different altitudes.

  3. CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice

    International Nuclear Information System (INIS)

    Wang, Lifeng; Chen, Haijin; Yu, Jinlong; Lin, Xiaohua; Qi, Jia; Cui, Chunhui; Xie, Lang; Huang, Shuxin

    2016-01-01

    Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells. Using in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate–labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice. In each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups. CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor

  4. Immediate and Longer-Term Stressors and the Mental Health of Hurricane Ike Survivors

    Science.gov (United States)

    Lowe, Sarah R.; Tracy, Melissa; Cerdá, Magdalena; Norris, Fran H.; Galea, Sandro

    2014-01-01

    Previous research has documented that individuals exposed to more stressors during disasters and their immediate aftermath (immediate stressors) are at risk of experiencing longer-term postdisaster stressors. Longer-term stressors, in turn, have been found to play a key role in shaping postdisaster psychological functioning. Few studies have simultaneously explored the links from immediate to longer-term stressors, and from longer-term stressors to psychological functioning, however. Additionally, studies have inadequately explored whether postdisaster psychological symptoms influence longer-term stressors. In the current study, we aimed to fill these gaps. Participants (N = 448) were from population-based study of Hurricane Ike survivors and completed assessments 2–5 months (Wave 1), 5–9 months (Wave 2) and 14–18 months (Wave 3) postdisaster. Through path analysis, we found that immediate stressors, assessed at Wave 1, were positively associated with Wave 2 and Wave 3 stressors, which in turn were positively associated with Wave 2 and Wave 3 posttraumatic stress and depressive symptoms. Wave 2 posttraumatic stress symptoms were positively associated with Wave 3 stressors, and Wave 1 depressive symptoms were positively associated with Wave 2 stressors. The findings suggest that policies and interventions can reduce the impact of disasters on mental health by preventing and alleviating both immediate and longer-term postdisaster stressors. PMID:24343752

  5. Multiple neoplasms, single primaries, and patient survival

    International Nuclear Information System (INIS)

    Amer, Magid H

    2014-01-01

    Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991). Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition

  6. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.

    Directory of Open Access Journals (Sweden)

    Atefeh Razazan

    Full Text Available One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE containing monophosphoryl lipid A (MPL adjuvant (DMPC-DMPG-DOPE-MPL-Gp2. BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.

  7. Surviving mousepox infection requires the complement system.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Moulton

    2008-12-01

    Full Text Available Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/- or Factor B(-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.

  8. Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation

    Directory of Open Access Journals (Sweden)

    Monique Richter

    2014-07-01

    Full Text Available Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235 and an immunomodulatory T cell epitope from the tetanus toxin or tuberculosis antigen Ag85B. Importantly, the designed vaccine combining Alzheimer’s disease (AD specific B cell epitopes with foreign (bacterial T cell epitopes induced fast immune responses with high IgG1 titers after prophylactic immunization that subsequently decreased over the observation period. The effectiveness of the immunization was surveyed by evaluating the animal behavior, as well as the pathology in the brain by biochemical and histochemical techniques. Immunized mice clearly lived longer with reduced paralysis than placebo-treated mice. Additionally, they performed significantly better in rotarod and beam walk tests at the age of 20 weeks, indicating that the disease development was slowed down. Forty-eight weeks old vaccinated mice passed the beam walk test significantly better than control animals, which together with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.

  9. Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿

    Science.gov (United States)

    Budd, Alison; Alleva, Lisa; Alsharifi, Mohammed; Koskinen, Aulikki; Smythe, Victoria; Müllbacher, Arno; Wood, Jeff; Clark, Ian

    2007-01-01

    Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain. PMID:17562808

  10. [Effect of hedgehog hydnum on the delay of fatigue in mice].

    Science.gov (United States)

    Lu, Y H; Xin, C L; Zhou, Y F; Liu, X W; Chi, J W; Chang, X

    1996-02-01

    Two groups of mice were fed with either hedgehog hydnum powder or extract for sixty days. For the assay of fatigue, the activity of serum lactate dehydrogenase, the serum urea nitrogen content, blood lactic acid, hepatic and muscular glycogen, and the physical stamina of the mice were determined. The activity of serum lactate dehydrogenase and the hepatic and muscular glycogen content in the experimental mice were evidently higher than that in the control mice (P increase in blood lactic acid and serum urea nitrogen in the experimental mice was significantly lower than that in the control mice (P stamina swimming, the experimental mice drowned after a longer period of time than the control mice (P stamina and delaying fatigue in mice.

  11. Network ties and survival

    DEFF Research Database (Denmark)

    Acheampong, George; Narteh, Bedman; Rand, John

    2017-01-01

    Poultry farming has been touted as one of the major ways by which poverty can be reduced in low-income economies like Ghana. Yet, anecdotally there is a high failure rate among these poultry farms. This current study seeks to understand the relationship between network ties and survival chances...... of small commercial poultry farms (SCPFs). We utilize data from a 2-year network survey of SCPFs in rural Ghana. The survival of these poultry farms are modelled using a lagged probit model of farms that persisted from 2014 into 2015. We find that network ties are important to the survival chances...... but this probability reduces as the number of industry ties increases but moderation with dynamic capability of the firm reverses this trend. Our findings show that not all network ties aid survival and therefore small commercial poultry farmers need to be circumspect in the network ties they cultivate and develop....

  12. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-01-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  13. Survivability and Hope

    Science.gov (United States)

    ... Current Issue Past Issues Special Section Survivability and Hope Past Issues / Spring 2007 Table of Contents For ... cure or long-term survivorship." This message of hope is a hallmark of the latest advances in ...

  14. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-02-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  15. Analysis of Prolonged Hospitalizations (Longer than 7 days: 115 Lung Cancer 
Patients after Video Assistant Thoracic Surgery (VATS

    Directory of Open Access Journals (Sweden)

    Liang DAI

    2018-03-01

    Full Text Available Background and objective Thoracoscopic surgery has gradually become the major procedure for lung cancer surgery in our department. Its characteristics are minimal trauma and quick recovery, which make approximately 90% of patients discharge from the hospital after surgery. However, the postoperative complications still happen now and then. We analyzed the patients who had been hospitalized for longer than 7 days after thoracoscopic lung cancer surgery, aiming to summarize the types and risk factors of complications, and improve postoperative safety of patients. Methods The data were come from the prospective database of Thoracic Surgery Unit One in Peking Cancer Hospital, and patients that underwent thoracoscopic pulmonary surgery between Jan. 2010 and Dec. 2014 with length of stay more than 7 days were included in the study. The classifications of the complications were investigated and graded as mild or severe complications according to modified Claviengrading, the relationship between clinical factors and degrees of complications was also analyzed. Results The hospitalization of 115 cases were longer than 7 days after surgery, accounting for 10.3% (115/1,112 of the whole patients that underwent surgery during the same period. Eighty-one cases had mild complications, accounting for 7.3% (81/1,112 of the whole cases that underwent surgery during the same period and 70.4% (81/115 of the cases with prolonged length of stay; the proportions of severe complications in both groups were 3.1% (34/1,112 and 29.6% (34/115, respectively; and the proportions of complications that caused perioperative deaths were 0.18% (2/1112 and 1.7% (2/115, respectively. Among all the postoperative complications, the most common was air leakage for more than 5 days after surgery, with a total of 20 cases (1.8% and 17.4%. The other common complications were: atelectasis (19 cases, 1.7% and 16.5%, pulmonary infection (18 cases, 1.6% and 15.7%, etc. The less common

  16. Enhanced performance of hybrid solar cells using longer arms of quantum cadmium selenide tetrapods

    KAUST Repository

    Lee, Kyu-Sung

    2011-12-01

    We demonstrate that enhanced device performance of hybrid solar cells based on tetrapod (TP)-shaped cadmium selenide (CdSe) nanoparticles and conjugated polymer of poly (3-hexylthiophene) (P3HT) can be obtained by using longer armed tetrapods which aids in better spatial connectivity, thus decreasing charge hopping events which lead to better charge transport. Longer tetrapods with 10 nm arm length lead to improved power conversion efficiency of 1.12% compared to 0.80% of device having 5 nm short-armed tetrapods:P3HT photoactive blends.

  17. Enhanced performance of hybrid solar cells using longer arms of quantum cadmium selenide tetrapods

    KAUST Repository

    Lee, Kyu-Sung; Kim, Inho; Gullapalli, Sravani; Wong, Michael S.; Jabbour, Ghassan E.

    2011-01-01

    We demonstrate that enhanced device performance of hybrid solar cells based on tetrapod (TP)-shaped cadmium selenide (CdSe) nanoparticles and conjugated polymer of poly (3-hexylthiophene) (P3HT) can be obtained by using longer armed tetrapods which aids in better spatial connectivity, thus decreasing charge hopping events which lead to better charge transport. Longer tetrapods with 10 nm arm length lead to improved power conversion efficiency of 1.12% compared to 0.80% of device having 5 nm short-armed tetrapods:P3HT photoactive blends.

  18. What Explains the Survival Gap of Pushed and Pulled Corporate Spin-offs?

    DEFF Research Database (Denmark)

    Rocha, Vera; Carneiro, Anabela; Varum, Celeste

    2015-01-01

    Unconditionally, pushed spin-offs are found to survive longer than their pulled counterparts. Using matched employer-employee data and novel multivariate decomposition techniques, we show that pushed spin-offs’ relative survival advantage is mostly explained by their larger human capital endowments...

  19. Changing Pattern in Malignant Mesothelioma Survival

    Directory of Open Access Journals (Sweden)

    Jennifer Faig

    2015-02-01

    Full Text Available Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal. Data are conflicting regarding the effect of asbestos exposure on mesothelioma location. OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure. METHODS: Data were analyzed from cases (n = 380 diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record. RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001 after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1 diagnosed with peritoneal mesothelioma, 2 female, 3 exposed, and 4 diagnosed at a younger age and to have a 5 shorter latency compared to occupational cases (P < .001. CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.

  20. Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity.

    Science.gov (United States)

    Bissa, Massimiliano; Quaglino, Elena; Zanotto, Carlo; Illiano, Elena; Rolih, Valeria; Pacchioni, Sole; Cavallo, Federica; De Giuli Morghen, Carlo; Radaelli, Antonia

    2016-10-01

    The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VV IHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFNγ-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VV IHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/intranasal administration routes contributed to effective immune responses and mouse survival. Copyright

  1. Action of apilite on radiosensitivity of mice

    International Nuclear Information System (INIS)

    Artemov, N.M.; Kon'kova, L.G.; Sergeyeva, L.I.

    1975-01-01

    A preparation of bee venom - apilite - has been administered to mice in different periods prior to and after the exposure to 600 and 500 r (6 and 10 μg/g, respectively). This preparation is freed from allergizating proteins and enzymes of the venom. Its basic active substance is polypeptid melittine. Apilite has been found to exert a protective effect: the survival of the experimental groups of mice is 27-44 per cent higher than that of the controls. It has also been revealed that apilite has a positive action on a number of indices of the peripheral blood of irradiated animals

  2. Food Prejudices and Survival

    Science.gov (United States)

    1955-05-01

    are the beet part of the fish. He no longer desired variety in the cooking, becsoe fond of row fish, and liked fermented whale oil. Later, he...expedition in 1845 to search for the Northwest passage, he took along a three-year supply of lime juice, vinegar , fresh carrots, onions, cranberries

  3. Radioprotective effect of RSP-CM on mice irradiated with different doses

    International Nuclear Information System (INIS)

    Zhang Xia; Yang Rujun; Zhang Xin; Yang Yunfang; Jin Zhijun; Xiang Yingsong

    2000-01-01

    Objective: To investigate the radioprotective effects of cytokines on hematopoietic impairment of irradiated mice. Methods: Using RSP-CM and LP3-CM respectively originated GM-CSF and G-CSF to treat ICR mice irradiated with different doses of 60 Co γ-rays. The 30-day survival rate of mice, the mean survival days of dead mice were determined and the numbers of peripheral white blood cells and BMC of part of the mice were counted. At the same time, GM clonogenic activity of BM was assayed. Results:RSP-CM could effectively raise 30-day survival rate of mice irradiated with 7.5 Gy. However, LP3-CM had no obvious effect. Judging from the comparative survival ratio, only the RSP-CM treated group showed protective effect on the 8.0 Gy -irradiated mice. The 8.5 Gy-irradiated mice all died within 30 days, indicating that GM-CSF had weak effect on higher dose-irradiated mice. Conclusion: GM-CSF can stimulate the hematopoietic system of irradiated mice, and has dose-effect and time-effect relations. M-CSF used singly has no obvious effect

  4. 16,16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation

    International Nuclear Information System (INIS)

    Hanson, W.R.; Thomas, C.

    1983-01-01

    A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE 2 , shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after 137 Cs gamma(γ) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE 2 was given before but not after 137 Cs γ irradiation. The maximum degree of 16,16-dimethyl PGE 2 -induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE 2 and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE 2 may in part be protected from the lethal effects of ionizing photon radiation

  5. Economic comparisons of haul road construction versus forwarding versus longer skid distances

    Science.gov (United States)

    Michael D. Erickson; Curt C. Hassler; Chris B. LeDoux

    1992-01-01

    There currently exists no set of basic guidelines for Appalachian loggers to use in the decision making process for selecting the best way to harvest a tract of timber. Specifically, guidelines are needed for deciding between the alternatives of constructing truck haul roads to access an area or other alternatives such as skidding or forwarding timber longer distances...

  6. Women live longer than men even during severe famines and epidemics

    DEFF Research Database (Denmark)

    Zarulli, Virginia; Barthold Jones, Julia A; Oksuzyan, Anna

    2018-01-01

    Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We inves...

  7. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

    NARCIS (Netherlands)

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-01-01

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might

  8. Can longer forest harvest intervals increase summer streamflow for salmon recovery?

    Science.gov (United States)

    The Mashel Streamflow Modeling Project in the Mashel River Basin, Washington, is using a watershed-scale ecohydrological model to assess whether longer forest harvest intervals can remediate summer low flow conditions that have contributed to sharply reduced runs of spawning Chin...

  9. Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects

    DEFF Research Database (Denmark)

    Barbieri, Michelangela; Paolisso, Giuseppe; Kimura, Masayuki

    2009-01-01

    Mutations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels of IGF-1 in humans are associated with aging-related diseases and diminished longevity. As leukocyte telomere length (LTL) is os...

  10. Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice.

    Science.gov (United States)

    Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling

    2016-04-01

    Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Distribution and tumour cytotoxicity of the radiosensitizer misonidazole (Ro-07-0582) in C57 mice

    International Nuclear Information System (INIS)

    Pedersen, J.E.; Smith, M.R.; Bugden, R.D.; Peckham, M.J.

    1979-01-01

    The distribution and clearance of misonidazole (MIS=Ro-07-0582) were studied in C57 mouse tissued and in transplants of Lewis lung tumour. The half life of the drug in blood after a dose of 1mg/g i.p. was 3 h. Some tissues, such as liver, were found to have consistently low MIS levels, and this was found to be due to degradation of the drug after removal of the tissues from the host. The in vivo cytotoxicity of MIS to Lewis lung tumour cells was studied using an in-vitro colony assay. After half of the tumours had been irradiated with 10 Gy to kill most of the oxic cells, the mice received i.p. injections of MIS. To simulate the longer drug exposure of human tumour cells (due to the longer half life in man) a repeated injection regime was used in some mice. There was no significant cell kill after a single dose, but with a prolonged exposure to the drug in the multiply injected animals, cell survival was reduced to 50% of control in both the irradiated and unirradiated tumours. Since the hypoxic fraction of the unirradiated tumour is probably not more than 30%, it would appear that MIS is not selectively cytotoxic to hypoxic cells. However, MIS had a much greater cytotoxic effect upon hypoxic Lewis lung tumour cells in vitro, with very little or no effect on cells grown in air. This would support the theory that the presence of hypoxic cells is essential for the expression of MIS cytotoxicity. (author)

  12. Enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 deficient mice

    International Nuclear Information System (INIS)

    Zhang Zengli; Ding Xiaofei; Tong Jian; Li Bingyan

    2011-01-01

    To investigate whether impaired osteogenesis resulting from vitamin D deficiency can influence hematopoiesis recovery after radiation, the 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) gene knockout (KO) mice and wild type (WT) mice were subjected to different doses of gamma ray. The survival rates, peripheral blood cell counts and bone marrow cellularity were studied after irradiation (IR). The survival rates of the KO mice were significantly lower than that of WT mice after 6 or 8 Gy dose of radiation. The recovery of white blood cells in KO mice was significantly delayed compared with that in WT mice after radiation. The red blood cell number in WT mice was observed to increase more than that in KO mice at days 14 and 28 after radiation. The nadir platelet count in KO mice was nearly half of that in WT mice. Dramatically higher bone marrow cell numbers were found in WT mice compared with KO mice. Our findings demonstrate the enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 (1,25-(OH) 2 D 3 ) deficient mice. (author)

  13. Disruption of the GH Receptor Gene in Adult Mice Increases Maximal Lifespan in Females

    DEFF Research Database (Denmark)

    Junnila, Riia K.; Duran-Ortiz, Silvana; Suer, Ozan

    2016-01-01

    GH and IGF-1 are important for a variety of physiological processes including growth, development, and aging. Mice with reduced levels of GH and IGF-1 have been shown to live longer than wild-type controls. Our laboratory has previously found that mice with a GH receptor gene knockout (GHRKO) fro...

  14. Factors related to resistance to hematopoietic death in mice

    International Nuclear Information System (INIS)

    Mori, Nobuko; Okumoto, Masaaki; Yonezawa, Morio; Nishikawa, Ryosuke; Takamori, Yasuhiko; Esaki, Kozaburo.

    1994-01-01

    Mouse strain difference in the radiosensitivity to hematopoietic death is thought to be determined by several factors besides radiosensitivity and the initial number of hematopoietic stem cells. Factors related to the survival of mice exposed to X-irradiation were analyzed using BALB/cHeA and STS/A strains whose LD 50/30 values differ markedly (BALB/cHeA, 5.55 Gy; STS/A, 8.45 Gy). STS/A mice exposed to 4 Gy of X-irradiation showed a small reduction but rapid recovery of blood cells (leukocytes, erythrocytes, and thrombocytes) when compared with BALB/cHeA mice. The survival of endogenous and exogenous CFU-S was much higher, by a magnitude of one log or more, in STS/A mice than those in BALB/cHeA mice; whereas the initial numbers of femoral CFU-S were similar for the two strains. The recovery of exogenous CFU-S was much more rapid in STS/A mice than it was in BALB/cHeA mice after 4 Gy of X-irradiation. Furthermore, spleen colonies produced by the transfusion of STS/A marrow cells into syngeneic recipients were significantly larger than those produced by BALB/cHeA marrow cells, regardless of whether the mice used for sources of marrow cells had been irradiated. But, there was no such difference when unirradiated marrow cells from the two strains were transfused into (BALB/cHeA X STS/A) F 1 recipients. These results indicate the possible contribution of a host factor (s) that stimulates the growth of spleen colonies after radiation to the radioresistance of STS/A mice, in addition to the primary effect of higher number of survivals of endogenous and exogenous CFU-S in STS/A mice. (author)

  15. Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

    Science.gov (United States)

    Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-02-01

    Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

  16. Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

    Science.gov (United States)

    Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-06-07

    Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

  17. Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice.

    Science.gov (United States)

    Wagner, R D; Pierson, C; Warner, T; Dohnalek, M; Farmer, J; Roberts, L; Hilty, M; Balish, E

    1997-10-01

    Four species of probiotic bacteria were assessed for their capacities to protect athymic bg/bg-nu/nu and euthymic bg/bg-nu/+ mice from mucosal and systemic candidiasis. Each bacterial species and Candida albicans colonized the gastrointestinal tracts of both strains of mice. The presence of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, or Bifidobacterium animalis) in the gastrointestinal tracts prolonged the survival of adult and neonatal bg/bg-nu/nu mice compared to that of isogenic mice colonized with C. albicans alone. The incidence of systemic candidiasis in bg/bg-nu/nu mice was significantly reduced by each of the four probiotic bacterial species. The numbers of C. albicans present in the alimentary tracts of euthymic bg/bg-nu/+ mice were significantly reduced by L. casei GG and B. animalis. None of the probiotic bacteria species completely prevented mucosal candidiasis, but B. animalis reduced its incidence and severity. Probiotic bacteria also modulated antibody- and cell-mediated immune responses to C. albicans. The prolonged survival of mice, decreased severity of mucosal and systemic candidiasis, modulation of immune responses, decreased number of C. albicans in the alimentary tract, and reduced numbers of orogastric infections demonstrated not only that probiotic bacteria have biotherapeutic potential for prophylaxis against and therapy of this fungal disease but also that probiotic bacteria protect mice from candidiasis by a variety of immunologic (thymic and extrathymic) and nonimmunologic mechanisms in this model.

  18. Working (longer than) 9 to 5: are there cardiometabolic health risks for young Australian workers who report longer than 38-h working weeks?

    Science.gov (United States)

    Reynolds, Amy C; Bucks, Romola S; Paterson, Jessica L; Ferguson, Sally A; Mori, Trevor A; McArdle, Nigel; Straker, Leon; Beilin, Lawrence J; Eastwood, Peter R

    2018-05-01

    The average Australian working week in middle-aged and older workers exceeds government recommendations. Long working weeks are associated with poor health outcomes; however, the relationship between long working weeks and health in young Australian workers is unknown. Data were drawn from the 22-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study in Perth, Western Australia. Information was available from 873 young adults about working hours per week, shift work and sleep duration. Blood samples provided measures of cardiometabolic risk (CMR) factors. Almost one-third (32.8%) of young workers reported > 38 h working weeks. This was commonly reported in mining and construction industries for males; health and social assistance, mining and retail trade industries for females. CMR factors including increased waist circumference, higher fasting plasma glucose and reduced HDL cholesterol were associated with > 38 h working weeks. These relationships were not moderated by gender or by BMI for glucose and HDL cholesterol. Total sleep time was significantly lower in both male and female workers reporting > 38 h working weeks, but did not mediate the relationships seen with CMR factors. These findings point to early associations between > 38 h working weeks and CMR risk, and highlight the potential benefit of making young employees aware of the health associations with working arrangements to reduce the longer-term relationships seen with working hours and poor cardiometabolic health in population studies.

  19. GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

    Science.gov (United States)

    Brown-Borg, Holly M; Bartke, Andrzej

    2012-06-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

  20. Multiple neoplasms, single primaries, and patient survival

    Directory of Open Access Journals (Sweden)

    Amer MH

    2014-03-01

    clinical behavior with longer survival rates, possibly related to genetic predisposition. Keywords: genetic susceptibility, incidence study, hereditary, multiple primary neoplasms, survival analysis, prognosis

  1. Surviving After Suicide

    Science.gov (United States)

    ... fewer tools for communicating their feelings. Surviving After Suicide Fact Sheet 3 Children are especially vulnerable to feelings of guilt and ... to take care of them. Secrecy about the suicide in the hopes of protecting children may cause further complications. Explain the situation and ...

  2. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  3. Education for Survival.

    Science.gov (United States)

    Allen, James E., Jr.

    In this address, James E. Allen, Jr., Assistant Secretary for Education and U.S. Commissioner of Education, discusses the relationship of education to the problem of ecological destruction. He states that the solutions to the problems of air, water, and soil pollution may be found in redirected education. This "education for survival" can serve to…

  4. Artists’ Survival Rate

    DEFF Research Database (Denmark)

    Bille, Trine; Jensen, Søren

    2017-01-01

    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  5. Ivastimul used to increase radioresistance of mice

    International Nuclear Information System (INIS)

    Rotkovska, D.; Vacek, A.; Bartonickova, A.

    1989-01-01

    A study was made of the effect of ivastimul (IS), an aqueous extract from unicellular Chlorella algae, on the radioresistance and some haemopoiesis parameters of mice exposed to 60 Co-γ-radiation. With median and absolutely lethal radiation doses, IS was shown to produce a pronounced protective effect displayed by the increased survival rate. With sublethal doses, IS elevated the postirradiation formation of endogenous colonies and restoration of bone marrow and spleen cellularity and spleen mass

  6. Novel thermal annealing methodology for permanent tuning polymer optical fiber Bragg gratings to longer wavelengths.

    Science.gov (United States)

    Pospori, A; Marques, C A F; Sagias, G; Lamela-Rivera, H; Webb, D J

    2018-01-22

    The Bragg wavelength of a polymer optical fiber Bragg grating can be permanently shifted by utilizing the thermal annealing method. In all the reported fiber annealing cases, the authors were able to tune the Bragg wavelength only to shorter wavelengths, since the polymer fiber shrinks in length during the annealing process. This article demonstrates a novel thermal annealing methodology for permanently tuning polymer optical fiber Bragg gratings to any desirable spectral position, including longer wavelengths. Stretching the polymer optical fiber during the annealing process, the period of Bragg grating, which is directly related with the Bragg wavelength, can become permanently longer. The methodology presented in this article can be used to multiplex polymer optical fiber Bragg gratings at any desirable spectral position utilizing only one phase-mask for their photo-inscription, reducing thus their fabrication cost in an industrial setting.

  7. Danish travel activities: do we travel more and longer – and to what extent?

    DEFF Research Database (Denmark)

    Knudsen, Mette Aagaard

    Two separate Danish National travel surveys are analysed to outline the amount and extent of national and international travelling during the latest 15-20 years; the national travel survey (TU) describes mainly national daily travel activities, whereas the holiday and business travel survey...... describes national and international travel activities including overnight stay(s). When sampling only respondents with trips above 100 kilometres, they only accounts for around 2% of all daily travel activities, however, this share appears to increase and suggest in general that we do travel longer....... But due to this limited share of trips, the overall impacts of longer distance travelling vanish when considering all daily travel activities. Especially as about 95% of all daily travel destinations range less than 50 kilometres away and in total induce an average trip length of 20 kilometres. If focus...

  8. Targeted treatment trials for tuberous sclerosis and autism: no longer a dream

    OpenAIRE

    Sahin, Mustafa

    2012-01-01

    Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual...

  9. Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood.

    Science.gov (United States)

    Sadauskaite-Kuehne, Vaiva; Ludvigsson, Johnny; Padaiga, Zilvinas; Jasinskiene, Edita; Samuelsson, Ulf

    2004-01-01

    Early weaning diet, early introduction of breast milk substitution and cow's milk have been shown to increase the risk of type 1 diabetes later in life. It is also shown that older maternal age, maternal education, preeclampsia, prematurity, neonatal illness and neonatal icterus caused by blood group incompatibility, infections and stress might be risk factors for type 1 diabetes. We aimed to determine whether early nutrition is an independent risk factor for diabetes despite other life events. Data from 517 children (268 boys and 249 girls) in south-east of Sweden and 286 children (133 boys and 153 girls) in Lithuania in the age group of 0 to 15 years with newly diagnosed type 1 diabetes mellitus were included into analysis. Three age- and sex-matched healthy controls were randomly selected. Response rate in control families in Sweden was 72.9% and in Lithuania 94.8%. Information was collected via questionnaires. Exclusive breastfeeding longer than five months (odds ratio 0.54, 95% confidence interval 0.36-0.81) and total breastfeeding longer than 7 (0.56, 0.38-0.84) or 9 months (0.61, 0.38-0.84), breastfeeding substitution that started later than the third month (0.57, 0.33-0.98) among Swedish children 5 to 9 years old and later than the seventh month (0.24, 0.07-0.84) among all Swedish children is protective against diabetes when adjusted for all other above-listed risk factors. In Lithuania, exclusive breastfeeding longer than two months in the age group of 5 to 9 years is protective (0.58, 0.34-0.99) when adjusted for other factors. Longer exclusive and total breastfeeding appears as an independent protective factor against type 1 diabetes. Copyright 2004 John Wiley & Sons, Ltd.

  10. Ghrelin reverses experimental diabetic neuropathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  11. Ghrelin reverses experimental diabetic neuropathy in mice

    International Nuclear Information System (INIS)

    Kyoraku, Itaru; Shiomi, Kazutaka; Kangawa, Kenji; Nakazato, Masamitsu

    2009-01-01

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin α, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  12. Processing of semen by density gradient centrifugation selects spermatozoa with longer telomeres for assisted reproduction techniques.

    Science.gov (United States)

    Yang, Qingling; Zhang, Nan; Zhao, Feifei; Zhao, Wanli; Dai, Shanjun; Liu, Jinhao; Bukhari, Ihtisham; Xin, Hang; Niu, Wenbing; Sun, Yingpu

    2015-07-01

    The ends of eukaryotic chromosomes contain specialized chromatin structures called telomeres, the length of which plays a key role in early human embryonic development. Although the effect of sperm preparation techniques on major sperm characteristics, such as concentration, motility and morphology have been previously documented, the possible status of telomere length and its relation with sperm preparation techniques is not well-known for humans. The aim of this study was to investigate the role of density gradient centrifugation in the selection of spermatozoa with longer telomeres for use in assisted reproduction techniques in 105 samples before and after sperm processing. After density gradient centrifugation, the average telomere length of the sperm was significantly longer (6.51 ± 2.54 versus 5.16 ± 2.29, P average motile sperm rate was significantly higher (77.9 ± 11.8 versus 44.6 ± 11.2, P average DNA fragmentation rate was significantly lower (11.1 ± 5.9 versus 25.9 ± 12.9, P sperm count (rs = 0.58; P sperm with longer telomeres. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  13. Sexual selection on receptor organ traits: younger females attract males with longer antennae

    Science.gov (United States)

    Johnson, Tamara L.; Symonds, Matthew R. E.; Elgar, Mark A.

    2017-06-01

    Sexual selection theory predicts that female choice may favour the evolution of elaborate male signals. Darwin also suggested that sexual selection can favour elaborate receiver structures in order to better detect sexual signals, an idea that has been largely ignored. We evaluated this unorthodox perspective by documenting the antennal lengths of male Uraba lugens Walker (Lepidoptera: Nolidae) moths that were attracted to experimentally manipulated emissions of female sex pheromone. Either one or two females were placed in field traps for the duration of their adult lives in order to create differences in the quantity of pheromone emissions from the traps. The mean antennal length of males attracted to field traps baited with a single female was longer than that of males attracted to traps baited with two females, a pattern consistent with Darwin's prediction assuming the latter emits higher pheromone concentrations. Furthermore, younger females attracted males with longer antennae, which may reflect age-specific changes in pheromone emission. These field experiments provide the first direct evidence of an unappreciated role for sexual selection in the evolution of sexual dimorphism in moth antennae and raise the intriguing possibility that females select males with longer antennae through strategic emission of pheromones.

  14. LPI Thresholds in Longer Scale Length Plasmas Driven by the Nike Laser*

    Science.gov (United States)

    Weaver, J.; Oh, J.; Phillips, L.; Afeyan, B.; Seely, J.; Kehne, D.; Brown, C.; Obenschain, S.; Serlin, V.; Schmitt, A. J.; Feldman, U.; Holland, G.; Lehmberg, R. H.; McLean, E.; Manka, C.

    2010-11-01

    The Krypton-Fluoride (KrF) laser is an attractive driver for inertial confinement fusion due to its short wavelength (248nm), large bandwidth (1-3 THz), and beam smoothing by induced spatial incoherence. Experiments with the Nike KrF laser have demonstrated intensity thresholds for laser plasma instabilities (LPI) higher than reported for other high power lasers operating at longer wavelengths (>=351 nm). The previous Nike experiments used short pulses (350 ps FWHM) and small spots (<260 μm FWHM) that created short density scale length plasmas (Ln˜50-70 μm) from planar CH targets and demonstrated the onset of two-plasmon decay (2φp) at laser intensities ˜2x10^15 W/cm^2. This talk will present an overview of the current campaign that uses longer pulses (0.5-4.0 ns) to achieve greater density scale lengths (Ln˜100-200 μm). X-rays, emission near ^1/2φo and ^3/2φo harmonics, and reflected laser light have been monitored for onset of 2φp. The longer density scale lengths will allow better comparison to results from other laser facilities. *Work supported by DoE/NNSA and ONR.

  15. Avalanching Systems with Longer Range Connectivity: Occurrence of a Crossover Phenomenon and Multifractal Finite Size Scaling

    Directory of Open Access Journals (Sweden)

    Simone Benella

    2017-07-01

    Full Text Available Many out-of-equilibrium systems respond to external driving with nonlinear and self-similar dynamics. This near scale-invariant behavior of relaxation events has been modeled through sand pile cellular automata. However, a common feature of these models is the assumption of a local connectivity, while in many real systems, we have evidence for longer range connectivity and a complex topology of the interacting structures. Here, we investigate the role that longer range connectivity might play in near scale-invariant systems, by analyzing the results of a sand pile cellular automaton model on a Newman–Watts network. The analysis clearly indicates the occurrence of a crossover phenomenon in the statistics of the relaxation events as a function of the percentage of longer range links and the breaking of the simple Finite Size Scaling (FSS. The more complex nature of the dynamics in the presence of long-range connectivity is investigated in terms of multi-scaling features and analyzed by the Rank-Ordered Multifractal Analysis (ROMA.

  16. On the influence of ultraviolet radiation on spontaneous tumors in NMRI mice

    International Nuclear Information System (INIS)

    Koenigsmann, G.; Kinkel, H.J.; Bocionek, P.; Wolff, F.

    1981-01-01

    During a period of 12 and 15 months respectively, female NMRI mice were irradiated twelve hours per day with specific parts of the ultraviolet spectrum (three groups, each comprising 100 animals: non-irradiated control group, animals irradiated with B units, animals irradiated with A/B units). No considerable influence of the chronic exposure to ultraviolet radiation could be demonstrated with regard to the development of the body weight and the hematologic condition. Group B had the same rate of spontaneous tumors of the respiratory tract as the control group; this rate was higher in group A/B. As to the development of spontaneous tumors in the lymphatic tissues, there seems to be a dependence on radiation: the animals of group B presented a slightly higher, those of group A/B a higher development than the animals of the nonirradiated control group. It cannot be definitely clarified yet to what extent this increased tumor rate was additionally induced by the higher environmental temperature or other influences involved by experiment. Harding-Passey melanomas were inoculated in NMRI mice and, 48 hours later, they were exposed to defined emission spectra within the natural ultraviolet spectrum. The exposed animals showed a slower growth of the transplanted tumors than the non-exposed animals, and especially the animals exposed to UVB radiation had a longer survival time. This chronic irradiation test was carried out in order to examine the influence of defined emission spectra on autochthonous tumors in NMRI mice and on their spontaneous tumor rate and blood count. (orig.) [de

  17. Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

    Science.gov (United States)

    Helmi, Nawal; Andrew, Peter W; Pandya, Hitesh C

    2015-05-15

    Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Do longer consultations improve the management of psychological problems in general practice? A systematic literature review

    Directory of Open Access Journals (Sweden)

    Hutton Catherine

    2007-05-01

    Full Text Available Abstract Background Psychological problems present a huge burden of illness in our community and GPs are the main providers of care. There is evidence that longer consultations in general practice are associated with improved quality of care; but this needs to be balanced against the fact that doctor time is a limited resource and longer consultations may lead to reduced access to health care. The aim of this research was to conduct a systematic literature review to determine whether management of psychological problems in general practice is associated with an increased consultation length and to explore whether longer consultations are associated with better health outcomes for patients with psychological problems. Methods A search was conducted on Medline (Ovid databases up to7 June 2006. The following search terms, were used: general practice or primary health care (free text or family practice (MeSH AND consultation length or duration (free text or time factors (MeSH AND depression or psychological problems or depressed (free text. A similar search was done in Web of Science, Pubmed, Google Scholar, and Cochrane Library and no other papers were found. Studies were included if they contained data comparing consultation length and management or detection of psychological problems in a general practice or primary health care setting. The studies were read and categories developed to enable systematic data extraction and synthesis. Results 29 papers met the inclusion criteria. Consultations with a recorded diagnosis of a psychological problem were reported to be longer than those with no recorded psychological diagnosis. It is not clear if this is related to the extra time or the consultation style. GPs reported that time pressure is a major barrier to treating depression. There was some evidence that increased consultation length is associated with more accurate diagnosis of psychological problems. Conclusion Further research is needed to

  19. Study of compatibility of oligo-chitosan and ginkgo bilobal polyprenol influences on micronuclear rates and p53, gadd45 protein expression of radiated mice

    International Nuclear Information System (INIS)

    Guo Jianping; Wang Yongli; Wei Jinping; Yang Zhongtian; Liu Chunhui

    2012-01-01

    Study of compatibility of oligo-chitosan and ginkgo bilobal polyprenol (GP) influences on micronuclear rate and p53, gadd45 protein expression of radiated mice. Survival rate and survival time of 30-day-time of radiated mice was studied with the mixture of compatibility of oligo-chitosan and different density of GP. High survival rate of mixture density was screening. Another study on this mixture density was about micronuclear rates of marrow and p53, gadd45 protein of spleen after mice were radiated 12 h. The mixture of 300 mg/kg oligo-chitosan and 5 mg/kg GP could increase remarkably the survival rate and survival time of 30-day-time of radiated mice and degrade micronuclear rates and p53, gadd45 protein expression. Compatibility of oligo-chitosan and GP effectively raise the survival rate of radiated mice. It could proved initially that the mixture has the function of radiation protection. (authors)

  20. Radiobilogical cell survival models

    International Nuclear Information System (INIS)

    Zackrisson, B.

    1992-01-01

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose-response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowlegde of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell surivival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level. (orig.)

  1. Carbonaceous Survivability on Impact

    Science.gov (United States)

    Bunch, T. E.; Becker, Luann; Morrison, David (Technical Monitor)

    1994-01-01

    In order to gain knowledge about the potential contributions of comets and cosmic dust to the origin of life on Earth, we need to explore the survivability of their potential organic compounds on impact and the formation of secondary products that may have arisen from the chaotic events sustained by the carriers as they fell to Earth. We have performed a series of hypervelocity impact experiments using carbon-bearing impactors (diamond, graphite, kerogens, PAH crystals, and Murchison and Nogoya meteorites) into Al plate targets at velocities - 6 km/s. Estimated peak shock pressures probably did not exceed 120 GPa and peak shock temperatures were probably less than 4000 K for times of nano- to microsecs. Nominal crater dia. are less than one mm. The most significant results of these experiments are the preservation of the higher mass PAHs (e. g., pyrene relative to napthalene) and the formation of additional alkylated PAHs. We have also examined the residues of polystyrene projectiles impacted by a microparticle accelerator into targets at velocities up to 15 km/s. This talk will discuss the results of these experiments and their implications with respect to the survival of carbonaceous deliverables to early Earth. The prospects of survivability of organic molecules on "intact" capture of cosmic dust in space via soft: and hard cosmic dust collectors will also be discussed.

  2. Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

    Science.gov (United States)

    Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

    2013-01-01

    We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

  3. Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

    Directory of Open Access Journals (Sweden)

    Saki Imai

    Full Text Available We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92, and mice with this mutation (MT mice, as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

  4. Radioprotective effects of bacterial superoxide dismutase on mice

    International Nuclear Information System (INIS)

    Hu Tianxi

    1992-01-01

    The radioprotective effects of bacterial superoxide dismutase (b-SOD) on the mice irradiated by 8 Gy γ-ray were investigated. The results showed that when b-SOD was injected before and after irradiation, the survival fraction of mice is increased 50% and 30% respectively. The former treatment could increase the DNA synthesis of the myeloid cells and spleen's lymphocytes, decrease the LPO of tissue homogenates and the hemolysis of erythrocytes significantly. The mechanism that b-SOD can drop the radiation injury of the mice was discussed

  5. Survival analysis models and applications

    CERN Document Server

    Liu, Xian

    2012-01-01

    Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

  6. Smelling themselves: Dogs investigate their own odours longer when modified in an "olfactory mirror" test.

    Science.gov (United States)

    Horowitz, Alexandra

    2017-10-01

    While domestic dogs, Canis familiaris, have been found to be skillful at social cognitive tasks and even some meta-cognitive tasks, they have not passed the test of mirror self-recognition (MSR). Acknowledging the motivational and sensory challenges that might hinder performance, even before the question of self-recognition is broached, this study creates and enacts a novel design extrapolated from the species' natural behaviour. Given dogs' use of olfactory signals in communication, this experiment presents dogs with various canisters for approach and investigation. Each holds an odorous stimulus: in the critical test, either an "olfactory mirror" of the subject - the dog's own urine - or one in which the odour stimulus is modified. By looking at subjects' investigation times of each canister, it is shown that dogs distinguish between the olfactory "image" of themselves when modified: investigating their own odour for longer when it had an additional odour accompanying it than when it did not. Such behaviour implies a recognition of the odour as being of or from "themselves." The ecological validity of this odour presentation is examined by presenting to the subjects odours of other known or unknown dogs: dogs spend longer investigating the odour of other dogs than their own odour. Finally, in a second experiment, subjects spent longer with the modified stimulus than with the modified odour by itself, indicating that novelty alone does not explain the dogs' behavior. This study translates the MSR study for a species whose primary sensory modality is olfaction, and finds both that natural sniffing behaviour can be replicated in the lab and that dogs show more investigative interest in their own odours when modified. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Working Less and Living Longer: Long-Term Trends in Working Time and Time Budgets

    OpenAIRE

    Ausubel, J.H.; Grubler, A.

    1994-01-01

    Analyses of time series data beginning in the mid-nineteenth century in the industrialized nations, especially in the United Kingdom, show that on average people are working significantly less while living longer. Although the average career length has remained around 40 years, the total lifetime hours worked shrank for an average British worker from 124,000 hours in 1856 to 69,000 in 1981. The fraction of disposable lifetime hours spent working declined from 50% to 20%. The female share of c...

  8. Extending 3D near-cloud corrections from shorter to longer wavelengths

    International Nuclear Information System (INIS)

    Marshak, Alexander; Evans, K. Frank; Várnai, Tamás; Wen, Guoyong

    2014-01-01

    Satellite observations have shown a positive correlation between cloud amount and aerosol optical thickness (AOT) that can be explained by the humidification of aerosols near clouds, and/or by cloud contamination by sub-pixel size clouds and the cloud adjacency effect. The last effect may substantially increase reflected radiation in cloud-free columns, leading to overestimates in the retrieved AOT. For clear-sky areas near boundary layer clouds the main contribution to the enhancement of clear sky reflectance at shorter wavelengths comes from the radiation scattered into clear areas by clouds and then scattered to the sensor by air molecules. Because of the wavelength dependence of air molecule scattering, this process leads to a larger reflectance increase at shorter wavelengths, and can be corrected using a simple two-layer model [18]. However, correcting only for molecular scattering skews spectral properties of the retrieved AOT. Kassianov and Ovtchinnikov [9] proposed a technique that uses spectral reflectance ratios to retrieve AOT in the vicinity of clouds; they assumed that the cloud adjacency effect influences the spectral ratio between reflectances at two wavelengths less than it influences the reflectances themselves. This paper combines the two approaches: It assumes that the 3D correction for the shortest wavelength is known with some uncertainties, and then it estimates the 3D correction for longer wavelengths using a modified ratio method. The new approach is tested with 3D radiances simulated for 26 cumulus fields from Large-Eddy Simulations, supplemented with 40 aerosol profiles. The results showed that (i) for a variety of cumulus cloud scenes and aerosol profiles over ocean the 3D correction due to cloud adjacency effect can be extended from shorter to longer wavelengths and (ii) the 3D corrections for longer wavelengths are not very sensitive to unbiased random uncertainties in the 3D corrections at shorter wavelengths. - Highlights:

  9. Economic impact of longer battery life of cardiac resynchronization therapy defibrillators in Sweden

    Directory of Open Access Journals (Sweden)

    Gadler F

    2016-10-01

    Full Text Available Fredrik Gadler,1 Yao Ding,2 Nathalie Verin,3 Martin Bergius,4 Jeffrey D Miller,5 Gregory M Lenhart,5 Mason W Russell5 1Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden; 2Truven Health Analytics, an IBM Company, Bethesda, MD, USA; 3Boston Scientific Corporation, Hemel Hempstead, Hertfordshire, UK; 4Boston Scientific Nordic AB, Helsingborg, Sweden; 5Truven Health Analytics, an IBM Company, Cambridge, MA, USA Objective: The objective of this study was to quantify the impact that longer battery life of cardiac resynchronization therapy defibrillator (CRT-D devices has on reducing the number of device replacements and associated costs of these replacements from a Swedish health care system perspective.Methods: An economic model based on real-world published data was developed to estimate cost savings and avoided device replacements for CRT-Ds with longer battery life compared with devices with industry-standard battery life expectancy. Base-case comparisons were performed among CRT-Ds of three manufacturers – Boston Scientific Corporation, St. Jude Medical, and Medtronic – over a 6-year time horizon, as per the available clinical data. As a sensitivity analysis, we evaluated CRT-Ds as well as single-chamber implantable cardioverter defibrillator (ICD-VR and dual-chamber implantable cardioverter defibrillator (ICD-DR devices over a longer 10-year period. All costs were in 2015 Swedish Krona (SEK discounted at 3% per annum.Results: Base-case analysis results show that up to 603 replacements and up to SEK 60.4 million cumulative-associated costs could be avoided over 6 years by using devices with extended ­battery life. The pattern of savings over time suggests that savings are modest initially but increase rapidly beginning in the third year of follow-up with each year’s cumulative savings two to three times the previous year. Evaluating CRT-D, ICD-VR, and ICD-DR devices together over a longer 10-year period, the

  10. Are translations longer than source texts? A corpus-based study of explicitation

    OpenAIRE

    Frankenberg-Garcia, A

    2009-01-01

    Explicitation is the process of rendering information which is only implicit in the source text explicit in the target text, and is believed to be one of the universals of translation (Blum-Kulka 1986, Olohan and Baker 2000, Øverås 1998, Séguinot 1988, Vanderauwera 1985). The present study uses corpus technology to attempt to shed some light on the complex relationship between translation, text length and explicitation. An awareness of what makes translations longer (or shorter) and more expl...

  11. Remarkable Stability of Myelinating Oligodendrocytes in Mice

    Directory of Open Access Journals (Sweden)

    Richa B. Tripathi

    2017-10-01

    Full Text Available New myelin-forming oligodendrocytes (OLs are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover. To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months and motor cortex (∼70% survival than in corticospinal tract or optic nerve (50%–60% survival. Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year.

  12. Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

    International Nuclear Information System (INIS)

    Silva, Andreia dos Santos

    2006-01-01

    The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

  13. Survival and its predictors from age 75 to 85 in men and women belonging to cohorts with marked survival differences to age 75

    DEFF Research Database (Denmark)

    Heikkinen, E; Kauppinen, M; Schroll, M

    2016-01-01

    focusing on different domains of health, functional capacity, and physical and social activities. RESULTS: The proportion of survivors to age 75 was markedly smaller among the Finnish men and women than Danish or Swedish subjects. In the local population no marked differences in survival from age 75 to 85...... among three local Nordic populations using survival data on national cohorts as background information. METHODS: The data were derived from national registers and from samples of 75-year old living in Denmark, Sweden, and Finland. The subjects were invited to take part in interviews and examinations...... were observed between the groups of men, while women survived longer than men and longer in Göteborg than in Glostrup or Jyväskylä. Univariate models revealed 12 predictors of survival. In the multivariate models, the significant predictors among men related to physical fitness, whereas among women...

  14. An interspecies comparison of responses of mice and dogs to continuous 60Co γ irradiation

    International Nuclear Information System (INIS)

    Norris, W.P.; Tyler, S.A.; Sacher, G.A.

    1976-01-01

    Young-adult purebred beagle dogs were exposed continuously, 22h/d, to 60 Co γ rays until they died. The daily dose rates ranged from 3.5 to 210 rad. At 3.5 rad/d the mean survival time was in excess of 1860 days (the study was still in progress in Nov.1975), while at 210 rad/d mean survival time was 13 days. The data are compared with those from previously published information from similarly irradiated mice. The comparison is made in terms of radiation-specific death rate, defined as 1/MASsub(i)-1/MASsub(c), where MASsub(i) and MASsub(c) are the mean after-survival times of the irradiated and control populations, respectively. In both species, when log radiation-specific death rate is plotted against log dose rate, the response has a slope=2, i.e. the death rate increases with the square of dose rate. This occurs over the entire dose rate range where damage to haematopoietic tissues is the primary cause of death. In the mouse, at daily dose rates below 20 rad/d, haematopoietic injury is no longer a primary cause of death and the response curve shifts to slope=1 where injury is dependent only on total accumulated dose and is independent of dose rate. The data available so far suggest that a similar inflection may occur with the dog at dose rates below 3.5 rad/d. An experiment is being initiated to determine whether this will be the case. Statistical considerations, essential to the design of the study, are presented. (author)

  15. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

    Science.gov (United States)

    Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

    2016-10-27

    Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

  16. Applied survival analysis using R

    CERN Document Server

    Moore, Dirk F

    2016-01-01

    Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

  17. Why does picture naming take longer than word reading? The contribution of articulatory processes.

    Science.gov (United States)

    Riès, Stéphanie; Legou, Thierry; Burle, Borís; Alario, F-Xavier; Malfait, Nicole

    2012-10-01

    Since the 19th century, it has been known that response latencies are longer for naming pictures than for reading words aloud. While several interpretations have been proposed, a common general assumption is that this difference stems from cognitive word-selection processes and not from articulatory processes. Here we show that, contrary to this widely accepted view, articulatory processes are also affected by the task performed. To demonstrate this, we used a procedure that to our knowledge had never been used in research on language processing: response-latency fractionating. Along with vocal onsets, we recorded the electromyographic (EMG) activity of facial muscles while participants named pictures or read words aloud. On the basis of these measures, we were able to fractionate the verbal response latencies into two types of time intervals: premotor times (from stimulus presentation to EMG onset), mostly reflecting cognitive processes, and motor times (from EMG onset to vocal onset), related to motor execution processes. We showed that premotor and motor times are both longer in picture naming than in reading, although than in reading, although articulation is already initiated in the latter measure. Future studies based on this new approach should bring valuable clues for a better understanding of the relation between the cognitive and motor processes involved in speech production.

  18. A longer climate memory carried by soil freeze–thaw processes in Siberia

    International Nuclear Information System (INIS)

    Matsumura, Shinji; Yamazaki, Koji

    2012-01-01

    The climate memory of a land surface generally persists for only a few months, but analysis of surface meteorological data revealed a longer-term climate memory carried by soil freeze–thaw processes in Siberia. Surface temperature variability during the snowmelt season corresponds reasonably well with that in the summer of the following year, when most stations show a secondary autocorrelation peak. The surface temperature memory is thought to be stored as variations in the amount of snowmelt water held in the soil, and through soil freezing, which emerges as latent heat variations in the near-surface atmosphere during soil thawing approximately one year later. The ground conditions are dry in the longer-term climate memory regions, such as eastern Siberia, where less snow cover (higher surface air temperature) in spring results in less snowmelt water or lower soil moisture in the summer. Consequently, through soil freezing, it will require less latent heat to thaw in the summer of the following year, resulting in higher surface air temperature. In addition to soil moisture and snow cover, soil freeze–thaw processes can also act as agents of climate memory in the near-surface atmosphere. (letter)

  19. Hyaluronic Acid Injections in Medicare Knee Osteoarthritis Patients Are Associated With Longer Time to Knee Arthroplasty.

    Science.gov (United States)

    Ong, Kevin L; Anderson, Allen F; Niazi, Faizan; Fierlinger, Anke L; Kurtz, Steven M; Altman, Roy D

    2016-08-01

    Few nonoperative treatment options for knee osteoarthritis (OA) are available, but there is ongoing debate about the effectiveness of intra-articular (IA) hyaluronic acid (HA) injections. We investigated whether the formulation of IA HA, or its combined use with IA corticosteroid (CS), may be contributing to some of the reported variation in clinical outcomes. The 5% Part B Medicare data (2005-2012) were used to identify knee OA patients who underwent knee arthroplasty (KA). The time from diagnosis of OA to KA was compared between patients with (HA) and without (no HA) IA HA use, using quantile regression with propensity score adjustment. These were further stratified by type of IA HA. Patient factors associated with time to KA were also assessed using Cox regression. The "HA" cohort was associated with a longer time to KA of 8.7 months (95% confidence interval: 8.3-9.1 months; P injection use. Patients with both IA HA and IA CS had an additional 6.3 months (95% confidence interval: 5.5-7.0 months; P < .001) to KA over those with only IA HA. In a large cohort of elderly patients undergoing KA, there was a significant longer time from diagnosis of OA to KA in those receiving IA HA. It is unclear if the extended time may lead to less KA utilization. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births

    Directory of Open Access Journals (Sweden)

    S. J. Kroese

    2017-01-01

    Full Text Available Objective. To investigate the effect of hydroxychloroquine (HCQ in pregnant women with systemic lupus erythematosus (SLE. Methods. In SLE pregnancies of a single Dutch center (2000–2015, lupus activity and flares before and during pregnancy and postpartum were assessed using the SLE Disease Activity Index (SLEDAI/SLEPDAI (SLEDAI adjusted for pregnancy. The association between HCQ use and pregnancy outcomes (early spontaneous abortion, fetal death, and preterm and term live birth was analyzed using generalized estimating equations (GEE accounting for the occurrence of multiple pregnancies per patient. Analyses were adjusted for antiphospholipid antibody (aPL status. Results. 110 pregnancies (63 mostly Caucasian patients were included, of which, in 30, HCQ was used; overall occurrence of flares was low (non-HCQ group: 5 mild (6.4% and 2 severe (2.6%; HCQ group: 2 mild (6.7% and no severe flares. The HCQ group showed a trend towards lower dosage of prednisone (OR 0.2 (95% CI 0.0–1.4; p=0.10. Pregnancy outcomes were comparable between groups. Among preterm live births, pregnancy duration was significantly longer in HCQ users (2.4 weeks (95% CI 1.0–3.8; p≤0.001. Conclusion. HCQ use was associated with longer pregnancy duration in the vulnerable preterm birth population, underscoring the beneficial effect of HCQ use during pregnancy.

  1. Prospective Memory Deficits in Ecstasy Users: Effects of Longer Ongoing Task Delay Interval

    Science.gov (United States)

    WEINBORN, MICHAEL; WOODS, STEVEN PAUL; NULSEN, CLAIRE; PARK, KATHERINE

    2011-01-01

    Ecstasy use has been associated with neurotoxicity and neurocognitive impairment in a variety of domains, including prospective memory (ProM), which involves the delayed execution of a previously encoded intention in response to a specific cue. The present study adopted the multiprocess theory of ProM to evaluate the hypothesis that ecstasy users would evidence differentially impaired ProM on longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk alcohol users (n = 21) and healthy nonusers (n = 31) completed the short (2-min) and long (15-min) delay ProM scales of the Memory for Intentions Screening Test. Results showed a significant group by ProM delay interaction, such that ecstasy users performed comparably to the comparison groups on short-delay trials, but were impaired on long-delay ProM, particularly for time-based cues. Among the ecstasy users, long-delay ProM was positively associated with risky decision-making, but not with retrospective memory or other aspects of executive functions. These findings suggest that ecstasy users may be particularly susceptible to deficits in strategic target monitoring and maintenance of cue-intention pairings over longer ProM delays. Findings are discussed in the context of their potential everyday functioning (e.g., academic, vocational) and treatment implications for ecstasy users. PMID:22047194

  2. Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

    OpenAIRE

    Latimer, N.R.; White, I.R.; Abrams, K.R.; Sieburt, U.

    2017-01-01

    Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when e...

  3. The regenerative potential of parietal epithelial cells in adult mice.

    Science.gov (United States)

    Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J

    2014-04-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman's capsule expressed podocyte markers, and cells on Bowman's capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman's capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman's capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman's capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans.

  4. Lovastatin protects against experimental plague in mice.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

  5. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  6. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  7. Reduced SHARPIN and LUBAC Formation May Contribute to CCl4- or Acetaminophen-Induced Liver Cirrhosis in Mice

    Directory of Open Access Journals (Sweden)

    Takeshi Yamamotoya

    2017-02-01

    Full Text Available Linear ubiquitin chain assembly complex (LUBAC, composed of SHARPIN (SHANK-associated RH domain-interacting protein, HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1, and HOIP (HOIL-1L interacting protein, forms linear ubiquitin on nuclear factor-κB (NF-κB essential modulator (NEMO and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl4 or acetaminophen (APAP, both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity.

  8. Survival curves for irradiated cells

    International Nuclear Information System (INIS)

    Gibson, D.K.

    1975-01-01

    The subject of the lecture is the probability of survival of biological cells which have been subjected to ionising radiation. The basic mathematical theories of cell survival as a function of radiation dose are developed. A brief comparison with observed survival curves is made. (author)

  9. Electric shocks are ineffective in treatment of lethal effects of rattlesnake envenomation in mice.

    Science.gov (United States)

    Johnson, E K; Kardong, K V; Mackessy, S P

    1987-01-01

    Electrical shocks, even crudely delivered from 'stun guns' and gasoline engine spark plugs, have been reported to be effective in the treatment of snake bite. We thus applied similar electric shocks to mice artificially injected with reconstituted rattlesnake venom at various LD50 multiples. Those envenomated mice treated with electric shock survived no better than the controls. We thus found no evidence that electric shocks crudely administered had any life saving effect in mice.

  10. The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc Min/+ mice.

    Science.gov (United States)

    Ono, Junya; Shime, Hiroaki; Takaki, Hiromi; Takashima, Ken; Funami, Kenji; Yoshida, Sumito; Takeda, Yohei; Matsumoto, Misako; Kasahara, Masanori; Seya, Tsukasa

    2017-10-17

    Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in Apc Min/+ mice. Microbiota also contains double-stranded RNA (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor molecule 1 (TICAM-1, also known as TRIF) pathway. We established Apc Min/+ Ticam1 -/- mice and their survival was compared to survival of Apc Min/+ Myd88 -/- and wild-type (WT) mice. The properties of polyps were investigated using immunofluorescence staining and RT-PCR analysis. We demonstrate that TICAM-1 is essential for suppression of polyp formation in Apc Min/+ mice. TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice with knockout of MyD88 in the Apc Min/+ background. Polyps were more frequently formed in the distal intestine of Apc Min/+ Ticam1 -/- mice than in Apc Min/+ mice. Infiltration of immune cells such as CD11b + and CD8α + cells into the polyps was detected histologically. CD11b and CD8α mRNAs were increased in polyps of Apc Min/+ Ticam1 -/- mice compared to Apc Min/+ mice. Gene expression of inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, CXCL9 and IL-12p40 was increased in polyps of Apc Min/+ Ticam1 -/- mice. mRNA and protein expression of c-Myc, a critical transcription factor for inflammation-associated polyposis, were increased in polyps of Apc Min/+ Ticam1 -/- mice. A Lactobacillus strain producing dsRNA was detected in feces of Apc Min/+ mice. These results imply that the TLR3/TICAM-1 pathway inhibits polyposis through suppression of c-Myc expression and supports long survival in Apc Min/+ mice.

  11. Succession and survival in psychotherapy organizations.

    Science.gov (United States)

    Khaleelee, Olya

    2008-11-01

    This paper examines the world of psychotherapy by applying a systemic and psychodynamic understanding of the family business as a way of understanding the dilemmas and challenges of leadership succession. Oedipal factors are explored as an important theme within the succession process. This exploration is set within the context of what function psychotherapy has performed in society over the last thirty years. The hypothesis is that the first generation of leaders aimed to provide containment for the individual citizen at a time of failed dependency in society. The suggestion is that this gave way to the primary task for the second generation, which has been to focus on the therapist in training. The challenge for the third generation is to develop a meaningful role for psychotherapy today and to ensure survival at a time when other shorter therapies such as CBT are gaining ascendancy over longer term psychoanalytic psychotherapy.

  12. The rural pipeline to longer-term rural practice: General practitioners and specialists.

    Directory of Open Access Journals (Sweden)

    Marcella M S Kwan

    Full Text Available Rural medical workforce shortage contributes to health disadvantage experienced by rural communities worldwide. This study aimed to determine the regional results of an Australian Government sponsored national program to enhance the Australian rural medical workforce by recruiting rural background students and establishing rural clinical schools (RCS. In particular, we wished to determine predictors of graduates' longer-term rural practice and whether the predictors differ between general practitioners (GPs and specialists.A cross-sectional cohort study, conducted in 2012, of 729 medical graduates of The University of Queensland 2002-2011. The outcome of interest was primary place of graduates' practice categorised as rural for at least 50% of time since graduation ('Longer-term Rural Practice', LTRP among GPs and medical specialists. The main exposures were rural background (RB or metropolitan background (MB, and attendance at a metropolitan clinical school (MCS or the Rural Clinical School for one year (RCS-1 or two years (RCS-2.Independent predictors of LTRP (odds ratio [95% confidence interval] were RB (2.10 [1.37-3.20], RCS-1 (2.85 [1.77-4.58], RCS-2 (5.38 [3.15-9.20], GP (3.40 [2.13-5.43], and bonded scholarship (2.11 [1.19-3.76]. Compared to being single, having a metropolitan background partner was a negative predictor (0.34 [0.21-0.57]. The effects of RB and RCS were additive-compared to MB and MCS (Reference group: RB and RCS-1 (6.58[3.32-13.04], RB and RCS-2 (10.36[4.89-21.93]. Although specialists were less likely than GPs to be in LTRP, the pattern of the effects of rural exposures was similar, although some significant differences in the effects of the duration of RCS attendance, bonded scholarships and partner's background were apparent.Among both specialists and GPs, rural background and rural clinical school attendance are independent, duration-dependent, and additive, predictors of longer-term rural practice. Metropolitan

  13. Obesity Is Associated With More Complications and Longer Hospital Stays After Orthopaedic Trauma.

    Science.gov (United States)

    Childs, Benjamin R; Nahm, Nickolas J; Dolenc, Andrea J; Vallier, Heather A

    2015-11-01

    The objective of this study was to characterize relationships between obesity and initial hospital stay, including complications, in patients with multiple system trauma and surgically treated fractures. Prospective, observational. Level 1 trauma center. Three hundred seventy-six patients with an Injury Severity Score greater than 16 and mechanically unstable high-energy fractures of the femur, pelvic ring, acetabulum, or spine requiring stabilization. Data for obese (body mass index ≥ 30) versus nonobese patients included presence of pneumonia, deep vein thrombosis, pulmonary embolism, infection, organ failure, and mortality. Days in ICU and hospital, days on ventilator, transfusions, and surgical details were documented. Complications occurred more often in obese patients (38.0% vs. 28.4%, P = 0.03), with more acute renal failure (5.70% vs. 1.38%, P = 0.02) and infection (11.4% vs. 5.50%, P = 0.04). Days in ICU and mechanical ventilation times were longer for obese patients (7.06 vs. 5.25 days, P = 0.05 and 4.92 vs. 2.90 days, P = 0.007, respectively). Mean total hospital stay was also longer for obese patients (12.3 vs. 9.79 days, P = 0.009). No significant differences in rates of mortality, multiple organ failure, or pulmonary complications were noted. Medically stable obese patients were almost twice as likely to experience delayed fracture fixation due to preference of the surgeon and were more likely to experience delay overall (26.0% vs. 16.1%; P = 0.02). Mean time from injury to fixation was 34.9 hours in obese patients versus 23.7 hours in nonobese patients (P = 0.03). Obesity was noted among 42% of our trauma patients. In obese patients, complications occurred more often and hospital and ICU stays were significantly longer. These increases are likely to be associated with greater hospital costs. Surgeon decision to delay procedures in medically stable obese patients may have contributed to these findings; definitive fixation was more likely to be

  14. Testing, Modeling, and Monitoring to Enable Simpler, Cheaper, Longer-lived Surface Caps

    International Nuclear Information System (INIS)

    Piet, S. J.; Breckenridge, R. P.; Burns, D. E.

    2003-01-01

    Society has and will continue to generate hazardous wastes whose risks must be managed. For exceptionally toxic, long-lived, and feared waste, the solution is deep burial, e.g., deep geological disposal at Yucca Mtn. For some waste, recycle or destruction/treatment is possible. The alternative for other wastes is storage at or near the ground level (in someone's back yard); most of these storage sites include a surface barrier (cap) to prevent downward water migration. Some of the hazards will persist indefinitely. As society and regulators have demanded additional proof that caps are robust against more threats and for longer time periods, the caps have become increasingly complex and expensive. As in other industries, increased complexity will eventually increase the difficulty in estimating performance, in monitoring system/component performance, and in repairing or upgrading barriers as risks are managed. An approach leading to simpler, less expensive, longer-lived, more manageable caps is needed. Our project, which started in April 2002, aims to catalyze a Barrier Improvement Cycle (iterative learning and application) and thus enable Remediation System Performance Management (doing the right maintenance neither too early nor too late). The knowledge gained and the capabilities built will help verify the adequacy of past remedial decisions, improve barrier management, and enable improved solutions for future decisions. We believe it will be possible to develop simpler, longer-lived, less expensive caps that are easier to monitor, manage, and repair. The project is planned to: (a) improve the knowledge of degradation mechanisms in times shorter than service life; (b) improve modeling of barrier degradation dynamics; (c) develop sensor systems to identify early degradation; and (d) provide a better basis for developing and testing of new barrier systems. This project combines selected exploratory studies (benchtop and field scale), coupled effects accelerated

  15. Nuclear war survival skills

    International Nuclear Information System (INIS)

    Kearney, C.H.

    1979-09-01

    This book includes chapters on psychological preparations, warning and communications, and evacuation. It describes the building of expedient shelters, their ventilation and cooling, the purification and storage of adequate water, the processing and cooking of whole grains and legumes, fallout meters, protection against fires and carbon monoxide, and expedient furnishings for shelters. Other chapters cover sanitation and preventive medicine, medical advice for nuclear survivors lacking the help of doctors, improvised footwear and clothing, and advice on minimum preparations that can be made at low cost and should be made before a crisis arises. One appendix of the handbook gives detailed, field-tested instructions for building six types of earth-covered expedient fallout shelters, with criteria to guide the choice of which shelter to build. Others contain instructions for making an efficient shelter-ventilating pump and a homemade fallout meter that is accurate and dependable with inexpensive materials found in most households. This report is primarily a compilation and summary of civil defense measures and inventions developed at ORNL over the past 14 years and field-tested in six states, from Florida to Utah. It is the first comprehensive handbook of survival information for use by untrained citizens who want to improve their chances of surviving a possible nuclear attack. Sections may be easily excerpted and reproduced for mass distribution through news media

  16. 18F-Fluoroacetate - A longer lived acetate analogue for oncology studies with PET

    International Nuclear Information System (INIS)

    Khezami, Arbia; Ulrich, Eva; Matthies, Alexander; Ezziddin, Samer; Bender, Hans; Biersack, Hans-Juergen; Guhlke, Stefan

    2004-01-01

    Full text: Aim: 18 F-Fluoroacetate ( 18 Fac) can be considered as a fluoro analogue of 11C-acetate. Thus it may also be useful for oncologic PET studies. Like acetate, fluoroacetate is a substrate of the citric acid cycle, however in contrast to acetate it is an inhibitor of the enzyme Aconitase and thus no further metabolization of fluoroacetate occurs. The aim of this study was the in-vivo evaluation of this tracer with respect to tumor uptake in prostate carcinoma bearing nude mice as well as biodistribution and kinetics. Methods: The synthesis of 18 F-fluoroacetate was performed by using benzyl bromoacetate as precursor. The fluorinated ester was separated by HPLC, followed by basic hydrolysis and purification by use of anion exchange SEP-Pak chromatography. The formulation was performed by rinsing with water and subsequent elution of 18 Fac with sterile PBS-buffer and final sterile filtration. For the biodistribution studies, 3 groups of nude mice were inoculated with the prostate carcinoma cell lines PC3, DU-145 and LnCAP. After tumor growth, the animals were injected with 37-370 KBq of 18 Fac and bio-distributions performed at different times post injection. Results: The rcy of the substitution step was usually > 90%. The HPLC separation of the fluorinated ester and the precursor was performed on a C-18 column. The high UV-absorbance of the benzyl ester allows the determination of the specific activity of the tracer which was always lower than detection limits. Further, the injected animals did not show any signs of intoxication. The biodistribution studies revealed a primary biliary excretion. Regardless which cell line was used, accumulation of 18 Fac in tumor sites was well visible by PET-CT. Tumor to blood ratios increased with time. Conclusion: The synthesis of 18 Fac is straight forward and high radiochemical yields are typically obtained. The high specific activity of 18 F-fluoride allows injections of 18 Fac far below toxic concentrations. In nude

  17. Surviving starvation: essential role of the ghrelin-growth hormone axis.

    Science.gov (United States)

    Goldstein, J L; Zhao, T-j; Li, R L; Sherbet, D P; Liang, G; Brown, M S

    2011-01-01

    After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Mice were fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23 h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60 mg/dL. In Goat(-/-) mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20 mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

  18. Influence of diet quantity on learning and memory ability and immunological function in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    evaluate learning ability and the memory ability was retested at 24 hours later.Times of autonomic activity within 5 minutes were used to evaluate ability of autonomic activity.In addition,blood was collected from eyeball to measure plasma immune globulin and complement by using immunoturbidimetry.MAIN OUTCOME MEASURES:① Effect of different diet quantity on learning and memory ability;②effect of different diet quantity on times of autonomic activity and survival time under hypoxia and normal pressure;③ effect of different diet quantity on content of immune globulin and complement.RESULTS:All 80 mice were involved in the final analysis.① Effect of different diet quantity on learning and memory ability:There was no significant difference in learning ability during step down test (P>0.05).While,memory ability in the over-diet group and the quantitative-diet group was better than that in the over-limit diet group (t=2.235 - 2.423,P<0.05).During shuttle box test,learning and memory ability in the over-diet group was superior to that in the over-limit diet group (t =2.237 - 2.431,P<0.05).While,memory ability in the quantitative-diet group and quantitative-limit diet group was superior to that in the over-limit group (t =2.704 - 2.813,P<0.05).② Effect of different diet quantity on times of autonomic activity and survival time under hypoxia and normal pressure:There were significant differences in the times of autonomic activity among quantitative-diet group,quantitative-limit diet group and over-limit diet group (t=2.725 - 2.98,P<0.05).Survival time in the quantitative-diet group and the quantitative-limit diet group was longer than that in the over-diet group (7=2.365,2.719,P<0.05),but shorter than that in the over-limit diet group (t =2.427,2.538,P<0.05).While,survival time in the over-limit diet group was longer than that in the over-diet group (t =2.765,P<0.01).③Effect of different diet quantity on content of immune globulin and complement

  19. Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase.

    Science.gov (United States)

    Shiraishi, A; Sakumi, K; Sekiguchi, M

    2000-10-01

    O(6)-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the MGMT: gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. MGMT(-/-) mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD(50) values of MGMT(-/-) and MGMT(+/+) mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of MGMT(-/-) mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosou rea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of MGMT(+/+) and MGMT(-/-) mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ACNU produce O(6)-alkylguanine as a major toxic lesion, while cyclophosphamide yields other types of modifications in DNA which are not subjected to the action of the methyltransferase. MGMT(-/-) mice seem to be less refractory to the tumor-inducing effect of dacarbazine than are MGMT(+/+) mice. Thus, the level of O(6)-methylguanine-DNA methyltransferase activity is an important factor when determining susceptibility to drugs with the potential for alkylation.

  20. Strain-specific patterns of autonomic nervous system activity and heart failure susceptibility in mice.

    Science.gov (United States)

    Shusterman, Vladimir; Usiene, Irmute; Harrigal, Chivonne; Lee, Joon Sup; Kubota, Toru; Feldman, Arthur M; London, Barry

    2002-06-01

    Transgenic mice are widely used to study cardiac function, but strain-dependent differences in autonomic nervous system activity (ANSA) have not been explored. We compared 1) short-term pharmacological responses of cardiac rhythm in FVB vs. C57Black6/SV129 wild-type mice and 2) long-term physiological dynamics of cardiac rhythm and survival in tumor necrosis factor (TNF)-alpha transgenic mice with heart failure (TNF-alpha mice) on defined backgrounds. Ambulatory telemetry electrocardiographic recordings and response to saline, adrenergic, and cholinergic agents were examined in FVB and C57Black6/SV129 mice. In FVB mice, baseline heart rate (HR) was higher and did not change after injection of isoproterenol or atropine but decreased with propranolol. In C57Black6/SV129 mice, HR did not change with propranolol but increased with isoproterenol or atropine. Mean HR, but not indexes of HR variability, was an excellent predictor of response to autonomic agents. The proportion of surviving animals was higher in TNF-alpha mice on an FVB background than on a mixed FVB/C57Black6 background. The homeostatic states of ANSA are strain specific, which can explain the interstrain differences in mean HR, pharmacological responses, and survival of animals with congestive heart failure. Strain-specific differences should be considered in selecting the strains of mice used for transgenic and gene targeting experiments.

  1. Cheaters Are Looked at Longer and Remembered Better than Cooperators in Social Exchange Situations

    Directory of Open Access Journals (Sweden)

    Dan Chiappe

    2004-01-01

    Full Text Available What information is most salient during social exchange? Our studies assess the relative importance of cheaters and cooperators and whether their importance is affected by amount of resources involved in the exchange. In Experiment 1, participants categorized individuals as cheaters, cooperators, or neither, and rated how important they are to remember using a 7-point scale. In Experiment 2, participants categorized individuals, and then looked at their photos. This was followed by tests of face recognition, and memory for social contract status. Experiment 1 found cheaters were rated more important to remember than cooperators and more so when a greater amount of resources was involved. Experiment 2 found cheaters were looked at longer and people had better memory for their faces and were more likely to remember their social contract status. This suggests the mind evolved to remember information most pertinent in social contract situations.

  2. On the Nonsymmetric Longer Queue Model: Joint Distribution, Asymptotic Properties, and Heavy Traffic Limits

    Directory of Open Access Journals (Sweden)

    Charles Knessl

    2013-01-01

    Full Text Available We consider two parallel queues, each with independent Poisson arrival rates, that are tended by a single server. The exponential server devotes all of its capacity to the longer of the queues. If both queues are of equal length, the server devotes ν of its capacity to the first queue and the remaining 1−ν to the second. We obtain exact integral representations for the joint probability distribution of the number of customers in this two-node network. Then we evaluate this distribution in various asymptotic limits, such as large numbers of customers in either/both of the queues, light traffic where arrivals are infrequent, and heavy traffic where the system is nearly unstable.

  3. Targeted treatment trials for tuberous sclerosis and autism: no longer a dream.

    Science.gov (United States)

    Sahin, Mustafa

    2012-10-01

    Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual disability. Cell culture and mouse model experiments have identified the mTOR pathway as a therapeutic target in this disease. This review summarizes the advantages of using TSC as model of ASD and the recent advances in the translational and clinical treatment trials in TSC. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Inpatient cognitive behaviour therapy for adolescents with anorexia nervosa: immediate and longer-term effects

    Directory of Open Access Journals (Sweden)

    Riccardo eDalle Grave

    2014-02-01

    Full Text Available Introduction: Inpatient treatment for anorexia nervosa is often successful in restoring body weight, but a high percentage of patients relapse following discharge. The aim of the present study was to establish the immediate and longer-term effects of a novel inpatient program for adolescents that was designed to produce enduring change. Method: Twenty-seven consecutive patients with severe anorexia nervosa were admitted to a 20-week inpatient treatment program based upon enhanced cognitive behaviour therapy (CBT-E. The patients were assessed before and after hospitalization, and six and 12 months later. Results: Twenty-six patients (96% completed the program. In these patients there was a substantial improvement in weight, eating disorder features and general psychopathology that was well maintained at 12-month follow-up. Conclusions: These findings suggest that inpatient CBT-E is a promising approach to the treatment of adolescents with severe anorexia nervosa.

  5. Poststroke Trajectories: The Process of Recovery Over the Longer Term Following Stroke.

    Science.gov (United States)

    Hawkins, Rebecca J; Jowett, Adam; Godfrey, Mary; Mellish, Kirste; Young, John; Farrin, Amanda; Holloway, Ivana; Hewison, Jenny; Forster, Anne

    2017-01-01

    We adopted a grounded theory approach to explore the process of recovery experienced by stroke survivors over the longer term who were living in the community in the United Kingdom, and the interacting factors that are understood to have shaped their recovery trajectories. We used a combination of qualitative methods. From the accounts of 22 purposively sampled stroke survivors, four different recovery trajectories were evident: (a) meaningful recovery, (b) cycles of recovery and decline, (c) ongoing disruption, (d) gradual, ongoing decline. Building on the concept of the illness trajectory, our findings demonstrate how multiple, interacting factors shape the process and meaning of recovery over time. Such factors included conception of recovery and meanings given to the changing self, the meanings and consequences of health and illness experiences across the life course, loss, sense of agency, and enacting relationships. Awareness of the process of recovery will help professionals better support stroke survivors.

  6. Studies on irradiated BNFL culture medium for decontamination and longer storage

    International Nuclear Information System (INIS)

    Singh, Antaryami; Malodia, P.; Jain, S.K.; Ram Gopal

    2001-01-01

    The feasibility of gamma radiation for microbial decontamination and shelf-life extension of culture medium was studied. Changes in total viable count, coliform count and fungal count on exposure to 5, 10, 15, 20 and 25 kGy of gamma radiation were examined. The total viable counts were reduced on irradiation. Complete destruction of bacterial and fungal contamination was observed at 20 kGy. Studies were conducted to examine the changes in microbial contamination of the medium during storage. There was no post irradiation proliferation of microorganisms. Also, no significant change in the efficiency of the irradiated culture medium was observed. Thus, irradiation is extremely useful for longer storage and quality-assurance. (author)

  7. Changing Zaire to Congo: the fate of no-longer relevant mnemonic information.

    Science.gov (United States)

    Eriksson, Johan; Stiernstedt, Mikael; Öhlund, Maria; Nyberg, Lars

    2014-11-01

    In an ever-changing world there is constant pressure on revising long-term memory, such when people or countries change name. What happens to the old, pre-existing information? One possibility is that old associations gradually are weakened and eventually lost. Alternatively, old and no longer relevant information may still be an integral part of memory traces. To test the hypothesis that old mnemonic information still becomes activated when people correctly retrieve new, currently relevant information, brain activity was measured with fMRI while participants performed a cued-retrieval task. Paired associates (symbol-sound and symbol-face pairs) were first learned during two days. Half of the associations were then updated during the next two days, followed by fMRI scanning on day 5 and also 18 months later. As expected, retrieval reactivated sensory cortex related to the most recently learned association (visual cortex for symbol-face pairs, auditory cortex for symbol-sound pairs). Critically, retrieval also reactivated sensory cortex related to the no-longer relevant associate. Eighteen months later, only non-updated symbol-face associations were intact. Intriguingly, a subset of the updated associations was now treated as though the original association had taken over, in that memory performance was significantly worse than chance and that activity in sensory cortex for the original but not the updated associate correlated (negatively) with performance. Moreover, the degree of "residual" reactivation during day 5 inversely predicted memory performance 18 months later. Thus, updating of long-term memory involves adding new information to already existing networks, in which old information can stay resilient for a long time. Copyright © 2014. Published by Elsevier Inc.

  8. Using quality scores and longer reads improves accuracy of Solexa read mapping

    Directory of Open Access Journals (Sweden)

    Xuan Zhenyu

    2008-02-01

    Full Text Available Abstract Background Second-generation sequencing has the potential to revolutionize genomics and impact all areas of biomedical science. New technologies will make re-sequencing widely available for such applications as identifying genome variations or interrogating the oligonucleotide content of a large sample (e.g. ChIP-sequencing. The increase in speed, sensitivity and availability of sequencing technology brings demand for advances in computational technology to perform associated analysis tasks. The Solexa/Illumina 1G sequencer can produce tens of millions of reads, ranging in length from ~25–50 nt, in a single experiment. Accurately mapping the reads back to a reference genome is a critical task in almost all applications. Two sources of information that are often ignored when mapping reads from the Solexa technology are the 3' ends of longer reads, which contain a much higher frequency of sequencing errors, and the base-call quality scores. Results To investigate whether these sources of information can be used to improve accuracy when mapping reads, we developed the RMAP tool, which can map reads having a wide range of lengths and allows base-call quality scores to determine which positions in each read are more important when mapping. We applied RMAP to analyze data re-sequenced from two human BAC regions for varying read lengths, and varying criteria for use of quality scores. RMAP is freely available for downloading at http://rulai.cshl.edu/rmap/. Conclusion Our results indicate that significant gains in Solexa read mapping performance can be achieved by considering the information in 3' ends of longer reads, and appropriately using the base-call quality scores. The RMAP tool we have developed will enable researchers to effectively exploit this information in targeted re-sequencing projects.

  9. Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

    Science.gov (United States)

    Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi

    2017-10-01

    The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Slower Perception Followed by Faster Lexical Decision in Longer Words: A Diffusion Model Analysis.

    Science.gov (United States)

    Oganian, Yulia; Froehlich, Eva; Schlickeiser, Ulrike; Hofmann, Markus J; Heekeren, Hauke R; Jacobs, Arthur M

    2015-01-01

    Effects of stimulus length on reaction times (RTs) in the lexical decision task are the topic of extensive research. While slower RTs are consistently found for longer pseudo-words, a finding coined the word length effect (WLE), some studies found no effects for words, and yet others reported faster RTs for longer words. Moreover, the WLE depends on the orthographic transparency of a language, with larger effects in more transparent orthographies. Here we investigate processes underlying the WLE in lexical decision in German-English bilinguals using a diffusion model (DM) analysis, which we compared to a linear regression approach. In the DM analysis, RT-accuracy distributions are characterized using parameters that reflect latent sub-processes, in particular evidence accumulation and decision-independent perceptual encoding, instead of typical parameters such as mean RT and accuracy. The regression approach showed a decrease in RTs with length for pseudo-words, but no length effect for words. However, DM analysis revealed that the null effect for words resulted from opposing effects of length on perceptual encoding and rate of evidence accumulation. Perceptual encoding times increased with length for words and pseudo-words, whereas the rate of evidence accumulation increased with length for real words but decreased for pseudo-words. A comparison between DM parameters in German and English suggested that orthographic transparency affects perceptual encoding, whereas effects of length on evidence accumulation are likely to reflect contextual information and the increase in available perceptual evidence with length. These opposing effects may account for the inconsistent findings on WLEs.

  11. Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

    International Nuclear Information System (INIS)

    O'Higgins, N.; Brady, H.R.; Clark, C.G.

    1984-01-01

    A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

  12. Embryotoxicity of arsenite and arsenate. Distribution in pregnant mice and monkeys and effects on embryonic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lindgren, A; Danielsson, R G; Dencker, L [Department of Toxicology, Biomedical Center, Uppsala University, Sweden; Vahter, M [National Institute of Environmental Medicine, Stockholm, Sweden

    1984-01-01

    The distribution of /sup 74/As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the /sup 74/As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution pucture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10..mu..M) while arsenate seemed to be without effect at concentrations up to 200 ..mu..M (highest tested). Arsenate, however, showed a potential of the arsenite toxicity.

  13. Embryotoxicity of arsenite and arsenate. Distribution in pregnant mice and monkeys and effects on embryonic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lindgren, A; Danielsson, R G; Dencker, L [Department of Toxicology, Biomedical Center, Uppsala University, Sweden; Vahter, M [National Institute of Environmental Medicine, Stockholm, Sweden

    1984-01-01

    The distribution of /sup 74/As-labelled and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the /sup 74/As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10..mu..M) while arsenate seemed to be without effect at concentrations up to 200 ..mu..M (highest tested). Arsenate, however, showed a potential of the arsenite toxicity.

  14. Disparities in cervical cancer survival among Asian-American women.

    Science.gov (United States)

    Nghiem, Van T; Davies, Kalatu R; Chan, Wenyaw; Mulla, Zuber D; Cantor, Scott B

    2016-01-01

    We compared overall survival and influencing factors between Asian-American women as a whole and by subgroup with white women with cervical cancer. Cervical cancer data were from the Surveillance, Epidemiology, and End Results registry; socioeconomic information was from the Area Health Resource File. We used standard tests to compare characteristics between groups; the Kaplan-Meier method with log-rank test to assess overall survival and compare it between groups; and Cox proportional hazards models to determine the effect of race and other covariates on overall survival (with and/or without age stratification). Being 3.3 years older than white women at diagnosis (P Asian-American women were more likely to be in a spousal relationship, had more progressive disease, and were better off socioeconomically. Women of Filipino, Japanese, and Korean origin had similar clinical characteristics compared to white women. Asian-American women had higher 36- and 60-month survival rates (P = .004 and P = .013, respectively), higher overall survival rates (P = .049), and longer overall survival durations after adjusting for age and other covariates (hazard ratio = 0.77, 95% confidence interval: 0.68-0.86). Overall survival differed across age strata between the two racial groups. With the exception of women of Japanese or Korean origin, Asian-American women grouped by geographic origin had better overall survival than white women. Although Asian-American women, except those of Japanese or Korean origin, had better overall survival than white women, their older age at cervical cancer diagnosis suggests that they have less access to screening programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Disparities in cervical cancer survival among Asian American women

    Science.gov (United States)

    Nghiem, Van T.; Davies, Kalatu R.; Chan, Wenyaw; Mulla, Zuber D.; Cantor, Scott B.

    2015-01-01

    Purpose We compared overall survival and influencing factors between Asian American women as a whole and by subgroup with white women with cervical cancer. Methods Cervical cancer data were from the Surveillance, Epidemiology, and End Results registry; socioeconomic information was from the Area Health Resource File. We used standard tests to compare characteristics between groups; the Kaplan-Meier method with log-rank test to assess overall survival and compare it between groups; and Cox proportional hazards models to determine the effect of race and other covariates on overall survival (with/without age-stratification). Results Being 3.3 years older than white women at diagnosis (pAsian American women were more likely to be in a spousal relationship, had more progressive disease, and were better off socioeconomically. Women of Filipino, Japanese, and Korean origin had similar clinical characteristics compared with white women. Asian American women had higher 36- and 60-month survival rates (p=0.004 and p=0.013, respectively), higher overall survival rates (p=0.049), and longer overall survival durations after adjusting for age and other covariates (hazard ratio=0.77, 95% confidence interval: 0.68–0.86). Overall survival differed across age strata between the two racial groups. With the exception of women of Japanese or Korean origin, Asian American women grouped by geographic origin had better overall survival than white women. Conclusions Although Asian American women, except those of Japanese or Korean origin, had better overall survival than white women, their older age at cervical cancer diagnosis suggests that they have less access to screening programs. PMID:26552330

  16. Induction of protective immunity against toxoplasmosis in mice by ...

    African Journals Online (AJOL)

    The results showed that mice immunized by pcROP1 with or without alum produced high Th1 immune response compared with control groups. This type of DNA vaccine prolonged slightly the survival time. The current study showed that ROP1 DNA vaccine can induced partial protective response against toxoplasmosis.

  17. High death rate in mice treated topically with diclofenac

    DEFF Research Database (Denmark)

    Lerche, Catharina M; Philipsen, Peter A; Poulsen, Thomas

    2011-01-01

    ). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac-treated groups and control groups (P...

  18. Expression of oxidative phosphorylation components in mitochondria of long-living Ames dwarf mice.

    Science.gov (United States)

    Brown-Borg, Holly M; Johnson, W Thomas; Rakoczy, Sharlene G

    2012-02-01

    Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is associated with extended life span in several species. Ames dwarf mice are GH-deficient and live >50% longer than wild-type littermates. Previously, we have shown that tissues from Ames mice exhibit elevated levels of antioxidative enzymes, less H(2)O(2) production, and lower oxidative damage suggesting that mitochondrial function may differ between genotypes. To explore the relationship between hormone deficiency and mitochondria in mice with extended longevity, we evaluated activity, protein, and gene expression of oxidative phosphorylation components in dwarf and wild-type mice at varying ages. Liver complex I + III activity was higher in dwarf mice compared to wild-type mice. The activity of I + III decreased between 3 and 20 months of age in both genotypes with greater declines in wild-type mice in liver and skeletal muscle. Complex IV activities in the kidney were elevated in 3- and 20-month-old dwarf mice relative to wild-type mice. In Ames mice, protein levels of the 39 kDa complex I subunit were elevated at 20 months of age when compared to wild-type mouse mitochondria for every tissue examined. Kidney and liver mitochondria from 20-month-old dwarf mice had elevated levels of both mitochondrially-encoded and nuclear-encoded complex IV proteins compared to wild-type mice (p dwarf mice. Overall, we found that several components of the oxidative phosphorylation (OXPHOS) system were elevated in Ames mice. Mitochondrial to nuclear DNA ratios were not different between genotypes despite the marked increase in PGC-1α levels in dwarf mice. The increased OXPHOS activities, along with lower ROS production in dwarf mice, predict enhanced mitochondrial function and efficiency, two factors likely contributing to long-life in Ames mice.

  19. Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

    International Nuclear Information System (INIS)

    Sanchez, A.; Lundgren, D.L.; McClellan, R.O.

    1976-01-01

    The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90 Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD 50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90 Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

  20. EFFECT OF BACILLUS OF CALMETTE-GUÉRIN, AVRIDINE AND Propionibacterium acnes AS IMMUNOMODULATORS ON RABIES IN MICE

    Directory of Open Access Journals (Sweden)

    MEGID J.

    1999-01-01

    Full Text Available The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-g (IFN-g were found in infected mice. The intra-pad inoculation test (IPI was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN antibodies titers, IFN-g concentration and MIF response.

  1. Survival benefits of remote ischemic conditioning in sepsis.

    Science.gov (United States)

    Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2017-06-01

    Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an

  2. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Science.gov (United States)

    Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

    2014-01-01

    Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  3. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Directory of Open Access Journals (Sweden)

    Zhe Liang

    Full Text Available Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis.Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival.In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice.Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  4. [Intensive care medicine-survival and prospect of life].

    Science.gov (United States)

    Valentin, A

    2017-10-01

    Intensive care medicine has achieved a significant increase in survival rates from critical illness. In addition to short-term outcomes like intensive care unit or hospital mortality, long-term prognosis and prospect of life of intensive care patients have recently become increasingly important. Pure survival is no longer a sole goal of intensive care medicine. The prediction of an intensive care patient's individual course should include the period after intensive care. A relevant proportion of all intensive care patients is affected by physical, psychological, cognitive, and social limitations after discharge from the intensive care unit. The prognosis of the status of the patient after discharge from the intensive care unit is an important part of the decision-making process with respect to the implementation or discontinuation of intensive care measures. The heavy burden of intensive care treatment should not solely be argued by pure survival but an anticipated sound prospect of life.

  5. Association of collagen architecture with glioblastoma patient survival.

    Science.gov (United States)

    Pointer, Kelli B; Clark, Paul A; Schroeder, Alexandra B; Salamat, M Shahriar; Eliceiri, Kevin W; Kuo, John S

    2017-06-01

    OBJECTIVE Glioblastoma (GBM) is the most malignant primary brain tumor. Collagen is present in low amounts in normal brain, but in GBMs, collagen gene expression is reportedly upregulated. However, to the authors' knowledge, direct visualization of collagen architecture has not been reported. The authors sought to perform the first direct visualization of GBM collagen architecture, identify clinically relevant collagen signatures, and link them to differential patient survival. METHODS Second-harmonic generation microscopy was used to detect collagen in a GBM patient tissue microarray. Focal and invasive GBM mouse xenografts were stained with Picrosirius red. Quantitation of collagen fibers was performed using custom software. Multivariate survival analysis was done to determine if collagen is a survival marker for patients. RESULTS In focal xenografts, collagen was observed at tumor brain boundaries. For invasive xenografts, collagen was intercalated with tumor cells. Quantitative analysis showed significant differences in collagen fibers for focal and invasive xenografts. The authors also found that GBM patients with more organized collagen had a longer median survival than those with less organized collagen. CONCLUSIONS Collagen architecture can be directly visualized and is different in focal versus invasive GBMs. The authors also demonstrate that collagen signature is associated with patient survival. These findings suggest that there are collagen differences in focal versus invasive GBMs and that collagen is a survival marker for GBM.

  6. Biofilm formation enhances Helicobacter pylori survivability in vegetables.

    Science.gov (United States)

    Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

    2017-04-01

    To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Zoopharmacognosy in diseased laboratory mice: conflicting evidence.

    Directory of Open Access Journals (Sweden)

    Minesh Kapadia

    Full Text Available Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY, an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

  8. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  9. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  10. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    and that suicide has become a subject of research, prevention and treatment. Auxiliary Strategies In the 1990s there have been established the Centre for Suicide Research and the Centre for Prevention of Suicide in Denmark and there has been drafted a national policy document which focuses on the need......We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...

  11. 16,16-dimethyl prostaglandin E/sub 2/ increases survival of murine intestinal stem cells when given before photon radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.R.; Thomas, C.

    1983-11-01

    A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE/sub 2/, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after /sup 137/Cs gamma(..gamma..) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE/sub 2/ was given before but not after /sup 137/Cs ..gamma.. irradiation. The maximum degree of 16,16-dimethyl PGE/sub 2/-induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE/sub 2/ and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE/sub 2/ may in part be protected from the lethal effects of ionizing photon radiation.

  12. Short-term fasting protects mice against γ ray radiation

    International Nuclear Information System (INIS)

    Zhu Shengnan; Gu Xiuling; Song Lian; Tong Jian; Li Jianxiang

    2012-01-01

    Objective: To investigate the antagonistic effects of short-term fasting against 60 Co γ ray radiation. Methods: After fasting ICR mice were irradiated for 3 min at a dose rate of 2.5 Gy/min and then returned to normal diet. General situation, body weight changes, food consumption and toxic status were observed. WBC, organ index and anti-oxidative ability (ROS, SOD, MDA, T-AOC) were analyzed. Results: After 60 Co γ ray radiation, the mice exhibited severe toxic symptoms before death. The survival rates were 0 for control and 12 h group, 12.5% for 48 h group and 50% for 72 h group respectively. ROS production of 72 h group was reduced compared with 0 h group (P<0.05). Conclusion: Short-term fasting may attenuate radiation induced injuries, evidenced by a significant increase in mice survival rate. (authors)

  13. 44 CFR 65.14 - Remapping of areas for which local flood protection systems no longer provide base flood protection.

    Science.gov (United States)

    2010-10-01

    ... local flood protection systems no longer provide base flood protection. 65.14 Section 65.14 Emergency... § 65.14 Remapping of areas for which local flood protection systems no longer provide base flood... process of restoring a flood protection system that was: (i) Constructed using Federal funds; (ii...

  14. Allopurinol, indomethacin and riboflavin enhance radiation lethality in mice

    International Nuclear Information System (INIS)

    Floersheim, G.L.

    1994-01-01

    Two widely used drugs, allopurinol and indomethacin, and the vitamin riboflavin increased the response of mice to ionizing radiation. In mice a dose of 10.5 Gy of γ rays from a 60 Co source resulted in a dose-dependent shortening of survival times after pretreatment with the three agents, applied at doses which were well tolerated alone. When the dose dependency of these drugs on the influence on survival was tested, two response patterns emerged. Indomethacin (25 mg/kg) shifted the survival curve to the left and reduced the LD 50 from ∼6.5 Gy to ∼4.5 Gy. Allopurinol (100 mg/kg) diminished the survival rate to approximately 50% irrespective of the radiation dose (ranging from 0.75 to 6.0 Gy). A similar though less striking trend was seen with riboflavin (120 mg/kg), which reduced the survival rate to approximately 65% in the dose range from 3 to 6 Gy. Mortality in mice treated with allopurinol or riboflavin and irradiated with nonlethal exposures (from radiation alone) occurred within the first few days after irradiation, suggesting a different type of injury than is usually associated with radiation death. Although doses of the three drugs used clinically are clearly lower than those providing enhanced radioresponse in our experiments, subtle and nonovert injury caused by combined exposure to the drugs and radiation cannot be completely excluded. 31 refs., 4 figs., 5 tabs

  15. Exploring the 'permanent forest' paradigm: might renewable commercial forest estates lead to greater net greenhouse abatement over the longer term?

    International Nuclear Information System (INIS)

    Anderson, Graeme

    2007-01-01

    Full text: Understanding permanence: A common perception exists which suggests that long term or 'permanent' tree plantings are considered a superior form of (post 1990) carbon sink, and commercial plantations (which allow for harvesting and replanting) are less useful for abatement. However, common to all forms of forest carbon sink is the issue of permanence. None of these are truly permanent stores of carbon because at any point either a fire, disease, harvest or major event can mean part of the carbon store is released. Why then the perceived bias against sink projects which allow for commercial harvesting and replanting? Let's not forget - things are getting hotter: Australian projections for climate change provide plenty of challenges for current and future forest managers. Over the next century many key forest species may have to endure conditions outside their'current growing range. This poses risks for the emergent offsets industry which needs to be actively managed. Simply planting local indigenous species alone may no longer be the only best practice. Think 'true fate of carbon': It is important that our thinking is not constrained by current rules, as these will continually be refined as our knowledge about carbon systems improves over the next century (between now and 2100 there will be 22 post-Kyoto negotiation periods). Our key focus should be in considering the 'true fate' of carbon, and the real contribution to greenhouse abatement. Policy makers need to keep this in mind, and ensure that the entire carbon life cycle is considered in their decision making. 'Standing forest' versus 'Net abatement effect': There are two effective means for forests to achieve genuine greenhouse abatement. One is the carbon sequestered and stored in the 'standing forest', the other is the greenhouse benefit (carbon flow or net abatement effect) of an ongoing and renewable supply of tree based products from the site (wood, fibre, biomass, biofuel), which replace

  16. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

    Science.gov (United States)

    Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2009-06-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.

  17. Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night

    Directory of Open Access Journals (Sweden)

    Sophia Schiza

    2015-06-01

    Full Text Available The prevalence of obstructive sleep apnoea (OSA is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF.

  18. Relation between delay and survival in 596 patients with breast cancer.

    Science.gov (United States)

    Machiavelli, M; Leone, B; Romero, A; Perez, J; Vallejo, C; Bianco, A; Rodriguez, R; Estevez, R; Chacon, R; Dansky, C

    1989-01-01

    To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

  19. Object Categorization in Finer Levels Relies More on Higher Spatial Frequencies and Takes Longer.

    Science.gov (United States)

    Ashtiani, Matin N; Kheradpisheh, Saeed R; Masquelier, Timothée; Ganjtabesh, Mohammad

    2017-01-01

    The human visual system contains a hierarchical sequence of modules that take part in visual perception at different levels of abstraction, i.e., superordinate, basic, and subordinate levels. One important question is to identify the "entry" level at which the visual representation is commenced in the process of object recognition. For a long time, it was believed that the basic level had a temporal advantage over two others. This claim has been challenged recently. Here we used a series of psychophysics experiments, based on a rapid presentation paradigm, as well as two computational models, with bandpass filtered images of five object classes to study the processing order of the categorization levels. In these experiments, we investigated the type of visual information required for categorizing objects in each level by varying the spatial frequency bands of the input image. The results of our psychophysics experiments and computational models are consistent. They indicate that the different spatial frequency information had different effects on object categorization in each level. In the absence of high frequency information, subordinate and basic level categorization are performed less accurately, while the superordinate level is performed well. This means that low frequency information is sufficient for superordinate level, but not for the basic and subordinate levels. These finer levels rely more on high frequency information, which appears to take longer to be processed, leading to longer reaction times. Finally, to avoid the ceiling effect, we evaluated the robustness of the results by adding different amounts of noise to the input images and repeating the experiments. As expected, the categorization accuracy decreased and the reaction time increased significantly, but the trends were the same. This shows that our results are not due to a ceiling effect. The compatibility between our psychophysical and computational results suggests that the temporal

  20. How diking affects the longer-term structure and evolution of divergent plate boundaries

    KAUST Repository

    Trippanera, Daniele

    2015-04-01

    Recurrent diking episodes along divergent plate boundaries, as at Dabbahu (2005, Afar) or at Bardarbunga (2014, Iceland) , highlight the possibility to have m-wide opening in a short time (days to weeks). This suggests a prominent role of magma enhancing transient plate separations. However, the role of diking on a longer term (> 102 years) and its influence on the structure and the evolution of a divergent plate boundary is still poorly investigated. Here we use field surveys along the oceanic Icelandic and continental Ethiopian plate boundaries, along five eruptive fissures and four rift segments. Field observations have also been integrated with analogue and numerical models of dike emplacement to better understand the effect of dike emplacement at depth and at the surface. Our results show that the dike-fed eruptive fissures are systematically associated with graben structures formed by inward dipping normal faults having throws up to 10 m and commonly propagating downward. Moreover, rift segments (i.e. mature rift zones), despite any asymmetry and repetition, are characterized by the same features as the eruptive fissures, the only difference lying in the larger size (higher fault throws, up to 40 m, and wider deformation zones). Analogue and numerical models of dike intrusion confirm that all the structural features observed along the rift segments may be dike-induced; these features include downward propagating normal faults bordering graben structures, contraction at the base of the hanging walls of the faults and upward propagating faults. Simple calculations based on the deeper structure of the eroded rift segments in eastern and western Iceland also suggest that all the fault slip in the active rift segments may result from diking. These results suggest that the overall deformation pattern of eruptive fissures and rift segments may be explained only by dike emplacement. In a magmatic rift, the regional tectonic stress may rarely be high enough to be

  1. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  2. The MICE Online Systems

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

  3. The Efficiency of Infants' Exploratory Play Is Related to Longer-Term Cognitive Development

    Science.gov (United States)

    Muentener, Paul; Herrig, Elise; Schulz, Laura

    2018-01-01

    In this longitudinal study we examined the stability of exploratory play in infancy and its relation to cognitive development in early childhood. We assessed infants' (N = 130, mean age at enrollment = 12.02 months, SD = 3.5 months; range: 5–19 months) exploratory play four times over 9 months. Exploratory play was indexed by infants' attention to novelty, inductive generalizations, efficiency of exploration, face preferences, and imitative learning. We assessed cognitive development at the fourth visit for the full sample, and again at age three for a subset of the sample (n = 38). The only measure that was stable over infancy was the efficiency of exploration. Additionally, infants' efficiency score predicted vocabulary size and distinguished at-risk infants recruited from early intervention sites from those not at risk. Follow-up analyses at age three provided additional evidence for the importance of the efficiency measure: more efficient exploration was correlated with higher IQ scores. These results suggest that the efficiency of infants' exploratory play can be informative about longer-term cognitive development. PMID:29904360

  4. Square Helmholtz coil with homogeneous field for magnetic measurement of longer HTS tapes

    Energy Technology Data Exchange (ETDEWEB)

    Alamgir, A.K.M. [Applied Superconductivity Research Center, Department of Physics, Building Li Zhai, Room 209, Tsinghua University, Beijing 100084 (China)]. E-mail: alam643@hotmail.com; Fang, J. [Applied Superconductivity Research Center, Department of Physics, Building Li Zhai, Room 209, Tsinghua University, Beijing 100084 (China); Gu, C. [Applied Superconductivity Research Center, Department of Physics, Building Li Zhai, Room 209, Tsinghua University, Beijing 100084 (China); Han, Z. [Applied Superconductivity Research Center, Department of Physics, Building Li Zhai, Room 209, Tsinghua University, Beijing 100084 (China)

    2005-08-01

    Magnetic ac loss measurement of HTS tapes and films at various magnetic field orientations becomes a crucial issue from the view point of measurement precision. In principle, due to tiny loss component and anisotropic properties, longer HTS sample subjected to very good homogeneous field could facilitate the accuracy of this kind of measurement. We investigated field profile of Helmholtz coils with square winding as a magnetizer for HTS tape and films. It is found that square winding exhibits better field-homogeneity than that of conventional circular winding with the similar coil dimensions for ideal condition. Being apart from ideal condition, we investigated field profile of square Helmholtz coil with various combinations of coil parameters and made a conclusion for the best combination based on the field homogeneity and field intensity. The design also provides noise reduction facilities by allowing compact and identical pick up-compensation coil arrangement. In addition, we optimized the final design of Helmholtz coil to compensate the influence of difficulties in square winding on the field distribution. Finally, as small as 0.5% field variation was estimated for 50 mm long sample to be magnetized under a proper combination of fabrication parameters. Investigation of field homogeneity, noise effect and a practical design of square Helmholtz coil as a pick-up coil based magnetizer will be reported.

  5. Development of longer Nd:LGGG crystal for high power laser application

    Science.gov (United States)

    Yin, Yanru; Tian, Hanlin; Zhang, Jian; Mu, Wenxiang; Zhang, Baitao; Jia, Zhitai; He, Jingliang; Tao, Xutang

    2017-11-01

    In order to further improve the Nd3+:(LuxGd1-x)3Ga5O12 (Nd:LGGG) crystal performance in high power laser field, a long Nd:LGGG crystal with dimensions of Φ 23 × 112 mm3 has been grown successfully by the Czochralski (Cz) method for laser rod fabrication. Compared with the normal size LGGG crystals (like 30-50 mm in length), we overcame several difficulties in the growth of longer ones, including crystal cracking by a large longitudinal temperature gradient, spiral growth by a small radial temperature gradient, and growth instability and even constitutional super cooling by Ga2O3 volatilizing continuously. The doping concentrations of Nd3+ and Lu3+ in the as-grown crystal and the crystal optical quality have been measured. The performance of diode-side-pumped Nd:LGGG rod laser has been preliminarily tested for the first time, simply by replacing the Nd:YAG crystal rod inside a commercial laser module. Under an incident pump power of 160 W, the maximum continuous wave output power of 38 W has been obtained, corresponding to an optical-optical conversion efficiency of 23.8% and a slope efficiency of 40.8%, respectively.

  6. Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children.

    Science.gov (United States)

    Morato, Manuela; Correia-Costa, Liane; Sousa, Teresa; Cosme, Dina; Schaefer, Franz; Areias, José Carlos; Guerra, António; Afonso, Alberto Caldas; Barros, Henrique; Azevedo, Ana; Albino-Teixeira, António

    2017-08-01

    We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H 2 O 2 ) play a role in the putative association. Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H 2 O 2 by a microplate fluorometric assay. U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H 2 O 2 decreased with P-AGT. A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H 2 O 2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.

  7. The bleeding time may be longer in children than in adults.

    Science.gov (United States)

    Sanders, J M; Holtkamp, C A; Buchanan, G R

    1990-01-01

    The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.

  8. 124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Giuseppe Lucio Cascini

    2014-01-01

    Full Text Available 124Iodine (124I with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

  9. Suppression of no-longer relevant information in Working Memory: An alpha-power related mechanism?

    Science.gov (United States)

    Poch, Claudia; Valdivia, María; Capilla, Almudena; Hinojosa, José Antonio; Campo, Pablo

    2018-03-27

    Selective attention can enhance Working Memory (WM) performance by selecting relevant information, while preventing distracting items from encoding or from further maintenance. Alpha oscillatory modulations are a correlate of visuospatial attention. Specifically, an enhancement of alpha power is observed in the ipsilateral posterior cortex to the locus of attention, along with a suppression in the contralateral hemisphere. An influential model proposes that the alpha enhancement is functionally related to the suppression of information. However, whether ipsilateral alpha power represents a mechanism through which no longer relevant WM representations are inhibited has yet not been explored. Here we examined whether the amount of distractors to be suppressed during WM maintenance is functionally related to alpha power lateralized activity. We measure EEG activity while participants (N = 36) performed a retro-cue task in which the WM load was varied across the relevant/irrelevant post-cue hemifield. We found that alpha activity was lateralized respect to the locus of attention, but did not track post-cue irrelevant load. Additionally, non-lateralized alpha activity increased with post-cue relevant load. We propose that alpha lateralization associated to retro-cuing might be related to a general orienting mechanism toward relevant representation. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Diminish electrostatic in piezoresponse force microscopy through longer or ultra-stiff tips

    Science.gov (United States)

    Gomez, A.; Puig, T.; Obradors, X.

    2018-05-01

    Piezoresponse Force Microscopy is a powerful but delicate nanoscale technique that measures the electromechanical response resulting from the application of a highly localized electric field. Though mechanical response is normally due to piezoelectricity, other physical phenomena, especially electrostatic interaction, can contribute to the signal read. We address this problematic through the use of longer ultra-stiff probes providing state of the art sensitivity, with the lowest electrostatic interaction and avoiding working in high frequency regime. In order to find this solution we develop a theoretical description addressing the effects of electrostatic contributions in the total cantilever vibration and its quantification for different setups. The theory is subsequently tested in a Periodically Poled Lithium Niobate (PPLN) crystal, a sample with well-defined 0° and 180° domains, using different commercial available conductive tips. We employ the theoretical description to compare the electrostatic contribution effects into the total phase recorded. Through experimental data our description is corroborated for each of the tested commercially available probes. We propose that a larger probe length can be a solution to avoid electrostatic forces, so the cantilever-sample electrostatic interaction is reduced. Our proposed solution has great implications into avoiding artifacts while studying soft biological samples, multiferroic oxides, and thin film ferroelectric materials.

  11. Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies.

    Science.gov (United States)

    Hafkamp, Maurits P J; Slaets, Joris P J; van Bodegom, David

    2017-05-30

    Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 ( p = 0.02) and 0.18 ( p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity.

  12. Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients

    DEFF Research Database (Denmark)

    Rygård, Sofie L; Jonsson, Andreas B; Madsen, Martin B

    2018-01-01

    on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients. METHODS: We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue...... blood. RESULTS: We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97-1.11; 7349 patients; TSA......-adjusted CI 0.93-1.15), adverse events (1.26, 0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required...

  13. Square Helmholtz coil with homogeneous field for magnetic measurement of longer HTS tapes

    International Nuclear Information System (INIS)

    Alamgir, A.K.M.; Fang, J.; Gu, C.; Han, Z.

    2005-01-01

    Magnetic ac loss measurement of HTS tapes and films at various magnetic field orientations becomes a crucial issue from the view point of measurement precision. In principle, due to tiny loss component and anisotropic properties, longer HTS sample subjected to very good homogeneous field could facilitate the accuracy of this kind of measurement. We investigated field profile of Helmholtz coils with square winding as a magnetizer for HTS tape and films. It is found that square winding exhibits better field-homogeneity than that of conventional circular winding with the similar coil dimensions for ideal condition. Being apart from ideal condition, we investigated field profile of square Helmholtz coil with various combinations of coil parameters and made a conclusion for the best combination based on the field homogeneity and field intensity. The design also provides noise reduction facilities by allowing compact and identical pick up-compensation coil arrangement. In addition, we optimized the final design of Helmholtz coil to compensate the influence of difficulties in square winding on the field distribution. Finally, as small as 0.5% field variation was estimated for 50 mm long sample to be magnetized under a proper combination of fabrication parameters. Investigation of field homogeneity, noise effect and a practical design of square Helmholtz coil as a pick-up coil based magnetizer will be reported

  14. No longer "if," but "when": the coming abbreviated approval pathway for follow-on biologics.

    Science.gov (United States)

    Kelly, Jeremiah J; David, Michael

    2009-01-01

    Abbreviated approval of follow-on biologics involves answering complex scientific, legal, and policy questions. The Food and Drug Administration (FDA or the Agency) asserts that it lacks the statutory authority to approve follow-on versions of biologics licensed under Section 351 of the Public Health Service Act (PHSA). Despite persuasive arguments to the contrary the one hundred and tenth Congress entertained four legislative proposals to give FDA this authority, each markedly different. It is no longer a question of "if," but "when" FDA will receive authority to review and license abbreviated applications for follow-on biologics. Any legislation in the one hundred and eleventh Congress must determine: (1) if FDA should be granted authority to develop an abbreviated pathway through rulemaking or guidance; (2) if human clinical trials should be mandatory or discretionary; (3) the feasibility of interchangeability determinations in light of patient safety concerns; (4) the duration of marketing exclusivity for associated products; (5) which products are eligible for follow-on approval; and (6) the degree to which uniformity is achievable between the FD&C Act and the PHSA. This paper recommends the one hundred and eleventh Congress strike a balance between patient safety, incentives for product innovation, price competition, and the need for a flexible, transparent process that capitalizes on FDA's growing expertise with follow-on biologics approvals under Section 505(b)(2) of the FD&C Act.

  15. Aid alignment: a longer term lens on trends in development assistance for health in Uganda.

    Science.gov (United States)

    Stierman, Elizabeth; Ssengooba, Freddie; Bennett, Sara

    2013-02-20

    Over the past decade, development assistance for health (DAH) in Uganda has increased dramatically, surpassing the government's own expenditures on health. Yet primary health care and other priorities identified in Uganda's health sector strategic plan remain underfunded. Using data available from the Creditor Reporting System (CRS), National Health Accounts (NHA), and government financial reports, we examined trends in how donors channel DAH and the extent to which DAH is aligned with sector priorities. The study follows the flow of DAH from the donor to the implementing organization, specifying the modality used for disbursing funds and categorizing funds based on program area or support function. Despite efforts to improve alignment through the formation of a sector-wide approach (SWAp) for health in 1999 and the creation of a fund to pool resources for identified priorities, increasingly DAH is provided as short-term, project-based support for disease-specific initiatives, in particular HIV/AIDS. These findings highlight the need to better align external resources with country priorities and refocus attention on longer-term sector-wide objectives.

  16. Longer-Term Mental and Behavioral Health Effects of the Deepwater Horizon Gulf Oil Spill

    Directory of Open Access Journals (Sweden)

    Tonya Cross Hansel

    2015-10-01

    Full Text Available Mental health issues are a significant concern after technological disasters such as the 2010 Gulf Oil Spill; however, there is limited knowledge about the long-term effects of oil spills. The study was part of a larger research effort to improve understanding of the mental and behavioral health effects of the Deepwater Horizon Gulf Oil Spill. Data were collected immediately following the spill and the same individuals were resampled again after the second anniversary (n = 314. The results show that mental health symptoms of depression, serious mental illness and posttraumatic stress have not statistically decreased, and anxiety symptoms were statistically equivalent to immediate symptoms. Results also showed that the greatest effect on anxiety is related to the extent of disruption to participants’ lives, work, family, and social engagement. This study supports lessons learned following the Exxon Valdez spill suggesting that mental health effects are long term and recovery is slow. Elevated symptoms indicate the continued need for mental health services, especially for individuals with high levels of disruption resulting in increased anxiety. Findings also suggest that the longer-term recovery trajectories following the Deepwater Horizon Gulf Oil Spill do not fall within traditional disaster recovery timelines.

  17. An exploration of the longer-term impacts of community participation in rural health services design.

    Science.gov (United States)

    Farmer, Jane; Currie, Margaret; Kenny, Amanda; Munoz, Sarah-Anne

    2015-09-01

    This article explores what happened, over the longer term, after a community participation exercise to design future rural service delivery models, and considers perceptions of why more follow-up actions did or did not happen. The study, which took place in 2014, revisits three Scottish communities that engaged in a community participation research method (2008-2010) intended to design rural health services. Interviews were conducted with 22 citizens, healthcare practitioners, managers and policymakers all of whom were involved in, or knew about, the original project. Only one direct sustained service change was found - introduction of a volunteer first responder scheme in one community. Sustained changes in knowledge were found. The Health Authority that part-funded development of the community participation method, through the original project, had not adopted the new method. Community members tended to attribute lack of further impact to low participation and methods insufficiently attuned to the social nuances of very small rural communities. Managers tended to blame insufficient embedding in the healthcare system and issues around power over service change and budgets. In the absence of convincing formal community governance mechanisms for health issues, rural health practitioners tended to act as conduits between citizens and the Health Authority. The study provides new knowledge about what happens after community participation and highlights a need for more exploration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Mammographic breast density in recent and longer-standing ethiopian immigrants to israel.

    Science.gov (United States)

    Sklair-Levy, Miri; Segev, Anat; Sella, Tamar; Calderon-Margalit, Ronit; Zippel, Douglas

    2018-04-23

    High breast density is associated with an increased risk of breast cancer development. Little is known concerning ethnic variations in breast density and its relevant contributing factors. We aimed to study breast density among Ethiopian immigrants to Israel in comparison with Israeli-born women and to determine any effect on breast density of the length of residency in the immigrant population. Mammographic breast density using the BI-RADS system was estimated and compared between 77 women of Ethiopian origin who live in Israel and 177 Israeli-born controls. Logistic regression analysis was performed to estimate the odds ratios (OR) for high density (BI-RADS score ≥ 3) vs low density (BI-RADS score density compared with Israeli-born women. Adjustments for various cofounders did not affect the results. Time since immigration to Israel seemed to modify the relationship, with a stronger association for women who immigrated within 2 years prior to mammography (OR:0.07, 95% CI: 0.03-0.17) as opposed to women with a longer residency stay in Israel (OR:0.23, 95% CI:0.10-0.50). Adjustments of various confounders did not alter these findings. Breast density in Ethiopian immigrants to Israel is significantly lower than that of Israeli-born controls. Our study suggests a positive association between time since immigration and breast density. Future studies are required to define the possible effects of dietary change on mammographic density following immigration. © 2018 Wiley Periodicals, Inc.

  19. News from the Library: Microsoft products no longer on sale at the Bookshop

    CERN Multimedia

    CERN Library

    2013-01-01

    As you might know, for some time the Bookshop also acted as a point of sale of Microsoft products. Please note that this is no longer the case.   The Swiss distributor of Microsoft software - DirAction AG - provides a website where CERN users can acquire copies of Microsoft software for home use. This website is available in three languages - English, French and German - and accepts payments by credit card or by money transfer from a bank account or PayPal. Should you have any problems or questions relating to this website, you can contact the DirAction Team directly at + 41 43 299 44 00 or using the contact form. Note that the CERN Service Desk will not be able to assist you as this is a service provided by DirAction rather than CERN IT. Please refer to this website for complete information on how to purchase Microsoft products. Your feedback is welcome! Please contact us by e-mail.

  20. Karyotypic changes through dysploidy persist longer over evolutionary time than polyploid changes.

    Directory of Open Access Journals (Sweden)

    Marcial Escudero

    Full Text Available Chromosome evolution has been demonstrated to have profound effects on diversification rates and speciation in angiosperms. While polyploidy has predated some major radiations in plants, it has also been related to decreased diversification rates. There has been comparatively little attention to the evolutionary role of gains and losses of single chromosomes, which may or not entail changes in the DNA content (then called aneuploidy or dysploidy, respectively. In this study we investigate the role of chromosome number transitions and of possible associated genome size changes in angiosperm evolution. We model the tempo and mode of chromosome number evolution and its possible correlation with patterns of cladogenesis in 15 angiosperm clades. Inferred polyploid transitions are distributed more frequently towards recent times than single chromosome gains and losses. This is likely because the latter events do not entail changes in DNA content and are probably due to fission or fusion events (dysploidy, as revealed by an analysis of the relationship between genome size and chromosome number. Our results support the general pattern that recently originated polyploids fail to persist, and suggest that dysploidy may have comparatively longer-term persistence than polyploidy. Changes in chromosome number associated with dysploidy were typically observed across the phylogenies based on a chi-square analysis, consistent with these changes being neutral with respect to diversification.

  1. Network survivability performance (computer diskette)

    Science.gov (United States)

    1993-11-01

    File characteristics: Data file; 1 file. Physical description: 1 computer diskette; 3 1/2 in.; high density; 2.0MB. System requirements: Mac; Word. This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunication networks to user expectations for network survivability.

  2. Regulation of Reentrainment Function Is Dependent on a Certain Minimal Number of Intact Functional ipRGCs in rd Mice

    Directory of Open Access Journals (Sweden)

    Jingxue Zhang

    2017-01-01

    Full Text Available Purpose. To investigate the effect of partial ablation of melanopsin-containing retinal ganglion cells (mcRGCs on nonimage-forming (NIF visual functions in rd mice lacking rods. Methods. The rd mice were intravitreally injected with different doses (100 ng/μl, 200 ng/μl, and 400 ng/μl of immunotoxin melanopsin-SAP. And then, the density of ipRGCs was examined. After establishing the animal models with different degrees of ipRGC damage, a wheel-running system was used to evaluate their reentrainment response. Results. Intravitreal injection of melanopsin-SAP led to partial ablation of ipRGCs in a dose-dependent manner. The survival rates of ipRGCs in the 100 ng/μl, 200 ng/μl, and 400 ng/μl groups were 74.14% ± 4.15%, 39.25% ± 2.29%, and 38.38% ± 3.74%, respectively. The wheel-running experiments showed that more severe ipRGC loss was associated with a longer time needed for reentrainment. When the light/dark cycle was delayed by 8 h, the rd mice in the PBS control group took 4.67 ± 0.79 days to complete the synchronization with the shifted cycle, while those in the 100 ng/μl and 200 ng/μl groups required 7.90 ± 0.55 days and 11.00 ± 0.79 days to complete the synchronization with the new light/dark cycle, respectively. Conclusion. Our study indicates that the regulation of some NIF visual functions is dependent on a certain minimal number of intact functional ipRGCs.

  3. Depression and Liver Transplant Survival.

    Science.gov (United States)

    Meller, William; Welle, Nicole; Sutley, Kristen; Thurber, Steven

    Patients who underwent liver transplantation and experienced clinical depression have heretofore evinced lower survival rates when compared to nondepressed counterparts. To investigate the hypothesis that transplant patients who seek and obtain medical treatment for depression would circumvent the prior reduced survival findings. A total of 765 patients with liver transplants were scrutinized for complications following transplantation. Further, 104 patients experienced posttransplant depression as manifested by diagnosis and treatment by medical personnel. Survival analyses were conducted comparing hazard and survival curves for these selected individuals and the remainder of transplant patients. Contrary to prior data and consistent with the aforementioned hypothesis, median survival durations, survival curves, and hazard functions (controlling for age and prolonged posttransplant survival for the depressed patients were better. The improved survival for the depressed patients may simply be related to an amelioration of depressed symptoms via antidepressant medications. However, this interpretation would only be congruent with reduced hazard, not elevated survival, beyond the norm (median) for other transplant participants. Assuming the reliability and generalization of our findings, perhaps a reasonable and compelling interpretation is that combined with the effectiveness of antidepressant medications, the seeking and receiving treatment for depression is a type of proxy measure of a more global pattern of adherence to recommended posttransplant medical regimens. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  4. Ship Systems Survivability Test Site

    Data.gov (United States)

    Federal Laboratory Consortium — Area for testing survivability of shipboard systems to include electrical, communications, and fire suppression. Multipurpose test range for supporting gun firing,...

  5. Cell survival in a simulated Mars environment

    Science.gov (United States)

    Todd, Paul; Kurk, Michael Andy; Boland, Eugene; Thomas, David

    2016-07-01

    were introduced on the first day (less than 1 hour). All Samples were mixed into Mars regolith simulant for this test. Biological samples consisting of Cyanobacteria: Anabena sp., Chroococcidiopsis CCMEE171, Plectonema boryanum; Eubacteria: Bacillus subtilis, Pseudomonas aeruginosa, and Eukaryota: Chlorella ellipsoidia were maintained in the simulator under the above-described conditions. The exposed specimens were tested for intracellular esterase activity (fluorescein diacetate (FDA) hydrolysis), chlorophyll content (where appropriate) and reproductive survival (colony formation on nutrient plates). These tests all yielded low-level positive results indicating some survival in all cases. Three control populations of each species were simultaneously exposed to -80 C dark storage, +4 C dark storage, and +25 C diurnal cycles in the same Mars regolith simulant (Orbital Technologies, Madison, WI). The survival hierarchy based on intracellular esterase assay, in decreasing order of survival was Anabena > Chroococcidiopsis > Pseudomonas > Bacillus subtilis > Chlorella > Plectonema, and the range of survival based on this test was 8% - 50%. The survival hierarchy based on post-exposure colony growth was Plectonema > Chroococcidiopsis = Chlorella > Anabena, and Pseudomonas exhibited higher survival than Bacillus subtilis. These results indicate a need for longer-term high-fidelity planetary simulation studies of a wider variety of microbial species including extremophiles, such as psychrophilic strains like Psychrobacter spp., Planococcus halocryophilus, Rhodococcus sp. and the yeast Rhodotorula sp. that could be found in human environments. This research was supported by NASA NIAC Phase I Grant "Mars Ecopoiesis Testbed" NNX14AM97G.

  6. Surviving a Suicide Attempt

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Harrasi

    2016-09-01

    Full Text Available Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors and protective factors (like religious affiliation and family support. All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor.

  7. Survival and weak chaos.

    Science.gov (United States)

    Nee, Sean

    2018-05-01

    Survival analysis in biology and reliability theory in engineering concern the dynamical functioning of bio/electro/mechanical units. Here we incorporate effects of chaotic dynamics into the classical theory. Dynamical systems theory now distinguishes strong and weak chaos. Strong chaos generates Type II survivorship curves entirely as a result of the internal operation of the system, without any age-independent, external, random forces of mortality. Weak chaos exhibits (a) intermittency and (b) Type III survivorship, defined as a decreasing per capita mortality rate: engineering explicitly defines this pattern of decreasing hazard as 'infant mortality'. Weak chaos generates two phenomena from the normal functioning of the same system. First, infant mortality- sensu engineering-without any external explanatory factors, such as manufacturing defects, which is followed by increased average longevity of survivors. Second, sudden failure of units during their normal period of operation, before the onset of age-dependent mortality arising from senescence. The relevance of these phenomena encompasses, for example: no-fault-found failure of electronic devices; high rates of human early spontaneous miscarriage/abortion; runaway pacemakers; sudden cardiac death in young adults; bipolar disorder; and epilepsy.

  8. A survival programme

    International Nuclear Information System (INIS)

    Vester, F.

    1978-01-01

    The book is a non-speculative information source on ecological problems and their possible solutions. It is a 'programme' from a twofold point of view: it determines political and scientific-technological objectives and it transfers knowledge by mental steps with techniques of programmed instruction. Thus emphasis is laid on detailed problems, especially by conscionsly challenged redundancies, and, on the other hand, a greater context is presented. Selected facts are examined under their different aspects, interactions and control circuits are described. Each chapter will speak for itself after the introduction has been read but is related to other chapters by cross references, illustrative material, a glossary and a comprehensive list of references. The 'Survival Programme' is a realistic and challenging discussion with the problem of 'Ecology in the Industrial Age'. It adresses scientists from various disciplines but also offers itself as a compendium to laymen in search of information, members of citizens initiatives and responsible representants of the political and industrial world. (orig./HP) [de

  9. VSVΔG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

    Science.gov (United States)

    Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

    2015-02-01

    Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSVΔG/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSVΔG/EBOV GP treatment. In the current study, an in vivo mouse model of the VSVΔG/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSVΔG/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSVΔG/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-γ secretion was significantly higher with VSVΔG/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSVΔG/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-γ secretion.

  10. Humans and mice express similar olfactory preferences.

    Directory of Open Access Journals (Sweden)

    Nathalie Mandairon

    Full Text Available In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.

  11. Do benefits accrue from longer rotations for students in Rural Clinical Schools?

    Science.gov (United States)

    Denz-Penhey, Harriet; Shannon, Susan; Murdoch, Campbell J; Newbury, Jonathon W

    2005-01-01

    areas of need. Clinical benefits: contributions to the clinical team: students in their clinical years want to feel useful and to be allowed to become contributors to the medical care, even as they are learning. A longer rotation allows them to become known to their teachers who are then able to easily assess the type of contribution that is appropriate for their students to undertake. Students then become full participating members of the healthcare team, rather than observing learners. Social benefits: all students with a home base actively participated in a wide range of community activities outside their role as medical students. Those students undertaking short rotations without a home base seldom connected in the same way to any rural community. Evaluation from these two RCS has shown that short rotations are likely to be less optimal than longer rotations for meeting the broader goals of the RCS to build future workforce capacity. Our results suggest that one opportunity to acculturate students into the rural lifestyle is lost when students' placements are insufficiently long for them to put down roots in their community, and to understand how to 'live' there more broadly. Good rural experiences and teaching and learning opportunities are not sufficient in themselves. Students' emotional attachment to rural living comes from experience related to time and the connection to local people that comes as a result of time spent in the community. Students on short rotations do not make that local connection.

  12. Ethnographic Study at a Music Library Found Students Prefer Short Stopovers and Longer Solitary Study

    Directory of Open Access Journals (Sweden)

    Dominique Daniel

    2014-04-01

    technology. According to data from the flip books, 44% engaged in multitasking, which was therefore significant but not preferred. It was more likely to occur when electronic technology was involved. Patrons were most likely to be present in the library for less than 5 minutes or more than 20 minutes. Patrons who stayed in the library for only a short time were more likely to engage in leisure activities than those who stayed longer, but leisure activities overall were as prevalent as study time. The technology lab and the reference area were the most popular zones. Users stayed in the technology lab and stacks for short times only, whereas the reference area and carrels were favored for long visits. Users engaged in multitasking mostly in the carrels and reference area. Conclusion – The patrons’ preference for solitary study is at odds with academic libraries’ current interest in collaborative learning spaces, but can be explained by the specific nature of music studies (artistic creation is a solitary activity, and is in line with previous ethnographic studies of public libraries. Music students presumably use the technology labs for short visits between classes. They favor the study carrels for longer stays where they can multitask, using their own laptops and iPods. These findings can be used to help redesign the library. Design recommendations include placing the technology lab by the entrance to enable quick coming and going, increasing the number of carrels, placing them in quiet parts of the library, and equipping them with electrical outlets.

  13. Temporal event structure and timing in schizophrenia: preserved binding in a longer "now".

    Science.gov (United States)

    Martin, Brice; Giersch, Anne; Huron, Caroline; van Wassenhove, Virginie

    2013-01-01

    Patients with schizophrenia experience a loss of temporal continuity or subjective fragmentation along the temporal dimension. Here, we develop the hypothesis that impaired temporal awareness results from a perturbed structuring of events in time-i.e., canonical neural dynamics. To address this, 26 patients and their matched controls took part in two psychophysical studies using desynchronized audiovisual speech. Two tasks were used and compared: first, an identification task testing for multisensory binding impairments in which participants reported what they heard while looking at a speaker's face; in a second task, we tested the perceived simultaneity of the same audiovisual speech stimuli. In both tasks, we used McGurk fusion and combination that are classic ecologically valid multisensory illusions. First, and contrary to previous reports, our results show that patients do not significantly differ from controls in their rate of illusory reports. Second, the illusory reports of patients in the identification task were more sensitive to audiovisual speech desynchronies than those of controls. Third, and surprisingly, patients considered audiovisual speech to be synchronized for longer delays than controls. As such, the temporal tolerance profile observed in a temporal judgement task was less of a predictor for sensory binding in schizophrenia than for that obtained in controls. We interpret our results as an impairment of temporal event structuring in schizophrenia which does not specifically affect sensory binding operations but rather, the explicit access to timing information associated here with audiovisual speech processing. Our findings are discussed in the context of curent neurophysiological frameworks for the binding and the structuring of sensory events in time. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Longer guts and higher food quality increase energy intake in migratory swans.

    Science.gov (United States)

    van Gils, Jan A; Beekman, Jan H; Coehoorn, Pieter; Corporaal, Els; Dekkers, Ten; Klaassen, Marcel; van Kraaij, Rik; de Leeuw, Rinze; de Vries, Peter P

    2008-11-01

    1. Within the broad field of optimal foraging, it is increasingly acknowledged that animals often face digestive constraints rather than constraints on rates of food collection. This therefore calls for a formalization of how animals could optimize food absorption rates. 2. Here we generate predictions from a simple graphical optimal digestion model for foragers that aim to maximize their (true) metabolizable food intake over total time (i.e. including nonforaging bouts) under a digestive constraint. 3. The model predicts that such foragers should maintain a constant food retention time, even if gut length or food quality changes. For phenotypically flexible foragers, which are able to change the size of their digestive machinery, this means that an increase in gut length should go hand in hand with an increase in gross intake rate. It also means that better quality food should be digested more efficiently. 4. These latter two predictions are tested in a large avian long-distance migrant, the Bewick's swan (Cygnus columbianus bewickii), feeding on grasslands in its Dutch wintering quarters. 5. Throughout winter, free-ranging Bewick's swans, growing a longer gut and experiencing improved food quality, increased their gross intake rate (i.e. bite rate) and showed a higher digestive efficiency. These responses were in accordance with the model and suggest maintenance of a constant food retention time. 6. These changes doubled the birds' absorption rate. Had only food quality changed (and not gut length), then absorption rate would have increased by only 67%; absorption rate would have increased by only 17% had only gut length changed (and not food quality). 7. The prediction that gross intake rate should go up with gut length parallels the mechanism included in some proximate models of foraging that feeding motivation scales inversely to gut fullness. We plea for a tighter integration between ultimate and proximate foraging models.

  15. Longer and less overlapping food webs in anthropogenically disturbed marine ecosystems: confirmations from the past.

    Directory of Open Access Journals (Sweden)

    Fabiana Saporiti

    Full Text Available The human exploitation of marine resources is characterised by the preferential removal of the largest species. Although this is expected to modify the structure of food webs, we have a relatively poor understanding of the potential consequences of such alteration. Here, we take advantage of a collection of ancient consumer tissues, using stable isotope analysis and SIBER to assess changes in the structure of coastal marine food webs in the South-western Atlantic through the second half of the Holocene as a result of the sequential exploitation of marine resources by hunter-gatherers, western sealers and modern fishermen. Samples were collected from shell middens and museums. Shells of both modern and archaeological intertidal herbivorous molluscs were used to reconstruct changes in the stable isotopic baseline, while modern and archaeological bones of the South American sea lion Otaria flavescens, South American fur seal Arctocephalus australis and Magellanic penguin Spheniscus magellanicus were used to analyse changes in the structure of the community of top predators. We found that ancient food webs were shorter, more redundant and more overlapping than current ones, both in northern-central Patagonia and southern Patagonia. These surprising results may be best explained by the huge impact of western sealing on pinnipeds during the fur trade period, rather than the impact of fishing on fish populations. As a consequence, the populations of pinnipeds at the end of the sealing period were likely well below the ecosystem's carrying capacity, which resulted in a release of intraspecific competition and a shift towards larger and higher trophic level prey. This in turn led to longer and less overlapping food webs.

  16. Dissemination of English Culture in Chinua Achebe’s No Longer at Ease

    Directory of Open Access Journals (Sweden)

    Bahman Zarrinjooee

    2016-08-01

    Full Text Available This paper deals with Chinua Achebe’s (1930-2013 No Longer at Ease (1960 which depicts the dissemination of English culture in Nigeria and its effects on the life and identity of Obi Okonkwo, the Western educated male protagonist. The focus of this paper is on the dissemination of English culture and submission of Nigerian culture in order to represent the inferiority of Nigerians. Edward Said’s (1935-2003 attempts regarding Orientalism and Frantz Fanon’s (1925-1961 issues relating inferiority of the indigenous people caused by colonization are used in this paper. The colonisers affect the life, mind, culture, and identity of the colonized through various ways such as education, religion, and language. Such effects cause some cultural transformation and changes in language of the colonized people. Moreover, the colonizer through stereotyping the colonized people assumes them as other. Indeed, the colonizer imposes his/her superiority on the natives who try to assimilate themselves with the colonizer. Achebe in his novel shows how this effort causes some binary relation among the characters. The novel shows the difference between two cultures, and Achebe puts emphasis on the superiority of English culture and depicts how colonialism and Western orientalism produce stereotyped images of Nigerians and Obi as corrupt. Consequently, such features have great impressions on the mind of Nigerians, which results in inferiority complex. Such characteristic invites the Nigerians to follow European’s value and forget their own culture, which is resulted in the rejection of native values. Keywords: Binary Relation, Colonization, Cultural Transformation, Cultural Dissemination, Orientalism, Stereotyping

  17. Longer Duration of Urinary Catheterization Increases Catheter-Associated Urinary Tract Infection in PICU.

    Science.gov (United States)

    Fukuoka, Kahoru; Furuichi, Mihoko; Ito, Kenta; Morikawa, Yoshihiko; Watanabe, Ichiro; Shimizu, Naoki; Horikoshi, Yuho

    2018-06-13

    Catheter-associated urinary tract infections account for 30% of healthcare-associated infections. To date, few studies have addressed pediatric catheter-associated urinary tract infection in PICUs. The aim of our study was to assess the risk of catheter-associated urinary tract infection in relation to the duration of catheterization in the PICU. Retrospective cohort study. PICU at a tertiary children's hospital. Our study was conducted between April 2012 and June 2015 at Tokyo Metropolitan Children's Medical Center in Japan. Children in the PICU with an urethral catheter were included. Catheter-associated urinary tract infection cases were defined according to the National Healthcare Safety Network criteria. The patients' demographic data and isolated organisms were reviewed. Duration of catheterization and the catheter-associated urinary tract infection occurrence rate were analyzed. None. Among 1,890 catheterizations, 23 catheter-associated urinary tract infection cases were identified. The overall occurrence rate was 2.35/1,000 catheter-days. Among the patients with catheter-associated urinary tract infection, 13 were boys. The median age was 11 months (interquartile range, 7-35 mo), and the median duration of catheterization was 7 days (interquartile range, 5-12 d). The isolated bacteria were Escherichia coli (26.5%), Enterococcus faecalis (17.6%), and Klebsiella pneumoniae (11.8%). Two species were isolated in each of 11 cases (47.8%). Each additional day of catheterization increased the risk of catheter-associated urinary tract infection (odds ratio, 1.06; 95% CI, 1.02-1.10, and odds ratio adjusted for contact precaution status and surgical procedures was 1.05; 95% CI, 1.01-1.09). Longer duration of catheterization increased the risk of catheter-associated urinary tract infection by 5% each day at the PICU. Prompt removal of the urethral catheter is strongly recommended whenever feasible.

  18. The self-management of longer-term depression: learning from the patient, a qualitative study.

    Science.gov (United States)

    Chambers, Eleni; Cook, Sarah; Thake, Anna; Foster, Alexis; Shaw, Sue; Hutten, Rebecca; Parry, Glenys; Ricketts, Tom

    2015-07-24

    Depression is a common mental health condition now viewed as chronic or long-term. More than 50 % of people will have at least one further episode of depression after their first, and therefore it requires long-term management. However, little is known about the effectiveness of self-management in depression, in particular from the patients' perspective. This study aimed to understand how people with longer-term depression manage the condition, how services can best support self-management and whether the principles and concepts of the recovery approach would be advantageous. Semi-structured in depth interviews were carried out with 21 participants, recruited from a range of sources using maximum variation sampling. Interpretative Phenomenological Analysis was used by a diverse team comprised of service users, practitioners and academics. Four super-ordinate themes were found: experience of depression, the self, the wider environment, self-management strategies. Within these, several prominent sub-themes emerged of importance to the participants. These included how aspects of themselves such as hope, confidence and motivation could be powerful agents; and how engaging in a wide range of chosen activities could contribute to their emotional, mental, physical, social, spiritual and creative wellbeing. Services in general were not perceived to be useful in specifically facilitating self-management. Increased choice and control were needed and a greater emphasis on an individualised holistic model. Improved information was needed about how to develop strategies and locate resources, especially during the first episode of depression. These concepts echoed those of the recovery approach, which could therefore be seen as valuable in aiding the self-management of depression.

  19. Pediatric Systemic Lupus Erythematosus: Learning From Longer Follow Up to Adulthood

    Directory of Open Access Journals (Sweden)

    Giorgio Costagliola

    2018-05-01

    Full Text Available Background: Pediatric systemic lupus erythematosus (pSLE is a rare condition, representing approximately 10% of SLE cases. The aim of this study was to identify variables to improve the diagnostic awareness and management of pSLE patients.Methods: This retrospective study included 25 patients diagnosed with pSLE and followed at the University of Pisa. We collected data about clinical profile at disease onset and during a long-term follow-up, including disease activity, organ damage development, and treatments received.Results: The mean patient age at disease onset was 14.6 ± 1.6 years, and the mean follow-up period was 14.17 ± 8.04 years. The most common initial manifestations were arthritis, malar rash, and cytopenias. The median time to diagnosis since the first symptoms was 6 months, and was significantly longer in patients with hematological onset (54 months. During follow-up, the number of patients with renal involvement showed a significant increase, from 36% at diagnosis to 72.2% after 10 years of disease evolution. Patients who developed chronic organ damage maintained a higher time-averaged disease activity during follow-up and received a significantly higher dose of corticosteroids.Conclusion: Patients with immune cytopenia represent a group deserving strict clinical follow-up for the risk of evolution to SLE. Intense surveillance of renal function, early treatment and steroid-sparing strategies should be strongly considered in the management of pSLE patients.

  20. LONGER-TERM EFFECTIVENESS OF CBT IN TREATMENT OF COMORBID AUD/MDD ADOLESCENTS.

    Science.gov (United States)

    Cornelius, Jack R; Douaihy, Antoine B; Kirisci, Levent; Daley, Dennis C

    2013-01-01

    Cognitive Behavioral Therapy (CBT) is a commonly used therapy among persons with major depressive disorder (MDD) and also among those with alcohol use disorders (AUD). However, less is known regarding the efficacy of CBT for treating persons with co-occurring disorders involving both MDD and an AUD. Studies assessing the efficacy of CBT in adolescent populations with co-occurring disorders are particularly sparse, especially studies designed to assess the potential longer-term efficacy of an acute phase trial of CBT therapy in that youthful comorbid population. We recently conducted a first acute phase treatment study involving comorbid AUD/MDD adolescents, which involved the medication fluoxetine as well as manualized CBT therapy. The results of that acute phase study suggested efficacy for CBT therapy but not for fluoxetine for treating the depressive symptoms and the excessive alcohol use of study subjects (Cornelius et al., 2009). The current chapter provides an assessment of the long-term efficacy of CBT for treating comorbid AUD/MDD adolescents, based on results from our own long-term (four-year) follow-up study, which was conducted following the completion of our recent acute phase treatment study. The results of the study suggest long-term efficacy for acute phase CBT/MET therapy for treating both the depressive symptoms and the excessive alcohol use of comorbid AUD/MDD adolescents, but demonstrate no evidence of long-term efficacy for fluoxetine for treating either the depressive symptoms or the excessive alcohol use of that population.

  1. Improved sonothrombolysis from a modified diagnostic transducer delivering impulses containing a longer pulse duration.

    Science.gov (United States)

    Wu, Juefei; Xie, Feng; Kumar, Tanmay; Liu, Jinjin; Lof, John; Shi, William; Everbach, E Carr; Porter, Thomas R

    2014-07-01

    Although guided high-mechanical-index (MI) impulses from a diagnostic ultrasound transducer have been used in preclinical studies to dissolve coronary arterial and microvascular thrombi in the presence of intravenously infused microbubbles, it is possible that pulse durations (PDs) longer than that used for diagnostic imaging may further improve the effectiveness of this approach. By use of an established in vitro model flow system, a total of 90 occlusive porcine arterial thrombi (thrombus age: 3-4 h) within a vascular mimicking system were randomized to 10-min treatments with two different PDs (5 and 20 μs) using a Philips S5-1 transducer (1.6-MHz center frequency) at a range of MIs (from 0.2 to 1.4). All impulses were delivered in an intermittent fashion to permit microbubble replenishment within the thrombosed vessel. Diluted lipid-encapsulated microbubbles (0.5% Definity) were infused during the entire treatment period. A tissue-mimicking phantom 5 cm thick was placed between the transducer and thrombosed vessel to mimic transthoracic attenuation. Two 20-MHz passive cavitation detection systems were placed confocal to the insonified vessel to assess for inertial cavitational activity. Percentage thrombus dissolution was calculated by weighing the thrombi before and after each treatment. Percentage thrombus dissolution was significantly higher with a 20-μs PD already at the 0.2 and 0.4 MI therapeutic impulses (54 ± 12% vs. 33 ± 17% and 54 ± 22% vs. 34 ± 17%, p cavitation detection systems detected only low intensities of inertial cavitation. At higher MI settings and 20-μs PDs, percentage thrombus dissolution decreased most likely from high-intensity cavitation shielding of the thrombus. Slightly prolonging the PD on a diagnostic transducer improves the degree of sonothrombolysis that can be achieved without fibrinolytic agents at a lower mechanical index. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc

  2. Reduced Acetylcholine Receptor Density, Morphological Remodeling, and Butyrylcholinesterase Activity Can Sustain Muscle Function in Acetylcholinesterase Knockout Mice

    National Research Council Canada - National Science Library

    Adler, Michael; Manley, Heather A; Deshpande, Sharad S; Hamilton, Tracey A; Kan, Robert K; Oyler, George; Lockridge, Oksana; Duysen, Ellen G; Sheridan, Robert E

    2004-01-01

    ...) and can survive into adulthood. Twitch tensions elicited in diaphragms of AChE-/- mice by single supramaximal stimuli had larger amplitudes and slower rise and decay times than did those in wild-type animals...

  3. Protective effect of Asparagus racemosus root extract against lethal total - body electron beam radiation induced damage in Swiss albino mice

    International Nuclear Information System (INIS)

    Sharmila, K.P.; Bhandary, B. Satheesh Kumar; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

    2016-01-01

    To investigate the protective effect of Asparagus Racemosus Root ethanolic extract (ARE) in Swiss albino mice against acute lethal total - body Electron beam irradiation. Swiss Albino mice were used for the assessment of radiation induced sickness and 30 day survival analysis. Survival studies were determined using the Kaplan-Meier survival curves. The maximum survival was observed in the experimental mice pretreated with 200 mg/kg.b.wt. of ARE which also reduced the radiation sickness characteristics. This dose was considered as an optimal dose for radioprotection. Treatment of mice with ARE before irradiation delayed the onset of mortality as compared with the untreated irradiated controls. Present findings demonstrate the potential of ARE in mitigating radiation-induced mortality, which may be attributed to its free radical scavenging and increased antioxidant potential

  4. Lifespan studies on different strains of mice exposed chronically to low levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Fox, L.A.; Klein, A.K.; Cain, G.R.; Rosenblatt, L.S.

    1982-01-01

    Several strains of mice, chosen for their predisposition to immunohematological disorders, were exposed to low levels of 60 irradiation continuously for four weeks. All individuals were subsequently followed throughout their lifetimes. W/W/sup v/ mice, which are tyically subject to a stem cell deficiency, had a lower cumulative survival rate for the irradiated group than for the unirradiated controls. Irradiated RF/sub j/ mice had a dramatically lower cumulative survival rate than their unirradiated controls. Conversely, BXSB mice, which have a lumphoproliferative autoimmune disorder, had a higher cumulative survival rate after chronic irradiation than did unirradiated BXSBs. Irradiation had no effect upon the survival rate curves of the NZB strain, the murine model for Lupus Erythematosus

  5. Crybb2 deficiency impairs fertility in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Qian [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Sun, Li-Li [Aviation Medical Evaluation and Training Center of Airforce in Dalian, Dalian, Liaoning Province 116013 (China); Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Xiang, Fen-Fen [Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062 (China); Gao, Li [Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Zhang, Jun-Jie, E-mail: zhangjj910@163.com [Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Li, Wen-Jie, E-mail: wenjieli@pku.org.cn [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2014-10-10

    Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2{sup −/−}) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2{sup −/−} mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2{sup −/−} mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2{sup −/−} female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2{sup −/−} mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2{sup −/−} mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells.

  6. Crybb2 deficiency impairs fertility in female mice

    International Nuclear Information System (INIS)

    Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

    2014-01-01

    Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2 −/− ) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2 −/− mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2 −/− mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2 −/− female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2 −/− mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2 −/− mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells

  7. Radioprotective effects of dextran sulphate in mice

    International Nuclear Information System (INIS)

    Vacek, A.; Bartonickova, A.; Rotkovska, D.; Palyga, G.F.; Zhukova, N.A.

    1981-01-01

    Influence of a single i.p. injection of dextran sulphate on radiosensitivity of mice was investigated. The administration of dextran sulphate 24, 48 and 72 hours prior to irradiation increased formation of endogenous colonies of the hemopoietic tissue on the surface of the spleen. DRF calculated from an equieffective exposure for 5 colonies was 1.96 when dextran sulphate was administered 24 hours before irradiation, and 2.25 when dextran sulphate was administered 72 hours before irradiation. The radioprotective effects of dextran sulphate were manifested also in the survival of animals exposed to lethal doses of short-termed as well as long-termed gamma radiation. (orig.) [de

  8. Global Activities and Plant Survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2014-01-01

    the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...

  9. Radionuclide blood cell survival studies

    International Nuclear Information System (INIS)

    Bentley, S.A.; Miller, D.T.

    1986-01-01

    Platelet and red cell survival studies are reviewed. The use of 51 Cr and di-isopropylfluoridate labelled with tritium or 32 P is discussed for red cell survival study and 51 Cr and 111 In-oxine are considered as platelet labels. (UK)

  10. Modelling survival: exposure pattern, species sensitivity and uncertainty.

    Science.gov (United States)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B; Van den Brink, Paul J; Veltman, Karin; Vogel, Sören; Zimmer, Elke I; Preuss, Thomas G

    2016-07-06

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

  11. Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

    Directory of Open Access Journals (Sweden)

    Gilly Wolf

    2017-06-01

    Full Text Available Bilateral common carotid artery stenosis (BCAS models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month and young adult (3 month female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014: on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049, while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05 compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01 and old control mice (p < 0.05. These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

  12. Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

    Science.gov (United States)

    Koga, Y; Naraparaju, V R; Yamamoto, N

    1999-01-01

    Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor.

  13. Lower chest compression fraction associated with ROSC in OHCA patients with longer downtimes.

    Science.gov (United States)

    Talikowska, Milena; Tohira, Hideo; Inoue, Madoka; Bailey, Paul; Brink, Deon; Finn, Judith

    2017-07-01

    To investigate the relationship between chest compression fraction (CCF) and survival outcomes in OHCA, including whether the relationship varied based upon downtime from onset of arrest to provision of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS). Data from resuscitations performed by St John Ambulance Western Australia (SJA-WA) paramedics between July 2014 and June 2016 was captured using the Q-CPR feedback device. Logistic regression analysis was used to study the relationship between CCF and return of spontaneous circulation (ROSC). Various lengths of Q-CPR data were used ranging from the first 3min to all available episode data. Cases were subsequently divided into groups based upon downtime; ≤15min, >15min and unknown. Univariate and multivariable logistic regression analyses were performed in each group. There were 341 cases eligible for inclusion. CCF >80% was significantly associated with decreased odds of ROSC compared to CCF≤80% (aOR: 0.49, 95%CI: 0.28-0.87). This relationship remained significant whether the first 3min of data was used, the first 5min or all available episode data. Among the group with a downtime >15min, CCF was significantly lower for those who achieved ROSC compared to those who did not (mean (SD): 73.01 (12.99)% vs. 83.05 (9.38)% p=0.002). The adjusted odds ratio for achieving ROSC in this group was significantly less with CCF>80% compared to CCF≤80% (aOR: 0.06, 95%CI: 0.01-0.38). We demonstrated an inverse relationship between CCF and ROSC that varied depending upon the time from arrest to provision of EMS-CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The longer the better: Sleep-wake patterns during preparation of the World Rowing Junior Championships.

    Science.gov (United States)

    Kölling, Sarah; Steinacker, Jürgen M; Endler, Stefan; Ferrauti, Alexander; Meyer, Tim; Kellmann, Michael

    2016-01-01

    Recovery is essential for high athletic performance, and therefore especially sleep has been identified as a crucial source for physical and psychological well-being. However, due to early-morning trainings, which are general practice in many sports, athletes are likely to experience sleep restrictions. Therefore, this study investigated the sleep-wake patterns of 55 junior national rowers (17.7 ± 0.6 years) via sleep logs and actigraphy during a four-week training camp. Recovery and stress ratings were obtained every morning with the Short Recovery and Stress Scale on a 7-point Likert-type scale ranging from 0 (does not apply at all) to 6 (fully applies). The first training session was scheduled for 6:30 h every day. With two to four training sessions per day, the training load was considerably increased from athletes' home training. Objective sleep measures (n = 14) revealed less total sleep time (TST) in the first two weeks (409.6 ± 19.1 and 416.0 ± 16.3 min), while training volume and intensity were higher. In the second half of the camp, less training sessions were implemented, more afternoons were training free and TSTs were longer (436.3 ± 15.8 and 456.9 ± 25.7 min). A single occasion of 1.5-h delayed bedtime and usual early morning training (6:30 h) resulted in reduced ratings of Overall Recovery (OR) (M = 3.3 ± 1.3) and greater Negative Emotional State (NES) (M = 1.3 ± 1.2, p sleep-offset times were shifted from ~5:30 to ~8:00 h, and each recovery and stress score improved (p sleep and recovery. Intercorrelations of these sleep parameters emphasised the relationship between restful sleep and falling asleep quickly (r = .34, p sleep on subjective recovery measures in the setting of a training camp. Providing the opportunity of extended sleep (and a day off) seems the most simple and effective strategy to enhance recovery and stress-related ratings.

  15. Improving performance management for delivering appropriate care for patients no longer needing acute hospital care.

    Science.gov (United States)

    Penney, Christine; Henry, Effie

    2008-01-01

    The public, providers and policy-makers are interested in a service continuum where care is provided in the appropriate place. Alternate level of care is used to define patients who no longer need acute care but remain in an acute care bed. Our aims were to determine how subacute care and convalescent care should be defined in British Columbia (BC); how these care levels should be aligned with existing legislation to provide more consistent service standards to patients and what reporting requirements were needed for system planning and performance management. A literature review was conducted to understand the international trends in performance management, care delivery models and change management. A Canada-wide survey was carried out to determine the directions of other provinces on the defined issues and a BC survey provided a current state analysis of programming within the five regional health authorities (HAs). A provincial policy framework for subacute and convalescent care has been developed to begin to address the concerns raised and provide a base for performance measurement. The policy has been approved and disseminated to BC HAs for implementation. An implementation plan has been developed and implementation activities have been integrated into the work of existing provincial committees. Evaluation will occur through performance measurement. The benefits anticipated include: clear policy guidance for programme development; improved comparability of performance information for system monitoring, planning and integrity of the national acute care Discharge Abstracting Database; improved efficiency in acute care bed use; and improved equity of access, insurability and quality for patients requiring subacute and convalescent care. While a national reporting system exists for acute care in Canada, this project raises questions about the implications for this system, given the shifting definition of acute care as other care levels emerge. Questions are also

  16. WHEN GROWTH IS NO LONGER THE NORM: TEACHING URBAN DESIGN IN A TIME OF TRANSFORMATION

    Directory of Open Access Journals (Sweden)

    Sujata Shetty

    2010-07-01

    Full Text Available Over the past few years, there has been increasing interest in cities that are rapidly losing population, so-called shrinking cities. This is becoming a global phenomenon, with shrinking cities found o